{"paper_id":"2851aaaf-0804-42e1-82f4-c5ff4694189a","body_text":"Effect of acupuncture in patients with postprandial distress syndrome: a multicentre, single-blind, double-dummy, active-controlled, randomized, clinical trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Effect of acupuncture in patients with postprandial distress syndrome: a multicentre, single-blind, double-dummy, active-controlled, randomized, clinical trial Zhaobo Yan, Xuan Xu, Mai-Lan Liu, Zhimiao Murong, Huan Zhong, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4347152/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction Postprandial distress syndrome (PDS) is the prominent subtype in patients with functional dyspepsia (FD) and currently lacks a satisfactory treatment. Acupuncture has become a promising alternative and complementary therapy for managing FD. However, high-level clinical evidence supporting the use of acupuncture for FD is limited. Methods This study is a multicentre, double-dummy, single-blind, randomized, active-controlled trial. Two hundred and one eligible participants will be randomly assigned into three groups: an acupuncture plus placebo group, an itopride plus sham acupuncture group, and a sham acupuncture plus placebo group. This study consists of a 1-week screening period, a 4-week treatment period, and a 12-week follow-up period. During the intervention period, participants will receive 12 sessions of verum or sham acupuncture treatment (one session per day, three sessions per week, for 4 weeks) along with 50 mg itopride tablets or 50 mg itopride placebo tablets 3 times a day for 20 days (5 continual days a week for 4 weeks). The response rate (patients who had adequate relief of gastric symptoms were considered positive responders) and the elimination rate of cardinal symptoms (postprandial fullness and early satiation) are the primary indicators to evaluate the overall acupuncture effect for PDS. Secondary outcome measures will include the Nepean Dyspepsia Symptom Index (NDSI), the short form-Nepean Dyspepsia Life Quality Index (SF-LQI), and the Hospital Anxiety and Depression Scale (HADS). Participants’ expectations towards acupuncture treatment will also be assessed, and adverse events will be recorded for safety assessment. All analyses will adhere to an intention-to-treat principle. Discussion In conclusion, this trial will determine the efficacy and safety of acupuncture for PDS and provide more high-level evidence to support its application in treating FD. Trial registration Chinese Clinical Trial Registry ChiCTR2300068001. Registered on 2 February 2023. acupuncture clinical trial functional dyspepsia acupuncture therapy Figures Figure 1 Figure 2 Background Functional dyspepsia (FD) is a common functional gastrointestinal disorder characterized by upper abdominal discomfort or pain without an identifiable organic cause [ 1 ]. A recent meta-analysis suggests it impacts 8.4% of adults worldwide [ 2 ]. The Rome IV criteria categorizes FD into three subtypes: epigastric pain syndrome (EPS), postprandial distress syndrome (PDS), and the overlapping form of EPS/PDS [1]. PDS, the most common subtype, presents with meal-related symptoms such as postprandial fullness and early satiety. Epidemiological studies from various countries show that PDS accounts for about 60% of FD cases [ 3 , 4 ] and is more prevalent in Asian populations compared to Western populations[ 5 ]. Although not life-threatening, the chronic and recurrent nature of FD symptoms significantly impacts patients’ psychological well-being, quality of life (QOL), and social functioning [ 6 ]. Furthermore, FD imposes a considerable economic burden, with an average yearly direct cost of $699 per patient in the United States [ 7 ]. Therefore, FD has become a significant public health concern requiring heightened clinical attention and research endeavors. The effective treatment of FD remains an unsolved clinical challenge. FD is recognized as a complex condition with several factors participating in its development, including gastric motility disorder, increased gastric acid secretion, psychosocial disorders, and Helicobacter pylori infection [1,6]. Although drugs such as prokinetic agents, acid suppressants, antidepressants, anti-Helicobacter pylori medications, and mucosal protectants have been officially recommended for the treatment of FD, single-drug therapy may not address all of the underlying pathophysiological mechanisms of FD, leading to limited efficacy [ 8 ]. Additionally, these medications may be limited by side effects [ 9 , 10 ]. Therefore, physicians and patients expect more treatments for FD that are both effective and low-risk. Acupuncture is an important part of traditional Chinese medicine (TCM), boasting a history of thousands of years. Acupuncture has rich experience in preventing and treating digestive system diseases; it can be utilized for improving various digestive symptoms, including stomach pain, bloating, nausea, vomiting, diarrhea, and constipation [ 11 , 12 ]. Currently, the acceptance of acupuncture is increasing gradually worldwide. Multiple meta-analyses revealed that acupuncture is more effective than the single use of prokinetic drugs or sham acupuncture in improving digestive symptoms and quality of life in patients with FD [ 13 , 14 ]. Moreover, another system review found that acupuncture combined with Western medicine has a synergistic effect in the treatment of FD while helping to reduce the relapse rate within 3~6 months after treatment [ 15 ]. Additionally, the evidence has shown that acupuncture can regulate gastrointestinal function by improving gastrointestinal motility and reducing visceral sensitivity, which supports the potential of acupuncture as a therapeutic option for FD [ 16 ]. However, due to limited high-quality evidence (evidence grade B), a recent consensus statement did not endorse acupuncture for FD, highlighting the need for further high-quality RCTs to clarify its therapeutic potential and role in FD management [8]. Previous clinical trials have compared the therapeutic effects of acupuncture with prokinetic agents in patients with FD, revealing acupuncture as a superior way to prokinetic agents [ 17 , 18 ]. However, these studies were open-lable and lacked blinding, potentially allowing patient preferences for acupuncture to influence clinical outcomes. To obtain more high-quality evidence, we design a new randomized trial; this trial will administer different treatments (acupuncture or the drug itopride) in a double-dummy, single-blind design to objectively evaluate the effectiveness and safety of acupuncture for PDS compared to itopride. Methods Study design This clinical study is a multicentre, single-blind, double-dummy, randomised, active-controlled trial that compares the efficacy and safety of acupuncture versus itopride in improving upper abdominal discomfort in patients with PDS. The study protocol has been registered with the Chinese Clinical Trial Registry (ChiCTR2300068001). It adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines (Additional file 1) [ 19 ] as well as the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) checklist (Additional file 2) [ 20 ]. The study flowchart is shown in Figure 1. Study setting and recruitment This clinical trial will be conducted collaboratively by an academic center and three clinical institutions. Researchers from the Hunan University of Chinese Medicine will form an academic center group responsible for experimental design, data analysis and results dissemination. Recruitment, treatment and data collection will occur at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, the Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, and Changsha Hospital of Traditional Chinese Medicine. Recruitment is scheduled to take place at inpatient and outpatient departments in three medical centers, and start in September 2024, with the follow-up assessments of all participants completed by December 2026. Recruitment information will be disseminated through various means such as paper flyers, posters, and social platform like Wechat. Participants interested in this trial will be informed about the purpose and process of the study as well as potential risks and benefits. If the patient decides to participate after understanding this information, they will undergo a clinical screening evaluation conducted by registered TCM practitioners with a minimum of 5 years of clinical experience. Eligible patients will sign an informed consent form, receive baseline assessment, and be randomly assigned. Eligibility criteria Inclusion criteria ： The study will involve individuals who meet the following criteria: Aged 18-60 years and long-term residents of Changsha. Diagnosed with FD-PDS according to the Rome IV criteria. No structural abnormalities were detected through upper gastrointestinal endoscopy surveillance. Non-refractory FD. Patients who are helicobacter pylori-negative or have persistent symptoms after helicobacter pylori eradication for one month. Good compliance. Exclusion criteria ： The following individuals will be excluded from the study: Use drugs, such as prokinetics, acid suppression, mucosal protectants, or other FD-related agents, within 2 weeks. Do not tolerate acupuncture. Receive acupuncture treatment within 2 weeks. Have gastrointestinal diseases other than PDS. Pregnant or lactating women and those attempting conception. Patients who are participating in other clinical trials. Diagnosed with malignancy or other serious conditions, such as severe heart, liver, lung, or kidney dysfunction, severe autoimmune disease, or endocrine diseases. Unable to effectively communicate for any reason, such as severe mental illness, cognitive impairment, or impaired language comprehension. Dropout exclusion criteria ： Patients who discontinue treatment due to any of the following reasons (including but not limited to) will be a dropout case： Voluntary withdrawal by participants for any personal reasons. The patient’s symptoms don’t improve and gradually worsened after treatment. Patients are unreachable due to relocated or changed contact information. Patients undergo changes in health status that need a timely manner. Patients experience intolerable side effects and are unwilling to continue treatment. Exit/termination criteria : Patients do not meet the inclusion criteria and are enrolled mistakenly. Patients receive other or additional FD treatments during the study period. Strategies to improve adherence to interventions In order to mitigate the impact of dropout rates on research quality, we will enhance participant compliance through several strategies: Researchers will regularly contact with participants via WeChat or phone calls to understand their condition and remind them about the schedule of their next visit. We will schedule treatment and evaluation sessions at convenient times to minimize disrupting participants' work and daily lives. The evaluation process will be simplified to enhance patient engagement. Participants will be reimbursed for treatment expenses and transportation costs to and from the hospital. Dedicated staff will be available to address any study-related inquiries raised by participants. Randomization, allocation, and concealment A research assistant at each clinical center will conduct random assignments independently from other study activities. Eligible patients will be randomly assigned into the acupuncture plus placebo group, itopride plus sham acupuncture group, and sham acupuncture plus placebo group in a 1:1:1 ratio. A professional statistician will utilize SAS software (v9.3) to produce a list of random numbers stratified by clinical institution using block sizes of 6 or 9. The randomization process will be carried out through an online central randomization system. The randomization number and group assignment provided to each patient by the randomization system will be unique and unchangeable, ensuring fairness in treatment allocation. Blinding This study will maintain blinding among patients, observers, and statisticians. However, acupuncturists will not be blinded due to the nature of the acupuncture procedure. Patients will be informed that the study involves two types of acupuncture treatment and two types of drug, which theoretically can improve PDS symptoms. Regardless of their assigned group, patients will receive a combination treatment comprising one type of acupuncture treatment and one type of drug. Sham acupuncture will be performed by superficial needling on non-acupoints to mimic the verum acupuncture treatment successfully. Itopride placebo tablets will be indistinguishable from verum itopride tablets in taste and appearance. Each patient will undergo treatment in separate rooms to prevent communication between them. Acupuncturists, who will not be blinded, must refrain from discussing assignment information with participants. In the case the trial goes well, the research center will perform unblinding once the statistical analysis is complete. However, if any emergencies arise, such as life-threatening adverse events (AEs), the acupuncturists will perform urgent unblinding. The monitoring team and ethics committee will then analyze the relationship between patient intervention strategies and AEs. Intervention This trial consists of a screening phase (1 week), a treatment phase (4 weeks), and a post-treatment follow-up phase (12 weeks). During the treatment period, participants in the acupuncture plus placebo group will receive 12 sessions of verum acupuncture treatment and itopride placebo tablets for 20 days. Patients in the itopride plus sham acupuncture group will take itopride tablets for 20 days and receive 12 sessions of sham acupuncture treatment. Patients in the placebo plus sham acupuncture group will take itopride placebo tablets for 20 days and receive 12 sessions of sham acupuncture treatment. The detailed treatment procedures is as follows: Verum or sham acupuncture Participants in the acupuncture plus itopride group will receive verum acupuncture at 5 specific acupoints: SiBai (ST2), Liangmen (ST21), Zusanli (ST36), Neiguan (PC6), and Gongsun (SP4). This acupoint protocol is based on our prior clinical research on acupuncture for FD. The location of all acupoints is illustrated in Figure 2 and detailed in Table 1, following the Nomenclature and location of acupuncture points per the Chinese National Standard (GB/T22163-2008). Patients will be supine and maintain mental relaxation as per practitioner instruction. Acupuncturists will sterilize both the needle (Huatuo brand, Suzhou Medical Supplies Factory, China) and the skin at the acupoint locations before insertion. The depth of needle penetration will vary depending on the acupoints, refer to Table 1 for details. After the needles penetrate the skin, acupuncturists will manipulated them with lifting, inserting, or twisting movements until patients feel the Deqi sensation. The needles will be stay in place for 30 minutes, during which they will be manually stimulated by rotation every 10 minutes to elicit the needle sensation. In the itopride plus sham acupuncture group and sham acupuncture plus placebo group, the patient’s position and disinfection methods will be the same as those in the acupuncture plus placebo group. Participants will receive a shallow puncture at non-acupoints. The selection of sham acupoints was based on published literature related to acupuncture for FD [11, 21 ], and these points are illustrated in Figure 2 and detailed in Table 1. Needles will be inserted perpendicularly to a depth of 0.3~0.5 cm at sham acupoints without any manipulation to avoid the de-qi sensation. The treatment frequency of verum acupuncture or sham acupuncture will be 3 times a week for 4 consecutive weeks, a total of 12 sessions. Itopride or placebo Patients assigned to the itopride plus sham acupuncture group will take 50 mg of itopride orally 3 times a day, 5 days per week, for 4 weeks. Participants in the acupuncture plus placebo group and sham acupuncture plus placebo group will receive an itopride placebo that is identical in taste and appearance to actual itopride tablet; they will follow the same frequency and dosage as the itopride plus sham acupuncture group. All patients are instructed to maintain a medication diary to document their usage and return unused medication. Outcome Primary outcomes in this study include the proportion of responders (PR) and the elimination rate of the main symptom. The secondary outcomes include changes in symptom score, QOL, and mood during the treatment and follow-up, as well as the participants’ expectancy for acupuncture before treatment. Table 2 display a summary of all measurements. Participants will keep an FD diary to record symptom severity, frequency, QOL, drug usage, and adverse events. Participants will complete the self-reported questionnaires based on the diary. Participants can seek assistance from research staff for any difficulties. The research staff should provide an unbiased explanation when responding to patient inquiries and should avoid influencing their judgment. Follow-up for all participants can be completed via social media (WeChat) or phone. Primary outcome The proportion of responders (PR): Positive responders are patients who had adequate relief of stomach discomfort (22). After receiving the weekly treatment, participants will be asked to measure changes in their symptom relief over the past 7 days using a 7-point Likert scale. This scale includes options of “extremely aggravated,” “aggravated,” “slightly aggravated,” “not changed,” “slightly improved,” “improved,” or “extremely improved,” corresponding to 0 to 6 points. Participants reporting a relief score of 5 or 6 points will be classified as positive responders. PR will be measured at week 2, week 3, week 4, week 5, week 9, week 13, and week 17. The elimination rate (ER): ER refers to the proportion of patients whose main symptoms have disappeared. According to Rome Ⅳ criteria, we define postprandial fullness and bloating as the main symptoms. Included patients should have at least one of these symptoms. Using a 7-point Likert scale, the main symptoms are considered to have disappeared if the rating drops to 0 after treatment. ER will be measured at week 2, week 3, week 4, week 5, week 9, week 13, and week 17. Secondary outcome The Chinese version of the Nepean Dyspepsia Symptom Index ( NDSI ) The NDSI is a validated, dyspepsia-specific questionnaire used to quantify the severity of 15 upper gastrointestinal symptoms in patients with FD over the prior 14 days [ 22 ]. Each symptom is evaluated on three dimensions, including frequency, scored on a 5-point Likert scale from absence (0 points) to continuous symptoms (4 points); intensity, scored on a 6-point Likert scale from absence (0 points) to very severe symptoms (5 points); and level of interference with activities of daily living, scored on a 5-point Likert scale from no interference (0 points) to severe interference (4 points). A higher total score on the NDSI indicates more severe dyspeptic symptoms. During the study, the NDSI scores will be measured at week 1, week 5, week 9, week 13, and week 17. The Chinese version of Short Form-Nepean Dyspepsia Life Quality Index (SF-NDLQI) TheSF-NDLQI instrument is an FD-specific 10-item questionnaire used to evaluate the impact of upper gastrointestinal symptoms on QOL across 5 domains: tension, interference with daily activities, eating/drinking, knowledge/control, and work/study [ 23 ]. Each domain has two items, and each item is scored from 1 to 5, with lower scores indicating higher quality of life. In this study, the SF-NDLQI will be administered at week 1, week 5, week 9, week 13, and week 17. The Chinese version of the Hospital Anxiety and Depression Scale (HADS) The HADS, a 14-item self-report questionnaire, will be utilized to assess the anxiety and depressive symptoms of patients. The HADS contains 7 items for anxiety (HADS-A) and 7 for depression (HADS-D), each scored from 0 to 3 with a total subscale score range of 0 to 21 [ 24 ]. Based on recommended cutoffs, anxiety and depression severity will be categorized as normal (0-7), mild (8-10), moderate (11-14), or severe (15-21) [ 25 ]. The HADS has demonstrated good reliability and validity in screening for anxiety and depression in general medical patients [ 26 ]. HADS will be measured at week 1, week 5, week 9, week 13, and week 17. Acupuncture expectation The Expectation for Treatment Scale (ETS), developed by Jürgen Barth and his colleagues, will be utilized to evaluate patients’ acupuncture expectations before treatment [ 27 ]. This scale comprises 5 items, such as “I anticipate that the treatment (acupuncture) will alleviate my complaints.” Each item is rated on a scale from 1 to 4, representing partial disagreement, partial agreement, agreement, and definite agreement, respectively. The total score ranges from 5 to 20. A higher total scale score indicates a greater expectation of achieving positive clinical outcomes. The ETS will be measured at week 1. Safety AEs are pivotal in evaluating the safety of treatments. All AEs, whether linked to the study treatment (acupuncture or itopride), will be recorded in the case report form (CRF). Each AE will be comprehensively described, including start/stop dates and times, severity, relationship to treatment, actions taken, and the necessity for treatment discontinuation. Researchers will closely monitor all AEs until they are resolved. In the case of serious AEs (e.g., events leading to disability, impaired ability to work, or life-threatening situations), immediate reporting will be made to both the research center and ethics committee. If any severe AEs associated with acupuncture arise, the ethics committee has the authority to consider suspending the trial. Data collection and management Clinical observers will complete a CRF for each participant to record all relevant clinical information. A dedicated data manager will then convert the paper-based CRF data to electronic format, with a secondary check by another research assistant to ensure data accuracy. Participants’ personal information will be anonymized and replaced with code for confidentiality during data collection. All data will be kept confidential, with electronic data secured on a password-protected server and paper data stored in locked cabinets. Access to clinical data will be restricted to authorized researchers only. Raw data will be retained for 5 years. The clinical inspectors/monitors will supervise the data collection and control for data completeness and quality. Quality control Before the study begins, the research center will provide standardized training sessions for the entire research team to ensure they follow the study protocol and become familiar with the administration process. Moreover, researchers will receive printed brochures detailing the trial procedures. Clinical researchers are encouraged to contact the research center for assistance if any technical or other issues arise at the clinical site. The research center should promptly provide practical guidance to address these issues. Registered acupuncturists with a minimum of five years of experience will perform the acupuncture treatment. These acupuncturists will undergo training and testing before the trial to ensure consistency in their acupuncture operation. A two-level quality inspection system will be established to ensure the implementation and quality of program. Inspectors at each center will conduct monthly quality examinations, while an independent monitoring team will carry out quality monitoring every three months. After each quality inspection, quality control reports should be submitted to the research center. Furthermore, any modifications to the research protocol must receive approval from the ethics committee. Sample size calculation The sample size for this study was determined based on the responder proportion at the end of a 4-week treatment, with 70.69% for the acupuncture treatment and 55.46% for the itopride treatment, as reported in a previous study [21]. The sample size calculation was performed using PASS 15.0 software, with a 1:1 ratio between the acupuncture plus placebo group and itopride plus sham acupuncture group. A statistical power of 80% (β=0.2), a one-sided alpha of 0.025 (α=0.025), and a non-inferiority margin of -10% (Δ=-10%) were considered in the calculation. The resulting sample size was 57 for each group. Accounting for a 15% dropout rate, each group needed 67 cases, resulting in a total enrollment of 201 cases across three groups. Statistical analysis Efficacy analyses will be performed on all random patients based on intention-to-treat principle. Missing data on the primary outcome will be imputed using the multiple imputation method under the missing at-random assumption. If there are significant differences in baseline variables between the two groups, those unbalanced variables will be included as covariates in the analysis of the primary outcome. We will establish confidence intervals at a 95% level, with a significance level set at 0.05. Continuous data will be reported as mean ± standard deviation (SD) if it is normally distributed. Otherwise, it will be reported as median (interquartile range). For longitudinal continuous data, we will compare groups using repeated-measures analysis of variance (ANOVA), taking into account both group and time-group interactions. Student’s t-test or Wilcoxon rank-sum test will be used for other continuous data. For categorical data, Χ 2 test or Fisher’s exact test will be applied as appropriate. The strength of linear relationships between variables will be evaluated using linear correlation analysis, and sensitivity analysis will be performed if required. The occurrence of AEs between groups will be summarized using descriptive analysis. Dissemination Policy We intend to publish the final trial results in medical journals related to functional gastrointestinal disorder or complementary and alternative medicine (CAM) within 2 years of completing the final data collection. Discussion There has been a growing focus in academia on effective treatment for FD in recent years. While some advancements have been achieved in drug treatment for FD [8], the effectiveness is not satisfactory and may come with side effects [9,10]. These problems compel patients to explore other safer and more effective methods in CAM. Acupuncture, a non-pharmacologic therapy in TCM, has been observed to be effective in reliving upper abdominal discomfort and improving QOL in FD patients [13,14]. However, there remains a lack of high-quality clinical studies and evidence supporting the use of acupuncture for FD treatment[8]. This study aims to assess the efficacy and safety of acupuncture for FD in a well-controlled trial design, providing evidence to support the clinical application of acupuncture. For better clinical management, the Rome Ⅲ Consensus proposed a symptom subtype classification of FD, and Rome Ⅳ Consensus adhered to this method [ 28 ]. Although it remains controversial whether there is any difference in pathogenesis between PDS and EPS [ 29 ], choosing a treatment plan based on FD subtypes has become a new trend [ 30 ]. Evidence shows that PDS is the most prominent subtype, affecting more than 60% of all FD patients [3,4]. Therefore, we selected PDS patients as the subjects of this study and diagnosed FD-PDS patients based on Rome Ⅳ criteria. Though multiple mechanisms contribute to PDS development, gastric sensorimotor function disorder has been considered a vital factors [30]. Prokinetic agents have been recommended as the first-choice treatment for PDS patients in a Chinese consensus [ 31 ]. Itopride is a prokinetic agent with a response rate of 55%-73% in treating FD and minimal side effects [11, 32 , 33 ]. Therefore, we used itopride as a positive drug to evaluate the efficacy of acupuncture in treating PDS, thereby providing more clinical treatment decision-making references. Five acupoints are selected in this protocol based on findings from clinical and basic research: Sibai (ST2), Zusanli (ST36), Liangmen (ST21), Neiguan (PC6), and Gongsun (SP4). A previous clinical study has shown that acupuncture at above five acupoints can further alleviate discomfort in upper abdominal and improve patients’ QOL based on mosapride treatment [ 34 ]. ST2, ST36, and ST21 belong to the Yangming stomach meridian of the foot, commonly applied in digestive-system diseases. These three acupoints can regulate the disturbed qi and blood and normalize spleen and stomach function. In particular, acupuncture at ST36 has been proven to improve the gastric function of FD model rats by reducing low-grade inflammation of duodenal mucosal, accelerating gastric emptying, and reducing gut visceral hypersensitivity [ 35 , 36 ]. PC6 and SP4 are both Ba-mai Jiao-hui points. The traditional meridian theory believes that stimulating PC6 and SP4 can positively affect the gastrointestinal tract function and emotional state. Our previous basic studies indicated that acupuncture at PC6 and SP4 could improve gastrointestinal motility disorders, visceral hypersensitivity, and the anxiety and depression-like behavior in rats with FD [ 37 , 38 ]. Therefore, we selected ST2, ST36, ST21, PC6, and SP4 as our acupuncture acupoints. To our knowledge, this is the first multicentre, randomized, double-dummy, single-blind, active-controlled trial on the efficacy and safety of acupuncture for treating PDS. The physical nature of acupuncture treatment poses challenges to the design of sham acupuncture. Nonetheless, researchers use a variety of methods to achieve the placebo effect of acupuncture, including regular needling on non-points, shallow needling on points or non-points, and nonpenetrating needling based on various devices [ 39 ]. It is reported that different sham acupuncture treatments can produce different placebo effects of varying sizes [ 40 ]. A previous study related to pain relief from acupuncture found that the placebo effect of shallow puncture at non-points is much smaller than shallow puncture at point, deep puncture at nonacupoints, and nonpenetration acupuncture [ 41 ]. Ma et al. and Jing et al. reported a significant difference in improving symptoms and QOL among FD patients between regular acupuncture and shallow puncture at non-points [11,21]. Therefore, sham acupuncture was administrated by a shallow puncture at non-points in this trial. Besides proper blinding, we also apply strict quality control measures, blind outcome assessment, concealed treatment allocation, and intention-to-treat analysis to minimize bias and increase the credibility of the results. However, several limitations of this trial should be noted. Although participants and assessors were blinded in this trial, treatment personnel can not be further blinded due to the inherent nature of acupuncture. Therefore, it cannot be ruled out that performance bias influences the results. Second, this trial only includes patients from Changsha City; whether the results can be applied to other populations or regions requires further research. Finally, we designed a standardized acupuncture regimen without considering individual differences among patients, which may limit the efficacy of acupuncture. To summarize, the outcome of this study aims to validate the effectiveness and safety disparity between acupuncture and Itopride in treating PDS. These results will serve as a dependable foundation to endorse the practical use of acupuncture in managing FD. Trial status This clinical trial has yet to start. Recruitment is scheduled to begin in September 2024 and be completed by December 2026. Abbreviations FD = Functional dyspepsia; EPS = epigastric pain syndrome; PDS = postpandial distress syndrome; TCM = Traditional Chinese Medicine; SPIRIT = Standard Protocol Items: Recommendations for Interventional Trials; STRICTA = Standards for Reporting Interventions in Controlled Trials of Acupuncture; QOL = quality of life; PR = proportion of responders; AR = adequate relief; NDSI = Nepean Dyspepsia Symptom Index; SF-NDLQI = The Short Form-Nepean Despepsia Life Quality Index; HADS = Hospital Anxiety and Depression Scale; ETS = The Expectation for Treatment Scale; AEs = Adverse events; CRF = case reported form; SD = standard deviation; ANOVA = one-way analysis of variance; CAM = complementary and alternative medicine. Declarations Acknowledgments We would like to thank the patients and researchers who participated in the study. Author contributions Mi Liu is the principal investigator of this trial and is fully responsible for the design and implementation. Mi Liu and Geshu Du collaborated on designing a preliminary study protocol, which included the study’s purpose, grouping, and outcomes. Zhimiao Murong and Mailan Liu calculated the sample size and selected suitable statistical methods. Zhaobo Yan and Xuan Xu were responsible for writing the first draft of the manuscript. Huan Zhong and Haolong He were in charge of revising the protocol manuscript. Rong Luo, Weiai Liu, and Geshu Du provided technical and methodological support. All authors read and approved the final manuscript. Funding This research was funded by the Hunan Province TCM Science and Technology Plan Project (No.C2022027, No.D2022005), the National Natural Science Foundation of China (No. 81904097, No. 82374598), the Hunan Provincial Department of Education Funding for Scientific Research Project (No.21A0235, No.23A0284), the National Administration of Traditional Chinese Medicine 2022 Young Qihang Scholar Training Project (State Administration of Traditional Chinese Medicine Letter [2022] No. 256), the Hunan Province Natural Science Project (No.2023JJ30457), the Key Research Project of Health High-level Talents of Hunan Province (No.R2023141), the General Project of Hunan Provincial Health Commission (No.W20243084), the Changsha Natural Science Foundation Project (No.kq2208183), and the Postgraduate Research Innovation Program of Hunan Province (No. QL20220188). Availability of data and materials Details of this study are available from the corresponding author upon request. Ethics approval and consent to participate The research methodology followed the ethical standards stated in the Declaration of Helsinki. It also adhered to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines and the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) checklist. The study protocol obtained approval from the Medical Ethics Committee of the Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine (No. 2023-KY-22). Furthermore, it was registered with the Chinese Clinical Trial Registry (ChiCTR2300068001). All patients were well informed and signed an informed consent form before enrollment. Consent for publication Not applicable. Conflict of interest The authors declare no conflict of interest. References Oshima T. Functional Dyspepsia: Current Understanding and Future Perspective. Digestion.2024;105(1):26-33. Lee K, Kwon CI, Yeniova AÖ, Koyanagi A, Jacob L, Lee SW, et al. 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Ma YY, Hao Z, Chen ZY, Shen YX, Liu HR, Wu HG, et al. Acupuncture and moxibustion for irritable bowel syndrome:An umbrella systematic review. J Integr Med. 2024;22(1):22-31. Ho RST, Chung VCH, Wong CHL, Wu JCY, Wong SYS, Wu IXY. Acupuncture and related therapies used as add-on or alternative to prokinetics for functional dyspepsia: overviewof systematic reviews and network meta-analysis. Sci Rep. 2017;7(1):10320. Zhang J, Liu Y, Huang X, Chen Y, Hu L, Lan K, et al. Efficacy Comparison of Different Acupuncture Treatments for Functional Dyspepsia: A Systematic Review with Network Meta-Analysis. Evid Based Complement Alternat Med. 2020;2020:3872919. Kwon CY, Ko SJ, Lee B, Cha JM, Yoon JY, Park JW. Acupuncture as an Add-On Treatment for Functional Dyspepsia: A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2021;8:682783. Liu YL, Li SS, Yang YR, Zhao YH, Li WX, Hao JX, et al. Research progress on the molecular mechanism of electroacupuncture at \"Zusanli\" (ST36) for regulating gastrointestinaldysfunction [in Chinese]. Zhen Ci Yan Jiu. 2023;48(10):1048-54. Li DD, Yue ZH, Xu LC, Xie T, Hu GZ, Yang J. Clinical evaluation study on long-term effect of acupuncture with pattern/syndrome differentiation on functional dyspepsia [in Chinese]. Chin Acupunct & Mox. 2014;34(5):431-434. Xu Fan. The Clinical Study on the Treatment of Functional Dyspepsia of Disharmony of liver and Stomach with Acupuncture Therapy by dispersing the Stagnated liver-Qi and Regulating the Spirit [master’s thesis]. Chengdu, China: Chengdu University Of Chinese Medicine; 2021. Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, A-Jerić KK, et al. SPIRIT 2013 Statement: defining standard protocol items for clinical trials. Rev Panam SaludPublica. 2015;38(6):506-14. MacPherson H, Altman DG, Hammerschlag R, Youping L, Taixiang W, White A, et al. Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): extending the CONSORT statement. J Altern Complement Med. 2010;16(10):ST1-14. Yang JW, Wang LQ, Zou X, Yan SY, Wang Y, Zhao JJ, et al. Effect of Acupuncture for Postprandial Distress Syndrome: A Randomized Clinical Trial. Ann Intern Med. 2020;172(12):777-85. Tian XP, Li Y, Liang FR, Sun GJ, Yan J, Chang X R, et al. Translation and validation ofthe Nepean Dyspepsia Index for functional dyspepsia in China. World J Gastroenterol. 2009;15(25):3173-77. Talley NJ, Verlinden M, Jones M. Quality of life in functional dyspepsia: responsiveness of the Nepean Dyspepsia Index and development of a new 10-item short form. Aliment Pharmacol Ther. 2001;15(2):207-16. Lloyd M, Sugden N, Thomas M, McGrath A, Skilbeck C. The structure of the Hospital Anxiety and Depression Scale: Theoretical and methodological considerations. Br J Psychol. 2023;114(2):457-75. Hatch R, Young D, Barber V, Griffiths J, Harrison DA, Watkinson P. Anxiety, Depression and Post Traumatic Stress Disorder after critical illness: a UK-wide prospective cohort study. Crit Care. 2018;22(1):310. Beekman E,Verhagen A. Clinimetrics: Hospital Anxiety and Depression Scale. J Physiother. 2018;64(3):198. Barth J, Kern A, Lüthi S, Witt CM. Assessment of patients' expectations: developmentand validation of the Expectation for Treatment Scale (ETS). BMJ Open. 2019;9(6):e026712. Van den Houte K, Carbone F, Goelen N, Schol J, Masuy I, Arts J, et al. Effects of Rome IV Definitions of Functional Dyspepsia Subgroups in Secondary Care. Clin Gastroenterol Hepatol. 2021;19(8):1620-26. Fang YJ, Liou JM, Chen CC, Lee JY, Hsu YC, Chen MJ, et al. Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria. Gut. 2015;64(10):1517-28. Van Den Houte K,Carbone F,Tack J. Postprandial distress syndrome: stratification and management. Expert Rev Gastroenterol Hepatol. 2019;13(1):37-46. Gastrointestinal Dynamics Group, Chinese Society of Gastroenterology, Chinese Medical Association, Functional Gastrointestinal Disease Collaborative Group, Chinese Society of Gastroenterology, Chinese Medical Association. 2022 expert consensus on diagnosis and treatment of functional dyspepsia in China. Chinese Journal of Digestion, 2019;43(07):433-66. Holtmann G, Talley NJ, Liebregts T, Adam B, Parow C. A placebo-controlled trial of itopride in functional dyspepsia. N Engl J Med. 2006;354(8):832-40. Talley NJ, Tack J, Ptak T, Gupta R, Giguère M. Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials. Gut. 2008;57(6):740-46. Ye Y, Zhu LB, Tan YG. Therapeutic Observation of Three-segment Point Selection plus Mosapride for Functional Dyspepsia [in Chinese]. Shanghai J Acu-mox. 2018;37(10):1136-39. Dong JZ, Rong PJ, Wang XT, Wang D, Leng MH, Xiao LJ. Effect of electroacupuncture at \"Zusanli\" (ST 36) on duodenal mast cells, NGF and NTRK1 in rats with functional dyspepsia [in Chinese]. Zhongguo Zhen Jiu. 2022;42(7):767-72. Dong JZ, Rong PJ, Ma TM, Wang D, Wang XT, Qiao Y. Influence of electroacupuncture of\"Zusanli\"(ST36)on mast cells/TRPV1 signaling pathway in visceral hypersensitivity rats with functional dyspepsia [in Chinese]. Zhen Ci Yan Jiu. 2022;47(7):592-7. Wu PX, Jiang Y, Qin SM, Xing BW, Shi HB, Xie YF, et al. Effects of electroacupuncture on the hypothalamic CRF and its receptors CRF1 and CRF2 in FD rats at theeight confluenence points Neiguan (PC6) and Gongsun (SP4) [in Chinese]. CJTCMP.2023;38(7):3343-46. Xie YF, Tan SM, Zhan LF, Xing BW, Liu WA. Effects of electroacupuncture at Neiguan and Gongsun acupoints on spleen index and thymus index of FD model rats [in Chinese]. Clin J Chin Med. 2023;15(15):104-7. Birch S, Lee MS, Kim TH, Alraek T. Historical perspectives on using sham acupuncture in acupuncture clinical trials. Integr Med Res. 2022;11(1):100725. Xiong ZY, Liu XY, Ma PH, Sun CY, Sun CY, Liu TL, et al. Placebo Response among Different Types of Sham Acupuncture for Low Back Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Chin J Integr Med. 2023;29(10):941-50. Zeng D, Yan XX, Deng HM, Li JM, Xiao JX, Yuan JW, et al. Placebo response varies between different types of sham acupuncture: A randomized double-blind trial in neck pain patients. Eur J Pain. 2022;26(5):1006-20. Tables Table 1 Locations and manipulations of acupoints Acupoint Location Depth of needle penetration Manipulation Sibai (ST2) RA1 In the face, directly below the pupil, and in the depression of the infraorbital foramen. Inserted perpendicularly at 0.5 cun with 0.20mm*13mm acupuncture needles. Elicit de-qi sensation by manual stimulation. NA1 In the face, 1 cun horizontally next to Sibai. Inserted perpendicularly at 0.3 cm with 0.20mm*13mm acupuncture needles. Without manipulation, avoid de-qi sensation. Liangmen (ST21) RA2 In the abdomen, 4 cun above the umbilicus, and 2 cun lateral to the anterior midline. Inserted perpendicularly at 0.8-1.2 cun with 0.3mm*40mm acupuncture needles. Elicit de-qi sensation by manual stimulation. NA2 In the abdomen, 2 cun horizontally next to Liangmen. Inserted perpendicularly at 0.5 cm with 0.3mm*40mm acupuncture needles. Without manipulation, avoid de-qi sensation. Neiguan (PC6) RA3 In the flexor aspect of the forearm, between the tendons of palmaris longus and flexor carpi radialis, 2 cun above the transverse crease of the wrist. Inserted perpendicularly at 0.5-1 cun with 0.30mm*25mm acupuncture needles. Elicit de-qi sensation by manual stimulation. NA3 In the midpoint of the line connecting Lingdao (HT4) and Xiaohai (SI8) on the inner side of the forearm. Inserted perpendicularly at 0.3 cm with 0.30mm*25mm acupuncture needles. Without manipulation, avoid de-qi sensation. Zusanli (ST36) RA4 In the anterior aspect of the lower leg, 3 cun directly below Dubi (ST35), and one finger-breadth lateral to the anterior border of the tibia. Inserted perpendicularly at 1-2 cun with 0.3mm*40mm acupuncture needles Elicit de-qi sensation by manual stimulation. NA4 In the anterior aspect of the lower leg, the midpoint of the line connecting Zusanli (ST36) and Yangjiao (GB35). Inserted perpendicularly at 0.5 cm with 0.3mm*40mm acupuncture needles Without manipulation, avoid de-qi sensation. Gongsun (SP4) RA5 In the anterior and inferior of the base of the first metatarsal bone, and on the dorso-ventral boundary. Inserted perpendicularly at 0.5-1 cun with 0.30mm*25mm acupuncture needles Elicit de-qi sensation by manual stimulation. NA5 In the dorsum of the foot, the midpoint of the line connecting Gongsun (SP4) and Zhongfeng (LR4). Inserted perpendicularly at 0.3 cm with 0.30mm*25mm acupuncture needles. Without manipulation, avoid de-qi sensation. 1 cun is defined as the width of the interphalangeal joint of the patient's thumb. Dubi (ST35) is in the lateral depression of the patellar ligament when the knee is flexed. Lingdao (HT4) is located on the anteromedial aspect of the wrist, radial to the flexor carpi ulnaris tendon, 1.5 cun above the transverse striation of the wrist. Xiaohai (SI8) is located in the depression between the ulna's olecranon and the humerus's medial epicondyle. Yangjiao (GB35) is located at the lateral legs, 7 cun above the lateral malleolus tip, at the posterior margin of the fibula. Zhongfeng (LR4) is located at the anterior medial malleolus, in the depression on the medial edge of the tibialis anterior tendon. RA: real acupoints; NA: non-acupoints. Table 2 SPIRIT figure for the schedule of enrollment, interventions, and assessments. STUDY PERIOD Enrolment Allocation Treatment phase Follow-up TIMEPOINT** 1w 2w 3w 4w 5w 9w 13w 17w ENROLMENT: Eligibility screen X Informed consent X Allocation X INTERVENTIONS: Acupuncture group Drug group ASSESSMENTS: Proportion of responders X X X X X X X Elimination rate X X X X X X X NDSI X X X X X SF-NDLQI X X X X X HADS X X X X X Acupuncture expectation X Adverse events X X X X SPIRIT = standard protocol items: recommendations for interventional trials; NDSI = the nepean dyspepsia symptom index; FD-QOL = functional dyspepsia-related quality of life; HADS = Hospital Anxiety and Depression Scale. Additional Declarations No competing interests reported. Supplementary Files additionalfile1TheSPIRIT2013Checklist.docx additionalfile2TheSTRICTAChecklist.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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A recent meta-analysis suggests it impacts 8.4% of adults worldwide [\\u003csup\\u003e2\\u003c/sup\\u003e]. The Rome IV criteria categorizes FD into three subtypes: epigastric pain syndrome (EPS), postprandial distress syndrome (PDS), and the overlapping form of EPS/PDS [1]. PDS, the most common subtype, presents with meal-related symptoms such as postprandial fullness and early satiety. Epidemiological studies from various countries show that PDS accounts for about 60% of FD cases [\\u003csup\\u003e3\\u003c/sup\\u003e,\\u003csup\\u003e4\\u003c/sup\\u003e] and is more prevalent in Asian populations compared to Western populations[\\u003csup\\u003e5\\u003c/sup\\u003e]. Although not life-threatening, the chronic and recurrent nature of FD symptoms significantly impacts patients\\u0026rsquo; psychological well-being, quality of life (QOL), and social functioning [\\u003csup\\u003e6\\u003c/sup\\u003e]. Furthermore, FD imposes a considerable economic burden, with an average yearly direct cost of $699 per patient in the United States [\\u003csup\\u003e7\\u003c/sup\\u003e]. Therefore, FD has become a significant public health concern requiring heightened clinical attention and research endeavors.\\u003c/p\\u003e\\n\\u003cp\\u003eThe effective treatment of FD remains an unsolved clinical challenge. FD is recognized as a complex condition with several factors participating in its development, including gastric motility disorder, increased gastric acid secretion, psychosocial disorders, and Helicobacter pylori infection [1,6]. Although drugs such as prokinetic agents, acid suppressants, antidepressants, anti-Helicobacter pylori medications, and mucosal protectants have been officially recommended for the treatment of FD, single-drug therapy may not address all of the underlying pathophysiological mechanisms of FD, leading to limited efficacy [\\u003csup\\u003e8\\u003c/sup\\u003e]. Additionally, these medications may be limited by side effects [\\u003csup\\u003e9\\u003c/sup\\u003e,\\u003csup\\u003e10\\u003c/sup\\u003e]. Therefore, physicians and patients expect more treatments for FD that are both effective and low-risk.\\u003c/p\\u003e\\n\\u003cp\\u003eAcupuncture is an important part of traditional Chinese medicine (TCM), boasting a history of thousands of years. Acupuncture has rich experience in preventing and treating digestive system diseases; it can be utilized for improving various digestive symptoms, including stomach pain, bloating, nausea, vomiting, diarrhea, and constipation [\\u003csup\\u003e11\\u003c/sup\\u003e,\\u003csup\\u003e12\\u003c/sup\\u003e]. Currently, the acceptance of acupuncture is increasing gradually worldwide. Multiple meta-analyses revealed that acupuncture is more effective than the single use of prokinetic drugs or sham acupuncture in improving digestive symptoms and quality of life in patients with FD [\\u003csup\\u003e13\\u003c/sup\\u003e,\\u003csup\\u003e14\\u003c/sup\\u003e]. Moreover, another system review found that acupuncture combined with Western medicine has a synergistic effect in the treatment of FD while helping to reduce the relapse rate within 3~6 months after treatment [\\u003csup\\u003e15\\u003c/sup\\u003e]. Additionally, the evidence has shown that acupuncture can regulate gastrointestinal function by improving gastrointestinal motility and reducing visceral sensitivity, which supports the potential of acupuncture as a therapeutic option for FD [\\u003csup\\u003e16\\u003c/sup\\u003e]. However, due to limited high-quality evidence (evidence grade B), a recent consensus statement did not endorse acupuncture for FD, highlighting the need for further high-quality RCTs to clarify its therapeutic potential and role in FD management [8].\\u003c/p\\u003e\\n\\u003cp\\u003ePrevious clinical trials have compared the therapeutic effects of acupuncture with prokinetic agents in patients with FD, revealing acupuncture as a superior way to prokinetic agents [\\u003csup\\u003e17\\u003c/sup\\u003e,\\u003csup\\u003e18\\u003c/sup\\u003e]. However, these studies were open-lable and lacked blinding, potentially allowing patient preferences for acupuncture to influence clinical outcomes. To obtain more high-quality evidence, we design a new randomized trial; this trial will administer different treatments (acupuncture or the drug itopride) in a double-dummy, single-blind design to objectively evaluate the effectiveness and safety of acupuncture for PDS compared to itopride.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eStudy design\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis clinical study is a multicentre, single-blind, double-dummy, randomised, active-controlled trial that compares the efficacy and safety of acupuncture versus itopride in improving upper abdominal discomfort in patients with PDS. The study protocol has been registered with the Chinese Clinical Trial Registry (ChiCTR2300068001). It adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines (Additional file 1) [\\u003csup\\u003e19\\u003c/sup\\u003e] as well as the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) checklist (Additional file 2) [\\u003csup\\u003e20\\u003c/sup\\u003e]. The study flowchart is shown in Figure 1.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eStudy setting and recruitment\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis clinical trial will be conducted collaboratively by an academic center and three clinical institutions. Researchers from the Hunan University of Chinese Medicine will form an academic center group responsible for experimental design, data analysis and results dissemination. Recruitment, treatment and data collection will occur at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, the Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, and Changsha Hospital of Traditional Chinese Medicine. Recruitment is scheduled to take place at inpatient and outpatient departments in three medical centers, and start in September 2024, with the follow-up assessments of all participants completed by December 2026. Recruitment information will be disseminated through various means such as paper flyers, posters, and social platform like Wechat. Participants interested in this trial will be informed about the purpose and process of the study as well as potential risks and benefits. If the patient decides to participate after understanding this information, they will undergo a clinical screening evaluation conducted by registered TCM practitioners with a minimum of 5 years of clinical experience. Eligible patients will sign an informed consent form, receive baseline assessment, and be randomly assigned.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEligibility criteria\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eInclusion criteria\\u003c/em\\u003e\\u003c/strong\\u003e\\u003cstrong\\u003e：\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe study will involve individuals who meet the following criteria:\\u003c/p\\u003e\\n\\u003col style=\\\"list-style-type: lower-roman;\\\"\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eAged 18-60 years and long-term residents of Changsha.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eDiagnosed with FD-PDS according to the Rome IV criteria.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eNo structural abnormalities were detected through upper gastrointestinal endoscopy surveillance.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eNon-refractory FD.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003ePatients who are helicobacter pylori-negative or have persistent symptoms after helicobacter pylori eradication for one month.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eGood compliance.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003c/ol\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eExclusion criteria\\u003c/em\\u003e\\u003c/strong\\u003e\\u003cstrong\\u003e：\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe following individuals will be excluded from the study:\\u003c/p\\u003e\\n\\u003col style=\\\"list-style-type: lower-roman;\\\"\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eUse drugs, such as prokinetics, acid suppression, mucosal protectants, or other FD-related agents, within 2 weeks.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eDo not tolerate acupuncture.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eReceive acupuncture treatment within 2 weeks.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eHave gastrointestinal diseases other than PDS.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003ePregnant or lactating women and those attempting conception.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003ePatients who are participating in other clinical trials.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eDiagnosed with malignancy or other serious conditions, such as severe heart, liver, lung, or kidney dysfunction, severe autoimmune disease, or endocrine diseases.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eUnable to effectively communicate for any reason, such as severe mental illness, cognitive impairment, or impaired language comprehension.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003c/ol\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eDropout exclusion criteria\\u003c/em\\u003e\\u003c/strong\\u003e\\u003cstrong\\u003e\\u003cem\\u003e：\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePatients who discontinue treatment due to any of the following reasons (including but not limited to) will be a dropout case：\\u003c/p\\u003e\\n\\u003col style=\\\"list-style-type: lower-roman;\\\"\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eVoluntary withdrawal by participants for any personal reasons.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eThe patient\\u0026rsquo;s symptoms don\\u0026rsquo;t improve and gradually worsened after treatment.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003ePatients are unreachable due to relocated or changed contact information.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003ePatients undergo changes in health status that need a timely manner.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003ePatients experience intolerable side effects and are unwilling to continue treatment.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003c/ol\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eExit/termination criteria\\u003c/em\\u003e\\u003c/strong\\u003e\\u003cstrong\\u003e:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003col style=\\\"list-style-type: lower-roman;\\\"\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003ePatients do not meet the inclusion criteria and are enrolled mistakenly.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003ePatients receive other or additional FD treatments during the study period.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003c/ol\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eStrategies to improve adherence to interventions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eIn order to mitigate the impact of dropout rates on research quality, we will enhance participant compliance through several strategies:\\u003c/p\\u003e\\n\\u003col style=\\\"list-style-type: lower-roman;\\\"\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eResearchers will regularly contact with participants via WeChat or phone calls to understand their condition and remind them about the schedule of their next visit.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eWe will schedule treatment and evaluation sessions at convenient times to minimize disrupting participants' work and daily lives.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eThe evaluation process will be simplified to enhance patient engagement.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eParticipants will be reimbursed for treatment expenses and transportation costs to and from the hospital.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003e\\n\\u003cp\\u003eDedicated staff will be available to address any study-related inquiries raised by participants.\\u003c/p\\u003e\\n\\u003c/li\\u003e\\n\\u003c/ol\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eRandomization, allocation, and concealment\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eA research assistant at each clinical center will conduct random assignments independently from other study activities. Eligible patients will be randomly assigned into the acupuncture plus placebo group, itopride plus sham acupuncture group, and sham acupuncture plus placebo group in a 1:1:1 ratio. A professional statistician will utilize SAS software (v9.3) to produce a list of random numbers stratified by clinical institution using block sizes of 6 or 9. The randomization process will be carried out through an online central randomization system. The randomization number and group assignment provided to each patient by the randomization system will be unique and unchangeable, ensuring fairness in treatment allocation.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eBlinding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis study will maintain blinding among patients, observers, and statisticians. However, acupuncturists will not be blinded due to the nature of the acupuncture procedure. Patients will be informed that the study involves two types of acupuncture treatment and two types of drug, which theoretically can improve PDS symptoms. Regardless of their assigned group, patients will receive a combination treatment comprising one type of acupuncture treatment and one type of drug. Sham acupuncture will be performed by superficial needling on non-acupoints to mimic the verum acupuncture treatment successfully. Itopride placebo tablets will be indistinguishable from verum itopride tablets in taste and appearance. Each patient will undergo treatment in separate rooms to prevent communication between them. Acupuncturists, who will not be blinded, must refrain from discussing assignment information with participants. In the case the trial goes well, the research center will perform unblinding once the statistical analysis is complete. However, if any emergencies arise, such as life-threatening adverse events (AEs), the acupuncturists will perform urgent unblinding. The monitoring team and ethics committee will then analyze the relationship between patient intervention strategies and AEs.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eIntervention\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis trial consists of a screening phase (1 week), a treatment phase (4 weeks), and a post-treatment follow-up phase (12 weeks). During the treatment period, participants in the acupuncture plus placebo group will receive 12 sessions of verum acupuncture treatment and itopride placebo tablets for 20 days. Patients in the itopride plus sham acupuncture group will take itopride tablets for 20 days and receive 12 sessions of sham acupuncture treatment. Patients in the placebo plus sham acupuncture group will take itopride placebo tablets for 20 days and receive 12 sessions of sham acupuncture treatment. The detailed treatment procedures is as follows:\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eVerum or sham acupuncture\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eParticipants in the acupuncture plus itopride group will receive verum acupuncture at 5 specific acupoints: SiBai (ST2), Liangmen (ST21), Zusanli (ST36), Neiguan (PC6), and Gongsun (SP4). This acupoint protocol is based on our prior clinical research on acupuncture for FD. The location of all acupoints is illustrated in Figure 2 and detailed in Table 1, following the Nomenclature and location of acupuncture points per the Chinese National Standard (GB/T22163-2008). Patients will be supine and maintain mental relaxation as per practitioner instruction. Acupuncturists will sterilize both the needle (Huatuo brand, Suzhou Medical Supplies Factory, China) and the skin at the acupoint locations before insertion. The depth of needle penetration will vary depending on the acupoints, refer to Table 1 for details. After the needles penetrate the skin, acupuncturists will manipulated them with lifting, inserting, or twisting movements until patients feel the Deqi sensation. The needles will be stay in place for 30 minutes, during which they will be manually stimulated by rotation every 10 minutes to elicit the needle sensation.\\u003c/p\\u003e\\n\\u003cp\\u003eIn the itopride plus sham acupuncture group and sham acupuncture plus placebo group, the patient\\u0026rsquo;s position and disinfection methods will be the same as those in the acupuncture plus placebo group. Participants will receive a shallow puncture at non-acupoints. The selection of sham acupoints was based on published literature related to acupuncture for FD [11,\\u003csup\\u003e21\\u003c/sup\\u003e], and these points are illustrated in Figure 2 and detailed in Table 1. Needles will be inserted perpendicularly to a depth of 0.3~0.5 cm at sham acupoints without any manipulation to avoid the de-qi sensation.\\u003c/p\\u003e\\n\\u003cp\\u003eThe treatment frequency of verum acupuncture or sham acupuncture will be 3 times a week for 4 consecutive weeks, a total of 12 sessions.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eItopride or placebo\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePatients assigned to the itopride plus sham acupuncture group will take 50 mg of itopride orally 3 times a day, 5 days per week, for 4 weeks. Participants in the acupuncture plus placebo group and sham acupuncture plus placebo group will receive an itopride placebo that is identical in taste and appearance to actual itopride tablet; they will follow the same frequency and dosage as the itopride plus sham acupuncture group. All patients are instructed to maintain a medication diary to document their usage and return unused medication.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eOutcome \\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePrimary outcomes in this study include the proportion of responders (PR) and the elimination rate of the main symptom. The secondary outcomes include changes in symptom score, QOL, and mood during the treatment and follow-up, as well as the participants\\u0026rsquo; expectancy for acupuncture before treatment. Table 2 display a summary of all measurements. Participants will keep an FD diary to record symptom severity, frequency, QOL, drug usage, and adverse events. Participants will complete the self-reported questionnaires based on the diary. Participants can seek assistance from research staff for any difficulties. The research staff should provide an unbiased explanation when responding to patient inquiries and should avoid influencing their judgment. Follow-up for all participants can be completed via social media (WeChat) or phone.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003ePrimary outcome\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eThe \\u003c/strong\\u003e\\u003cstrong\\u003eproportion of responders (PR):\\u003c/strong\\u003e Positive responders are patients who had adequate relief of stomach discomfort (22). After receiving the weekly treatment, participants will be asked to measure changes in their symptom relief over the past 7 days using a 7-point Likert scale. This scale includes options of \\u0026ldquo;extremely aggravated,\\u0026rdquo; \\u0026ldquo;aggravated,\\u0026rdquo; \\u0026ldquo;slightly aggravated,\\u0026rdquo; \\u0026ldquo;not changed,\\u0026rdquo; \\u0026ldquo;slightly improved,\\u0026rdquo; \\u0026ldquo;improved,\\u0026rdquo; or \\u0026ldquo;extremely improved,\\u0026rdquo; corresponding to 0 to 6 points. Participants reporting a relief score of 5 or 6 points will be classified as positive responders. PR will be measured at week 2, week 3, week 4, week 5, week 9, week 13, and week 17.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eThe elimination rate (ER): \\u003c/strong\\u003eER refers to the proportion of patients whose main symptoms have disappeared. According to Rome Ⅳ criteria, we define postprandial fullness and bloating as the main symptoms. Included patients should have at least one of these symptoms. Using a 7-point Likert scale, the main symptoms are considered to have disappeared if the rating drops to 0 after treatment. ER will be measured at week 2, week 3, week 4, week 5, week 9, week 13, and week 17.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eSecondary outcome\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eThe Chinese version of the Nepean Dyspepsia Symptom Index (\\u003c/strong\\u003e\\u003cstrong\\u003eNDSI\\u003c/strong\\u003e\\u003cstrong\\u003e) \\u003c/strong\\u003eThe NDSI is a validated, dyspepsia-specific questionnaire used to quantify the severity of 15 upper gastrointestinal symptoms in patients with FD over the prior 14 days [\\u003csup\\u003e22\\u003c/sup\\u003e]. Each symptom is evaluated on three dimensions, including frequency, scored on a 5-point Likert scale from absence (0 points) to continuous symptoms (4 points); intensity, scored on a 6-point Likert scale from absence (0 points) to very severe symptoms (5 points); and level of interference with activities of daily living, scored on a 5-point Likert scale from no interference (0 points) to severe interference (4 points). A higher total score on the NDSI indicates more severe dyspeptic symptoms. During the study, the NDSI scores will be measured at week 1, week 5, week 9, week 13, and week 17.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eThe Chinese version of Short Form-Nepean Dyspepsia Life Quality Index (SF-NDLQI) \\u003c/strong\\u003eTheSF-NDLQI instrument is an FD-specific 10-item questionnaire used to evaluate the impact of upper gastrointestinal symptoms on QOL across 5 domains: tension, interference with daily activities, eating/drinking, knowledge/control, and work/study [\\u003csup\\u003e23\\u003c/sup\\u003e]. Each domain has two items, and each item is scored from 1 to 5, with lower scores indicating higher quality of life. In this study, the SF-NDLQI will be administered at week 1, week 5, week 9, week 13, and week 17.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eThe Chinese version of the Hospital Anxiety and Depression Scale (HADS)\\u003c/strong\\u003e The HADS, a 14-item self-report questionnaire, will be utilized to assess the anxiety and depressive symptoms of patients. The HADS contains 7 items for anxiety (HADS-A) and 7 for depression (HADS-D), each scored from 0 to 3 with a total subscale score range of 0 to 21 [\\u003csup\\u003e24\\u003c/sup\\u003e]. Based on recommended cutoffs, anxiety and depression severity will be categorized as normal (0-7), mild (8-10), moderate (11-14), or severe (15-21) [\\u003csup\\u003e25\\u003c/sup\\u003e]. The HADS has demonstrated good reliability and validity in screening for anxiety and depression in general medical patients [\\u003csup\\u003e26\\u003c/sup\\u003e]. HADS will be measured at week 1, week 5, week 9, week 13, and week 17.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcupuncture expectation \\u003c/strong\\u003eThe Expectation for Treatment Scale (ETS), developed by J\\u0026uuml;rgen Barth and his colleagues, will be utilized to evaluate patients\\u0026rsquo; acupuncture expectations before treatment [\\u003csup\\u003e27\\u003c/sup\\u003e]. This scale comprises 5 items, such as \\u0026ldquo;I anticipate that the treatment (acupuncture) will alleviate my complaints.\\u0026rdquo; Each item is rated on a scale from 1 to 4, representing partial disagreement, partial agreement, agreement, and definite agreement, respectively. The total score ranges from 5 to 20. A higher total scale score indicates a greater expectation of achieving positive clinical outcomes. The ETS will be measured at week 1.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eSafety\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAEs are pivotal in evaluating the safety of treatments. All AEs, whether linked to the study treatment (acupuncture or itopride), will be recorded in the case report form (CRF). Each AE will be comprehensively described, including start/stop dates and times, severity, relationship to treatment, actions taken, and the necessity for treatment discontinuation. Researchers will closely monitor all AEs until they are resolved. In the case of serious AEs (e.g., events leading to disability, impaired ability to work, or life-threatening situations), immediate reporting will be made to both the research center and ethics committee. If any severe AEs associated with acupuncture arise, the ethics committee has the authority to consider suspending the trial.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData collection and management\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eClinical observers will complete a CRF for each participant to record all relevant clinical information. A dedicated data manager will then convert the paper-based CRF data to electronic format, with a secondary check by another research assistant to ensure data accuracy. Participants\\u0026rsquo; personal information will be anonymized and replaced with code for confidentiality during data collection. All data will be kept confidential, with electronic data secured on a password-protected server and paper data stored in locked cabinets. Access to clinical data will be restricted to authorized researchers only. Raw data will be retained for 5 years. The clinical inspectors/monitors will supervise the data collection and control for data completeness and quality.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eQuality control\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eBefore the study begins, the research center will provide standardized training sessions for the entire research team to ensure they follow the study protocol and become familiar with the administration process. Moreover, researchers will receive printed brochures detailing the trial procedures. Clinical researchers are encouraged to contact the research center for assistance if any technical or other issues arise at the clinical site. The research center should promptly provide practical guidance to address these issues. Registered acupuncturists with a minimum of five years of experience will perform the acupuncture treatment. These acupuncturists will undergo training and testing before the trial to ensure consistency in their acupuncture operation. A two-level quality inspection system will be established to ensure the implementation and quality of program. Inspectors at each center will conduct monthly quality examinations, while an independent monitoring team will carry out quality monitoring every three months. After each quality inspection, quality control reports should be submitted to the research center. Furthermore, any modifications to the research protocol must receive approval from the ethics committee.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eSample size calculation\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe sample size for this study was determined based on the responder proportion at the end of a 4-week treatment, with 70.69% for the acupuncture treatment and 55.46% for the itopride treatment, as reported in a previous study [21]. The sample size calculation was performed using PASS 15.0 software, with a 1:1 ratio between the acupuncture plus placebo group and itopride plus sham acupuncture group. A statistical power of 80% (\\u0026beta;=0.2), a one-sided alpha of 0.025 (\\u0026alpha;=0.025), and a non-inferiority margin of -10% (\\u0026Delta;=-10%) were considered in the calculation. The resulting sample size was 57 for each group. Accounting for a 15% dropout rate, each group needed 67 cases, resulting in a total enrollment of 201 cases across three groups.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eStatistical analysis\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eEfficacy analyses will be performed on all random patients based on intention-to-treat principle. Missing data on the primary outcome will be imputed using the multiple imputation method under the missing at-random assumption. If there are significant differences in baseline variables between the two groups, those unbalanced variables will be included as covariates in the analysis of the primary outcome.\\u003c/p\\u003e\\n\\u003cp\\u003eWe will establish confidence intervals at a 95% level, with a significance level set at 0.05. Continuous data will be reported as mean \\u0026plusmn; standard deviation (SD) if it is normally distributed. Otherwise, it will be reported as median (interquartile range). For longitudinal continuous data, we will compare groups using repeated-measures analysis of variance (ANOVA), taking into account both group and time-group interactions. Student\\u0026rsquo;s t-test or Wilcoxon rank-sum test will be used for other continuous data. For categorical data, \\u0026Chi;\\u003csup\\u003e2\\u003c/sup\\u003e test or Fisher\\u0026rsquo;s exact test will be applied as appropriate. The strength of linear relationships between variables will be evaluated using linear correlation analysis, and sensitivity analysis will be performed if required. The occurrence of AEs between groups will be summarized using descriptive analysis.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDissemination Policy\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eWe intend to publish the final trial results in medical journals related to functional gastrointestinal disorder or complementary and alternative medicine (CAM) within 2 years of completing the final data collection.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eThere has been a growing focus in academia on effective treatment for FD in recent years. While some advancements have been achieved in drug treatment for FD [8], the effectiveness is not satisfactory and may come with side effects [9,10]. These problems compel patients to explore other safer and more effective methods in CAM. Acupuncture, a non-pharmacologic therapy in TCM, has been observed to be effective in reliving upper abdominal discomfort and improving QOL in FD patients [13,14]. However, there remains a lack of high-quality clinical studies and evidence supporting the use of acupuncture for FD treatment[8]. This study aims to assess the efficacy and safety of acupuncture for FD in a well-controlled trial design, providing evidence to support the clinical application of acupuncture.\\u003c/p\\u003e\\n\\u003cp\\u003eFor better clinical management, the Rome Ⅲ Consensus proposed a symptom subtype classification of FD, and Rome Ⅳ Consensus adhered to this method [\\u003csup\\u003e28\\u003c/sup\\u003e]. Although it remains controversial whether there is any difference in pathogenesis between PDS and EPS [\\u003csup\\u003e29\\u003c/sup\\u003e], choosing a treatment plan based on FD subtypes has become a new trend [\\u003csup\\u003e30\\u003c/sup\\u003e]. Evidence shows that PDS is the most prominent subtype, affecting more than 60% of all FD patients [3,4]. Therefore, we selected PDS patients as the subjects of this study and diagnosed FD-PDS patients based on Rome Ⅳ criteria. Though multiple mechanisms contribute to PDS development, gastric sensorimotor function disorder has been considered a vital factors [30]. Prokinetic agents have been recommended as the first-choice treatment for PDS patients in a Chinese consensus [\\u003csup\\u003e31\\u003c/sup\\u003e]. Itopride is a prokinetic agent with a response rate of 55%-73% in treating FD and minimal side effects [11,\\u003csup\\u003e32\\u003c/sup\\u003e,\\u003csup\\u003e33\\u003c/sup\\u003e]. Therefore, we used itopride as a positive drug to evaluate the efficacy of acupuncture in treating PDS, thereby providing more clinical treatment decision-making references.\\u003c/p\\u003e\\n\\u003cp\\u003eFive acupoints are selected in this protocol based on findings from clinical and basic research: Sibai (ST2), Zusanli (ST36), Liangmen (ST21), Neiguan (PC6), and Gongsun (SP4). A previous clinical study has shown that acupuncture at above five acupoints can further alleviate discomfort in upper abdominal and improve patients\\u0026rsquo; QOL based on mosapride treatment [\\u003csup\\u003e34\\u003c/sup\\u003e]. ST2, ST36, and ST21 belong to the Yangming stomach meridian of the foot, commonly applied in digestive-system diseases. These three acupoints can regulate the disturbed qi and blood and normalize spleen and stomach function. In particular, acupuncture at ST36 has been proven to improve the gastric function of FD model rats by reducing low-grade inflammation of duodenal mucosal, accelerating gastric emptying, and reducing gut visceral hypersensitivity [\\u003csup\\u003e35\\u003c/sup\\u003e,\\u003csup\\u003e36\\u003c/sup\\u003e]. PC6 and SP4 are both Ba-mai Jiao-hui points. The traditional meridian theory believes that stimulating PC6 and SP4 can positively affect the gastrointestinal tract function and emotional state. Our previous basic studies indicated that acupuncture at PC6 and SP4 could improve gastrointestinal motility disorders, visceral hypersensitivity, and the anxiety and depression-like behavior in rats with FD [\\u003csup\\u003e37\\u003c/sup\\u003e,\\u003csup\\u003e38\\u003c/sup\\u003e]. Therefore, we selected ST2, ST36, ST21, PC6, and SP4 as our acupuncture acupoints.\\u003c/p\\u003e\\n\\u003cp\\u003eTo our knowledge, this is the first multicentre, randomized, double-dummy, single-blind, active-controlled trial on the efficacy and safety of acupuncture for treating PDS. The physical nature of acupuncture treatment poses challenges to the design of sham acupuncture. Nonetheless, researchers use a variety of methods to achieve the placebo effect of acupuncture, including regular needling on non-points, shallow needling on points or non-points, and nonpenetrating needling based on various devices [\\u003csup\\u003e39\\u003c/sup\\u003e]. It is reported that different sham acupuncture treatments can produce different placebo effects of varying sizes [\\u003csup\\u003e40\\u003c/sup\\u003e]. A previous study related to pain relief from acupuncture found that the placebo effect of shallow puncture at non-points is much smaller than shallow puncture at point, deep puncture at nonacupoints, and nonpenetration acupuncture [\\u003csup\\u003e41\\u003c/sup\\u003e]. Ma et al. and Jing et al. reported a significant difference in improving symptoms and QOL among FD patients between regular acupuncture and shallow puncture at non-points [11,21]. Therefore, sham acupuncture was administrated by a shallow puncture at non-points in this trial. Besides proper blinding, we also apply strict quality control measures, blind outcome assessment, concealed treatment allocation, and intention-to-treat analysis to minimize bias and increase the credibility of the results.\\u003c/p\\u003e\\n\\u003cp\\u003eHowever, several limitations of this trial should be noted. Although participants and assessors were blinded in this trial, treatment personnel can not be further blinded due to the inherent nature of acupuncture. Therefore, it cannot be ruled out that performance bias influences the results. Second, this trial only includes patients from Changsha City; whether the results can be applied to other populations or regions requires further research. Finally, we designed a standardized acupuncture regimen without considering individual differences among patients, which may limit the efficacy of acupuncture.\\u003c/p\\u003e\\n\\u003cp\\u003eTo summarize, the outcome of this study aims to validate the effectiveness and safety disparity between acupuncture and Itopride in treating PDS. These results will serve as a dependable foundation to endorse the practical use of acupuncture in managing FD.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTrial status\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis clinical trial has yet to start. Recruitment is scheduled to begin in September 2024 and be completed by December 2026.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cp\\u003eFD = Functional dyspepsia; EPS = epigastric pain syndrome; PDS = postpandial distress syndrome; TCM = Traditional Chinese Medicine; SPIRIT = Standard Protocol Items: Recommendations for Interventional Trials; STRICTA = Standards for Reporting Interventions in Controlled Trials of Acupuncture; QOL = quality of life; PR = proportion of responders; AR = adequate relief; NDSI = Nepean Dyspepsia Symptom Index; SF-NDLQI = The Short Form-Nepean Despepsia Life Quality Index; HADS = Hospital Anxiety and Depression Scale; ETS = The Expectation for Treatment Scale; AEs = Adverse events; CRF = case reported form; SD = standard deviation; ANOVA = one-way analysis of variance; CAM = complementary and alternative medicine.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgments\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eWe would like to thank the patients and researchers who participated in the study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthor contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eMi Liu is the principal investigator of this trial and is fully responsible for the design and implementation. Mi Liu and Geshu Du collaborated on designing a preliminary study protocol, which included the study\\u0026rsquo;s purpose, grouping, and outcomes. Zhimiao Murong and Mailan Liu calculated the sample size and selected suitable statistical methods. Zhaobo Yan and Xuan Xu were responsible for writing the first draft of the manuscript. Huan Zhong and Haolong He were in charge of revising the protocol manuscript. Rong Luo, Weiai Liu, and Geshu Du provided technical and methodological support. All authors read and approved the final manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis research was funded by the Hunan Province TCM Science and Technology Plan Project (No.C2022027, No.D2022005), the National Natural Science Foundation of China (No. 81904097, No. 82374598), the Hunan Provincial Department of Education Funding for Scientific Research Project (No.21A0235, No.23A0284), the National Administration of Traditional Chinese Medicine 2022 Young Qihang Scholar Training Project (State Administration of Traditional Chinese Medicine Letter [2022] No. 256), the Hunan Province Natural Science Project (No.2023JJ30457), the Key Research Project of Health High-level Talents of Hunan Province (No.R2023141), the General Project of Hunan Provincial Health Commission (No.W20243084), the Changsha Natural Science Foundation Project (No.kq2208183), and the Postgraduate Research Innovation Program of Hunan Province (No. QL20220188).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and materials\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eDetails of this study are available from the corresponding author upon request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe research methodology followed the ethical standards stated in the Declaration of Helsinki. It also adhered to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines and the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) checklist. The study protocol obtained approval from the Medical Ethics Committee of the Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine (No. 2023-KY-22). Furthermore, it was registered with the Chinese Clinical Trial Registry (ChiCTR2300068001). All patients were well informed and signed an informed consent form before enrollment.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConflict of interest\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare no conflict of interest.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eOshima T. 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Zhen Ci Yan Jiu. 2023;48(10):1048-54.\\u003c/li\\u003e\\n\\u003cli\\u003eLi DD, Yue ZH, Xu LC, Xie T, Hu GZ, Yang J. Clinical evaluation study on long-term effect of acupuncture with pattern/syndrome differentiation on functional dyspepsia [in Chinese]. Chin Acupunct \\u0026amp; Mox. 2014;34(5):431-434. \\u003c/li\\u003e\\n\\u003cli\\u003eXu Fan. The Clinical Study on the Treatment of Functional Dyspepsia of Disharmony of liver and Stomach with Acupuncture Therapy by dispersing the Stagnated liver-Qi and Regulating the Spirit [master\\u0026rsquo;s thesis]. Chengdu, China: Chengdu University Of Chinese Medicine; 2021.\\u003c/li\\u003e\\n\\u003cli\\u003eChan AW, Tetzlaff JM, Altman DG, Laupacis A, G\\u0026oslash;tzsche PC, A-Jerić KK, et al. SPIRIT 2013 Statement: defining standard protocol items for clinical trials. Rev Panam SaludPublica. 2015;38(6):506-14. \\u003c/li\\u003e\\n\\u003cli\\u003eMacPherson H, Altman DG, Hammerschlag R, Youping L, Taixiang W, White A, et al. Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): extending the CONSORT statement. J Altern Complement Med. 2010;16(10):ST1-14.\\u003c/li\\u003e\\n\\u003cli\\u003eYang JW, Wang LQ, Zou X, Yan SY, Wang Y, Zhao JJ, et al. Effect of Acupuncture for Postprandial Distress Syndrome: A Randomized Clinical Trial. Ann Intern Med. 2020;172(12):777-85.\\u003c/li\\u003e\\n\\u003cli\\u003eTian XP, Li Y, Liang FR, Sun GJ, Yan J, Chang X R, et al. Translation and validation ofthe Nepean Dyspepsia Index for functional dyspepsia in China. World J Gastroenterol. 2009;15(25):3173-77.\\u003c/li\\u003e\\n\\u003cli\\u003eTalley NJ, Verlinden M, Jones M. Quality of life in functional dyspepsia: responsiveness of the Nepean Dyspepsia Index and development of a new 10-item short form. Aliment Pharmacol Ther. 2001;15(2):207-16.\\u003c/li\\u003e\\n\\u003cli\\u003eLloyd M, Sugden N, Thomas M, McGrath A, Skilbeck C. The structure of the Hospital Anxiety and Depression Scale: Theoretical and methodological considerations. Br J Psychol. 2023;114(2):457-75. \\u003c/li\\u003e\\n\\u003cli\\u003eHatch R, Young D, Barber V, Griffiths J, Harrison DA, Watkinson P. Anxiety, Depression and Post Traumatic Stress Disorder after critical illness: a UK-wide prospective cohort study. Crit Care. 2018;22(1):310.\\u003c/li\\u003e\\n\\u003cli\\u003eBeekman E,Verhagen A. Clinimetrics: Hospital Anxiety and Depression Scale. J Physiother. 2018;64(3):198.\\u003c/li\\u003e\\n\\u003cli\\u003eBarth J, Kern A, L\\u0026uuml;thi S, Witt CM. Assessment of patients\\u0026apos; expectations: developmentand validation of the Expectation for Treatment Scale (ETS). BMJ Open. 2019;9(6):e026712.\\u003c/li\\u003e\\n\\u003cli\\u003eVan den Houte K, Carbone F, Goelen N, Schol J, Masuy I, Arts J, et al. Effects of Rome IV Definitions of Functional Dyspepsia Subgroups in Secondary Care. Clin Gastroenterol Hepatol. 2021;19(8):1620-26. \\u003c/li\\u003e\\n\\u003cli\\u003eFang YJ, Liou JM, Chen CC, Lee JY, Hsu YC, Chen MJ, et al. Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria. Gut. 2015;64(10):1517-28.\\u003c/li\\u003e\\n\\u003cli\\u003eVan Den Houte K,Carbone F,Tack J. Postprandial distress syndrome: stratification and management. Expert Rev Gastroenterol Hepatol. 2019;13(1):37-46.\\u003c/li\\u003e\\n\\u003cli\\u003eGastrointestinal Dynamics Group, Chinese Society of Gastroenterology, Chinese Medical Association, Functional Gastrointestinal Disease Collaborative Group, Chinese Society of Gastroenterology, Chinese Medical Association. 2022 expert consensus on diagnosis and treatment of functional dyspepsia in China. Chinese Journal of Digestion, 2019;43(07):433-66.\\u003c/li\\u003e\\n\\u003cli\\u003eHoltmann G, Talley NJ, Liebregts T, Adam B, Parow C. A placebo-controlled trial of itopride in functional dyspepsia. N Engl J Med. 2006;354(8):832-40. \\u003c/li\\u003e\\n\\u003cli\\u003eTalley NJ, Tack J, Ptak T, Gupta R, Gigu\\u0026egrave;re M. Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials. Gut. 2008;57(6):740-46.\\u003c/li\\u003e\\n\\u003cli\\u003eYe Y, Zhu LB, Tan YG. Therapeutic Observation of Three-segment Point Selection plus Mosapride for Functional Dyspepsia [in Chinese]. Shanghai J Acu-mox. 2018;37(10):1136-39.\\u003c/li\\u003e\\n\\u003cli\\u003eDong JZ, Rong PJ, Wang XT, Wang D, Leng MH, Xiao LJ. Effect of electroacupuncture at \\u0026quot;Zusanli\\u0026quot; (ST 36) on duodenal mast cells, NGF and NTRK1 in rats with functional dyspepsia [in Chinese]. Zhongguo Zhen Jiu. 2022;42(7):767-72.\\u003c/li\\u003e\\n\\u003cli\\u003eDong JZ, Rong PJ, Ma TM, Wang D, Wang XT, Qiao Y. Influence of electroacupuncture of\\u0026quot;Zusanli\\u0026quot;(ST36)on mast cells/TRPV1 signaling pathway in visceral hypersensitivity rats with functional dyspepsia [in Chinese]. Zhen Ci Yan Jiu. 2022;47(7):592-7.\\u003c/li\\u003e\\n\\u003cli\\u003eWu PX, Jiang Y, Qin SM, Xing BW, Shi HB, Xie YF, et al. Effects of electroacupuncture on the hypothalamic CRF and its receptors CRF1 and CRF2 in FD rats at theeight confluenence points Neiguan (PC6) and Gongsun (SP4) [in Chinese]. CJTCMP.2023;38(7):3343-46.\\u003c/li\\u003e\\n\\u003cli\\u003eXie YF, Tan SM, Zhan LF, Xing BW, Liu WA. Effects of electroacupuncture at Neiguan and Gongsun acupoints on spleen index and thymus index of FD model rats [in Chinese]. Clin J Chin Med. 2023;15(15):104-7. \\u003c/li\\u003e\\n\\u003cli\\u003eBirch S, Lee MS, Kim TH, Alraek T. Historical perspectives on using sham acupuncture in acupuncture clinical trials. Integr Med Res. 2022;11(1):100725.\\u003c/li\\u003e\\n\\u003cli\\u003eXiong ZY, Liu XY, Ma PH, Sun CY, Sun CY, Liu TL, et al. Placebo Response among Different Types of Sham Acupuncture for Low Back Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Chin J Integr Med. 2023;29(10):941-50.\\u003c/li\\u003e\\n\\u003cli\\u003eZeng D, Yan XX, Deng HM, Li JM, Xiao JX, Yuan JW, et al. Placebo response varies between different types of sham acupuncture: A randomized double-blind trial in neck pain patients. Eur J Pain. 2022;26(5):1006-20.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eTable\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003e1\\u003c/strong\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003eLocations and manipulations of acupoints\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"566\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"19.6113074204947%\\\" colspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eAcupoint\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"28.268551236749115%\\\"\\u003e\\n \\u003cp\\u003eLocation\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"28.79858657243816%\\\"\\u003e\\n \\u003cp\\u003eDepth of needle penetration\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"23.32155477031802%\\\"\\u003e\\n \\u003cp\\u003eManipulation\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"11.307420494699647%\\\" rowspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eSibai\\u003c/p\\u003e\\n \\u003cp\\u003e(ST2)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"8.303886925795053%\\\"\\u003e\\n \\u003cp\\u003eRA1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"28.268551236749115%\\\"\\u003e\\n \\u003cp\\u003eIn the face, directly below the pupil,\\u0026nbsp;and in the depression of the infraorbital foramen.\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"28.79858657243816%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;Inserted perpendicularly at 0.5 cun with 0.20mm*13mm acupuncture needles. \\u0026nbsp; \\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"23.32155477031802%\\\"\\u003e\\n \\u003cp\\u003eElicit de-qi sensation by manual stimulation.\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"9.362549800796813%\\\"\\u003e\\n \\u003cp\\u003eNA1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"31.872509960159363%\\\"\\u003e\\n \\u003cp\\u003eIn the face, 1 cun horizontally next to Sibai.\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"32.47011952191235%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;Inserted perpendicularly at 0.3 cm with 0.20mm*13mm acupuncture needles.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"26.294820717131476%\\\"\\u003e\\n \\u003cp\\u003eWithout manipulation, avoid de-qi sensation.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"11.307420494699647%\\\" rowspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eLiangmen\\u003c/p\\u003e\\n \\u003cp\\u003e(ST21)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"8.303886925795053%\\\"\\u003e\\n \\u003cp\\u003eRA2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"28.268551236749115%\\\"\\u003e\\n \\u003cp\\u003eIn the abdomen,\\u0026nbsp;4 cun\\u0026nbsp;above\\u0026nbsp;the umbilicus,\\u0026nbsp;and 2 cun lateral to the anterior midline.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"28.79858657243816%\\\"\\u003e\\n \\u003cp\\u003eInserted perpendicularly at 0.8-1.2 cun with 0.3mm*40mm acupuncture needles.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"23.32155477031802%\\\"\\u003e\\n \\u003cp\\u003eElicit de-qi sensation by manual stimulation.\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"9.362549800796813%\\\"\\u003e\\n \\u003cp\\u003eNA2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"31.872509960159363%\\\"\\u003e\\n \\u003cp\\u003eIn the abdomen, 2 cun horizontally next to Liangmen.\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"32.47011952191235%\\\"\\u003e\\n \\u003cp\\u003eInserted perpendicularly at 0.5 cm with 0.3mm*40mm acupuncture needles.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"26.294820717131476%\\\"\\u003e\\n \\u003cp\\u003eWithout manipulation, avoid de-qi sensation.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"11.307420494699647%\\\" rowspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eNeiguan\\u003c/p\\u003e\\n \\u003cp\\u003e(PC6)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"8.303886925795053%\\\"\\u003e\\n \\u003cp\\u003eRA3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"28.268551236749115%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;In the flexor aspect of the forearm, between the tendons of palmaris longus and flexor carpi radialis, 2 cun above the transverse crease of the wrist.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"28.79858657243816%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;Inserted perpendicularly at 0.5-1 cun with 0.30mm*25mm acupuncture needles.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"23.32155477031802%\\\"\\u003e\\n \\u003cp\\u003eElicit de-qi sensation by manual stimulation.\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"9.362549800796813%\\\"\\u003e\\n \\u003cp\\u003eNA3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"31.872509960159363%\\\"\\u003e\\n \\u003cp\\u003eIn the midpoint of the line connecting Lingdao (HT4) and Xiaohai (SI8) on the inner side of the forearm.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"32.47011952191235%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;Inserted perpendicularly at 0.3 cm with 0.30mm*25mm acupuncture needles.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"26.294820717131476%\\\"\\u003e\\n \\u003cp\\u003eWithout manipulation, avoid de-qi sensation.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"11.307420494699647%\\\" rowspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eZusanli\\u003c/p\\u003e\\n \\u003cp\\u003e(ST36)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"8.303886925795053%\\\"\\u003e\\n \\u003cp\\u003eRA4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"28.268551236749115%\\\"\\u003e\\n \\u003cp\\u003eIn the anterior aspect of the lower leg, 3 cun directly below Dubi (ST35), and one finger-breadth lateral to the anterior border of the tibia.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"28.79858657243816%\\\"\\u003e\\n \\u003cp\\u003eInserted perpendicularly at 1-2 cun with 0.3mm*40mm acupuncture needles\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"23.32155477031802%\\\"\\u003e\\n \\u003cp\\u003eElicit de-qi sensation by manual stimulation.\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"9.362549800796813%\\\"\\u003e\\n \\u003cp\\u003eNA4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"31.872509960159363%\\\"\\u003e\\n \\u003cp\\u003eIn the anterior aspect of the lower leg, the midpoint of the line connecting Zusanli (ST36) and Yangjiao (GB35).\\u003c/p\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"32.47011952191235%\\\"\\u003e\\n \\u003cp\\u003eInserted perpendicularly at 0.5 cm with 0.3mm*40mm acupuncture needles\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"26.294820717131476%\\\"\\u003e\\n \\u003cp\\u003eWithout manipulation, avoid de-qi sensation.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"11.307420494699647%\\\" rowspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003eGongsun\\u003c/p\\u003e\\n \\u003cp\\u003e(SP4)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"8.303886925795053%\\\"\\u003e\\n \\u003cp\\u003eRA5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"28.268551236749115%\\\"\\u003e\\n \\u003cp\\u003eIn the anterior and inferior of the base of the first metatarsal bone, and on the dorso-ventral boundary.\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"28.79858657243816%\\\"\\u003e\\n \\u003cp\\u003eInserted perpendicularly at 0.5-1 cun with 0.30mm*25mm acupuncture needles\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"23.32155477031802%\\\"\\u003e\\n \\u003cp\\u003eElicit de-qi sensation by manual stimulation.\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"9.362549800796813%\\\"\\u003e\\n \\u003cp\\u003eNA5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"31.872509960159363%\\\"\\u003e\\n \\u003cp\\u003eIn the dorsum of the foot,\\u0026nbsp;the midpoint of the line connecting Gongsun (SP4) and Zhongfeng (LR4).\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"32.47011952191235%\\\"\\u003e\\n \\u003cp\\u003eInserted perpendicularly at 0.3 cm with 0.30mm*25mm acupuncture needles.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"26.294820717131476%\\\"\\u003e\\n \\u003cp\\u003eWithout manipulation, avoid de-qi sensation.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e1 cun is defined as the width of the interphalangeal joint of the patient\\u0026apos;s thumb.\\u003c/p\\u003e\\n\\u003cp\\u003eDubi (ST35) is in the lateral depression of the patellar ligament when the knee is flexed.\\u003c/p\\u003e\\n\\u003cp\\u003eLingdao (HT4) is located on the anteromedial aspect of the wrist, radial to the flexor carpi ulnaris tendon, 1.5 cun above the transverse striation of the wrist.\\u003c/p\\u003e\\n\\u003cp\\u003eXiaohai (SI8) is located in the depression between the ulna\\u0026apos;s olecranon and the humerus\\u0026apos;s medial epicondyle.\\u003c/p\\u003e\\n\\u003cp\\u003eYangjiao (GB35) is located at the lateral legs, 7 cun above the lateral malleolus tip, at the posterior margin of the fibula.\\u003c/p\\u003e\\n\\u003cp\\u003eZhongfeng (LR4) is located at the anterior medial malleolus, in the depression on the medial edge of the tibialis anterior tendon.\\u003c/p\\u003e\\n\\u003cp\\u003eRA: real acupoints; NA: non-acupoints.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 2\\u0026nbsp;\\u003c/strong\\u003e SPIRIT figure for the schedule of enrollment, interventions, and assessments.\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"630\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"24.126984126984127%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"75.87301587301587%\\\" colspan=\\\"9\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSTUDY PERIOD\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"24.126984126984127%\\\" valign=\\\"bottom\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"13.174603174603174%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eEnrolment\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"13.015873015873016%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAllocation\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"30.158730158730158%\\\" colspan=\\\"4\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eTreatment phase\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"19.523809523809526%\\\" colspan=\\\"3\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eFollow-up\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"24.126984126984127%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eTIMEPOINT**\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"26.19047619047619%\\\" colspan=\\\"2\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e1w\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"8.095238095238095%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e2w\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"7.777777777777778%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e3w\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.825396825396825%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e4w\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"7.4603174603174605%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e5w\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.507936507936508%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e9w\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.666666666666667%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e13w\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.349206349206349%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003e17w\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"24.126984126984127%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eENROLMENT:\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"13.174603174603174%\\\" valign=\\\"bottom\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"13.015873015873016%\\\" valign=\\\"bottom\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"8.095238095238095%\\\" valign=\\\"bottom\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"7.777777777777778%\\\" valign=\\\"bottom\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.825396825396825%\\\" valign=\\\"bottom\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"7.4603174603174605%\\\" valign=\\\"bottom\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.507936507936508%\\\" valign=\\\"bottom\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.666666666666667%\\\" valign=\\\"bottom\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.349206349206349%\\\" valign=\\\"bottom\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"24.126984126984127%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eEligibility screen\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"13.174603174603174%\\\"\\u003e\\n \\u003cp\\u003eX\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"13.015873015873016%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"8.095238095238095%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"7.777777777777778%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.825396825396825%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"7.4603174603174605%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.507936507936508%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.666666666666667%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.349206349206349%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"24.126984126984127%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eInformed consent\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"13.174603174603174%\\\"\\u003e\\n \\u003cp\\u003eX\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"13.015873015873016%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"8.095238095238095%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"7.777777777777778%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.825396825396825%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"7.4603174603174605%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.507936507936508%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.666666666666667%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.349206349206349%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"24.126984126984127%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAllocation\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"13.174603174603174%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"13.015873015873016%\\\"\\u003e\\n \\u003cp\\u003eX\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"8.095238095238095%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"7.777777777777778%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.825396825396825%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"7.4603174603174605%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.507936507936508%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"6.666666666666667%\\\"\\u003e\\n 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FD-QOL = functional dyspepsia-related quality of life; HADS = Hospital Anxiety and Depression Scale.\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"acupuncture, clinical trial, functional dyspepsia, acupuncture therapy\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-4347152/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-4347152/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eIntroduction\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePostprandial distress syndrome (PDS) is the prominent subtype in patients with functional dyspepsia (FD) and currently lacks a satisfactory treatment. Acupuncture has become a promising alternative and complementary therapy for managing FD. However, high-level clinical evidence supporting the use of acupuncture for FD is limited.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis study is a multicentre, double-dummy, single-blind, randomized, active-controlled trial. Two hundred and one eligible participants will be randomly assigned into three groups: an acupuncture plus placebo group, an itopride plus sham acupuncture group, and a sham acupuncture plus placebo group. This study consists of a 1-week screening period, a 4-week treatment period, and a 12-week follow-up period. During the intervention period, participants will receive 12 sessions of verum or sham acupuncture treatment (one session per day, three sessions per week, for 4 weeks) along with 50 mg itopride tablets or 50 mg itopride placebo tablets 3 times a day for 20 days (5 continual days a week for 4 weeks). The response rate (patients who had adequate relief of gastric symptoms were considered positive responders) and the elimination rate of cardinal symptoms (postprandial fullness and early satiation) are the primary indicators to evaluate the overall acupuncture effect for PDS. Secondary outcome measures will include the Nepean Dyspepsia Symptom Index (NDSI), the short form-Nepean Dyspepsia Life Quality Index (SF-LQI), and the Hospital Anxiety and Depression Scale (HADS). Participants’ expectations towards acupuncture treatment will also be assessed, and adverse events will be recorded for safety assessment. All analyses will adhere to an intention-to-treat principle.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDiscussion\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eIn conclusion, this trial will determine the efficacy and safety of acupuncture for PDS and provide more high-level evidence to support its application in treating FD.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTrial registration\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eChinese Clinical Trial Registry ChiCTR2300068001. Registered on 2 February 2023.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Effect of acupuncture in patients with postprandial distress syndrome: a multicentre, single-blind, double-dummy, active-controlled, randomized, clinical trial\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-05-14 17:52:31\",\"doi\":\"10.21203/rs.3.rs-4347152/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"378b39ed-d3a6-4290-b1c2-cf50ccb11f9d\",\"owner\":[],\"postedDate\":\"May 14th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-10-29T23:08:10+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-05-14 17:52:31\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-4347152\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-4347152\",\"identity\":\"rs-4347152\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}