Auricular acupressure to improve Oxaliplatin-induced peripheral neuropathy and quality of life: protocol for a randomized controlled trial

Auricular acupressure to improve Oxaliplatin-induced peripheral neuropathy and quality of life: protocol for a randomized controlled 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 Research Article Auricular acupressure to improve Oxaliplatin-induced peripheral neuropathy and quality of life: protocol for a randomized controlled trial Tsui-Ju Chang, Mei-Ling Yeh, Albert Lou Yeh, Ashley Lee Kuo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3974242/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 Purpose Oxaliplatin-induced peripheral neuropathy (OIPN) is a common adverse effect that worsens with increased drug accumulation, affecting patients’ daily activities and quality of life. This study will evaluate the immediate and carry-over effects of auricular acupressure on chronic (OIPN) symptoms, OIPN pain, and quality of life in patients with colorectal cancer. Methods This randomized controlled trial will recruit 76 participants with OIPN. The experimental group will receive auricular acupressure for eight weeks, while the control group will receive standard care. The outcomes will be assessed using an OIPN assessment tool, the Neuropathic Pain Symptom Inventory, a pain visual analogue scale, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Data will be collected before the intervention, biweekly during the intervention, two weeks after the intervention, and one month after the end of the chemotherapy course. Conclusions This study will determine the intervention effects of the 8-week auricular acupressure that alleviates OIPN symptoms and pain in patients with colorectal cancer and enhances their quality of life. The protocol design offers a standardized process that can serve as a reference for current and future studies and accumulate clinical experience regarding implementing auricular acupressure interventions. Auricular acupressure Chemotherapy Colorectal cancer Oxaliplatin-induced Peripheral neuropathy (OIPN) Pain Quality of life Figures Figure 1 Figure 2 Introduction Colorectal cancer has the third highest incidence rate of cancer in the world (10%) and is the second leading cause of cancer-related deaths (10.9%), as reported by the World Health Organization's mortality database [ 1 ]. In Taiwan, the situation is even worse, with colorectal cancer being the most common cancer (38.4%) and the third leading cause of cancer-related deaths (14.6%) in the country [ 2 ]. The current incidence and mortality rates are 30.11% and 5.73% higher than those in 2006, respectively [ 2 ]. These continual increases over the past decade highlight the importance of addressing colorectal cancer as a significant health concern that is affecting the lives and health of many people. A typical adjuvant therapy for colorectal cancer is chemotherapy with oxaliplatin combined with fluorouracil/leucovorin [ 3 ]. This effectively prevents the disease’s progression, increases the response to treatment, and increases the predicted 5-year overall survival rate to 81% [ 4 ]. However, oxaliplatin can cause neurotoxicity, which means damage to the nervous system [ 5 ], and approximately 74.9% of cancer patients experience chronic oxaliplatin-induced peripheral neuropathy (OIPN) [ 6 ]. OIPN symptoms include persistent and excessive numbness, burning sensations, tingling, and pain (unbearable bilateral, distal extremity, and symmetrical) [ 5 , 7 ]. Of these 74.9% of patients, 49.2% experience OIPN pain [ 6 ]. As oxaliplatin accumulates in the body, the effects of OIPN gradually become more serious [ 6 , 8 ]. These patients frequently experience declines in daily activity, emotional distress, and interpersonal and social interference, all of which negatively affect their quality of life [ 7 , 9 ]. For the management of OIPN symptoms, 15–64.2% of patients with cancer have their treatment dose reduced, and 6–21.4% of patients discontinue chemotherapy, leading to disease deterioration and death [ 8 , 10 ]. OIPN can be relieved with medication such as duloxetine [ 11 ], but the pharmacological remedy still exhibits insufficient clinical efficacy [ 12 ]. Nonpharmacological treatments have been used for thousands of years and have garnered worldwide interest [ 13 , 14 ]. A systematic review confirmed the relief effects of nonpharmacological interventions, particularly acupuncture, for chemotherapy-induced peripheral neuropathy [ 15 ]. Acupuncture may protect neurons from deterioration, promote axonal regrowth in neurodegenerative cases [ 16 ], and improve central neurotransmission for relieving neuropathic pain [ 17 ]. However, needle acupuncture is not entirely free from safety concerns [ 18 ]. Empirical research on auricular acupressure has demonstrated efficacy in clinical practice with few complications [ 18 , 19 ]. Auricular acupressure is a non-invasive, convenient, and easy-to-employ method. One study recorded improvements in peripheral neuropathic symptoms and chemotherapy-induced pain following auricular acupressure, especially in the upper and lower limbs [ 20 ]. Additional systematic reviews have revealed that auricular acupressure contributes to pain management in the general population [ 21 , 22 ] and cancer patients [ 23 ]. Given the insufficient evidence, uncertainty remains regarding the effects of nonpharmacological interventions in relieving OIPN [ 13 ]. This study aimed to design a noninvasive, safe, and convenient 8-week auricular acupressure program and evaluate the intervention’s immediate and carry-over effects on chronic OIPN symptoms, OIPN pain, and quality of life in patients with colorectal cancer. The first objective is to apply auricular acupressure to improve participants’ OIPN symptoms, OIPN pain, and quality of life during the intervention period. This study hypothesizes that during the 8-week auricular acupressure intervention, a marked alleviation of OIPN symptoms and pain and improvement in quality of life will be observed in the experimental group compared with the control group. The second objective is to monitor changes in OIPN symptoms, OIPN pain, and quality of life two weeks after the end of the intervention and one month after the end of the chemotherapy course. At this time, significant alleviation of symptoms is expected to be observed. Methods Study design and participants This study will be a randomized controlled trial in which participants will be randomly assigned to either the experimental group receiving auricular acupressure and standard care or the control group receiving only standard care. An 8-week program for auricular acupressure will be designed, and its immediate and carry-over effects will be assessed. Data collection will occur every two weeks during the intervention period, two weeks after the intervention period, and one month after the end of the chemotherapy course, as shown in Fig. 1 . Patients with colorectal cancer experiencing OIPN will be recruited from the outpatient department of a 3,700-bed medical center in northern Taiwan. Participants must be diagnosed as having colorectal cancer with OIPN, over the age of 20 years, able to communicate, and willing to sign a document of informed consent. Patients with peripheral neuropathic symptoms caused by diabetes mellitus, genetic disease, spinal cord injury, or alcoholism will not be included. Patients with wounds on their ears will also be excluded from the study. G*Power software version 3.1 (Franz, Universität Kiel, Germany) was used to estimate the study sample size. According to data on the use of acupuncture for treating chemotherapy-induced peripheral neuropathy symptoms [ 24 ], the effect size is f = 0.28. The following calculation results were obtained with an analysis of variance F test and a selection of repeated measures: α error probability = 0.05, power = 0.80, number of groups = 2, number of measurements = 7, sample size = 60 patients. To account for a 20% potential participant dropout, this study will include 76 patients, with 38 patients in each group. Randomization To ensure unbiased results, an external research team will handle the randomization process. They will use Random Allocation software version 1.0 (Isfahan University of Medical Sciences, Iran) to generate a random number sequence for the control and experimental groups. The software uses permutations to generate a random sequence of numbers in four sets mathematically. The eligible participants in the sets will be divided equally between the experimental and control groups. Additionally, to ensure confidentiality and prevent preconceived notions, opaque envelopes containing the serial numbers will be used to ensure allocation is based on a predetermined sequence. The sealed envelopes will be stored confidentially in a locked cabinet, and neither the participants nor the professionals will know which groups the participants have been assigned to. To allocate participants, the researcher will open the envelopes sequentially and draw out the number sequence in front of the participants. Eligible participants must keep their group assignments the same during the study. Intervention protocol The auricular acupressure protocol was created following the Standards for Reporting Interventions in Clinical Trial of Acupuncture guidelines [ 25 ]. Auricular acupressure is a treatment method that involves applying pressure to specific auricular acupoints that correspond to areas of symptoms. This method will be done for eight consecutive weeks using six selected acupoints, which are Shenmen (TF4), Sympathesis (AH6a), Subcortex (AT4), Endocrine (CO18), Finger (SF1), and Toe (AH2). The acupoints were chosen based on various studies [ 20 , 22 , 26 , 27 ]. A natural, non-toxic botanical called Vaccaria seeds (Wangbuliuxingzi seeds, Beijing, China) will be used in a seed-embedding method to stimulate the auricular acupoints. Pressing the auricular acupoints will create a subjective de qi sensation of soreness, numbness, or heaviness. It is necessary to take a 2-day break from seed adherence once a week to prevent skin breakdown caused by long-term pressure and adhesive tapes. New seeds will be replaced on acupoints on a different ear each week. Auricular acupressure involves adding pressure to specific acupoints on the auricle. This can have positive benefits for managing chemotherapy-induced peripheral neuropathy symptoms by stimulating the auriculo-vagal afferent pathway [ 20 , 22 , 27 ]. This reduces the brain's perception of discomfort. The selected acupoints have been approved and have expert content validity (index = 0.94) by three attending physicians of traditional Chinese medicine with over ten years of experience in clinical practice. The auricular acupressure location corresponds with the published diagram's guidelines for auricular acupoints [ 28 ], as shown in Fig. 2 . An instruction pamphlet was also created to provide information on the auricular acupuncture procedure. The instruction includes information on the relative content, location of the auricular acupoints, practice procedure, frequency, precautions, practice checklist, and reaction to auricular acupressure. Quality control of the intervention This study will involve administering auricular acupressure intervention to the participants. To ensure the process is executed correctly and consistently, the researcher will receive training in traditional Chinese medicine and nursing. The researcher will also obtain a competence certification in auricular acupressure from three attending physicians of traditional Chinese medicine who have more than ten years of clinical practice experience before starting the study. The researcher will practice the auricular acupressure procedure on a model until they achieve 100% accuracy during training. Intervention procedure Participants in the experimental group will receive auricular acupressure treatment on one ear five days per week for eight weeks. During each session, participants will be in a semi-reclining position as the following steps are taken: The acupoints on the ear will be identified The outer ear, including the earlobe, will be sterilized using 75% alcohol A seed, approximately 0.2 cm in diameter, will be attached to each target acupoint using waterproof adhesive tape with dimensions of 0.8 cm × 0.8 cm For five consecutive days, participants will be instructed to apply pressure to each auricular acupoint using their thumb and index finger for 30 seconds, three times per day (morning, noon, and evening). Participants should avoid putting excessive pressure on the taped seeds. The auricular acupuncture should produce the de qi sensation, but participants should avoid putting excessive pressure on the taped seeds. The taped seeds will be removed from the ear on the morning of the sixth day. The researcher will ensure that each participant follows the protocol accurately and complies with the instructions when renewing the seed adhesive tape. An instructional pamphlet will be provided to participants, which they can use to record their experience and reactions to the auricular acupressure. When pressing the auricular acupoint, de qi sensations or other responses must be recorded. Participants in the control group will receive regular chemotherapy treatment. Outcome measures A structured questionnaire will be utilized to assess the impact of auricular acupressure. The outcome measures will include OIPN symptoms, OIPN pain, and the quality. Standard Terminology Criteria for Adverse Events : The fifth edition of this scale will be employed to measure the severity of peripheral neuropathy symptoms caused by Oxaliplatin chemotherapy [ 29 ]. It evaluates the scoring standard for toxic and adverse reactions caused by chemotherapy. The scale consists of two items: peripheral motor and sensory neuropathies. Each item is scored according to five grades of severity (1 through 5). Grade 1 indicates mild symptoms, Grade 2 indicates moderate, Grade 3 indicates severe but not immediately life-threatening, Grade 4 indicates life-threatening consequences, and Grade 5 indicates death. The kappa was 0.60 and 0.60 respectively for interrater reliability of consensus agreement in present and absent symptoms of this scale [ 30 ]. Chemotherapy-Induced Peripheral Neuropathy Assessment Tool : This tool was developed to measure the symptoms and severity of neuropathic pain [ 31 ]. The 23 items are divided into four parts: symptom severity, degree of trouble symptoms cause, symptom frequency, and degree of symptom interference in daily life. The first part evaluates the severity of symptoms, with each item scored on a scale of 0–10. A score of 0 indicates that the symptoms are not severe at all, and a score of 10 indicates that the symptoms are extremely severe. The second part evaluates the degree of symptom distress. A score of 0 indicates that the symptoms are not distressing at all, and a score of 10 indicates that the symptoms are extremely distressing. The third part evaluates symptom frequency. A score of 0 indicates that symptoms never occur, and a score of 10 indicates that symptoms occur continuously. The fourth part evaluates the interference of symptoms in daily life. A score of 0 indicates no interference, and a score of 10 indicates that the symptoms drastically interfere with the patient’s daily life. The Cronbach’s α was 0.95 for the internal consistency reliability of this questionnaire [ 31 ]. Neuropathic Pain Symptom Inventory : This scale was developed to assess the symptoms and severity of neuropathic pain [ 32 ]. It consists of four parts: spontaneous and persistent pain, spontaneous paroxysmal pain, induced pain, and paraesthesia. A total of 10 items, each scored on a scale of 0–10, are used to indicate pain severity, with 0 indicating no pain and 10 indicating the highest degree of pain. The total score is 100 points, and a higher score represents greater severity of neuropathic pain. The intraclass correlation coefficient was 0.89 for the stability reliability of this tool [ 32 ]. Visual analogue scale (VAS) The VAS for pain developed by Huskisson in 1974 will be employed in this study. Patients will self-assess their pain intensity on the basis of their subjective feelings and current pain state. This scale is scored on a scale of 0–10, with 0 indicating no pain and 10 indicating the most severe pain. The reliability of the VAS is high, as indicated by the correlation coefficients being in the range of 0.97–0.99 [ 33 ]. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 This questionnaire was established by the European Organization for Research and Treatment of Cancer in 1986 to evaluate the overall quality of life of patients with cancer before and after receiving treatment. This questionnaire of 30 items is applicable to patients with any cancer and addresses five functional scales (physical, role, cognitive, emotional, and social functioning), three symptoms (fatigue, pain, and nausea/vomiting), a scale of global health/quality of life, and six single items (dyspnea, loss of appetite, insomnia, constipation, diarrhea and financial difficulties The first 28 items are scored using a 4-point response ranging from 1 (not at all) to 4 (very much). The remaining two items assess overall health status and quality of life on a 7-point scale ranging from 1 (very poor) to 7 (excellent), with a higher total score indicating lower quality of life. Cronbach’s for the internal consistency reliability of this scale was 0.85 [ 34 ]. The patients’ demographic characteristics and disease-related information will be collected. The demographic characteristics will include age, sex, height, weight, level of education, marital status, religious beliefs, occupation, income, smoking, drinking, eating, and exercise habits. The disease-related information will include cancer type, cancer stage, family history of cancer, personal medical history, locations of current peripheral neuropathic symptoms, factors aggravating symptoms of peripheral neuropathy, dose of oxaliplatin, use of painkillers, and healthy food consumption. Study procedures Before conducting this study, the institutional review board of the study hospital must approve it. The study will recruit patients with colorectal cancer who are experiencing OIPN from the oncology outpatient department of a medical center in northern Taiwan. The researcher will explain the study's objectives, intervention process, and confidential data collection methods to each participant verbally and in writing. Informed consent will be obtained from all participants. The participants will be randomly assigned to one of two groups: the experimental group, which will receive auricular acupuncture and standard care for eight weeks, and the control group, which will only receive standard care. The researcher will collect data before the intervention, biweekly during the intervention period, two weeks after the intervention period, and one month after the end of the chemotherapy course. Ethical considerations and data analysis This study was reviewed by the Institutional Review Board of xxxxx xxxx xxxxxxxx Hospital (IRB number: 202001339B0). In the process of recruiting participants, their informed consent will be sought in written form without any effects on their rights or medical treatment. The informed consent document will be developed in accordance with the Declaration of Helsinki and will be obtained from all participants after they have individually received an explanation of the study. An explanation of the research purpose, significance, and process will be provided to all participants in consideration of research ethics and to inform them of their personal rights and interests. They will be made aware that their data will remain confidential and that they are free to withdraw from the study at any time without their medical treatment or care being affected. All data will be collected solely for academic research and will never be disclosed to the public. All data analyses will be performed using SPSS version 22.0 for Windows (IBM SPSS Inc, Chicago, IL, USA). Data coding and statistical analyses will be performed by a statistician blinded to participant allocation. The outcome measures will be expressed as the mean (standard deviation) for continuous data and as a number and percentage for categorical data. Furthermore, inferential statistics comparing results between the experimental and control groups will be analyzed using an independent t-test for means and a chi-square test for frequencies. To account for individual variations, a linear mixed model will be used to analyze repeated measurements for the intervention effect and time effect on the severity of OIPN symptoms, OIPN pain, and quality of life across time periods. All statistical tests will be two-sided, and differences with a P value of < 0.05 will be considered statistically significant. The 95% confidence interval will be presented for the interval estimate of a population parameter. Discussion This study aims to examine the effect of auricular acupressure on patients with colorectal cancer who experience OIPN. The study will be a rigorous, randomized, and controlled trial, with repeated measurements. The auricular acupressure will be applied through a seed-embedding method using natural, non-toxic botanical Vaccaria seeds. This approach is relatively convenient and safe. The study expects to see a positive intervention effect in terms of the severity of OIPN symptoms, intensity of OIPN pain, and improvement in quality of life. The study will also analyze and report any adverse effects of auricular acupressure. Auricular acupressure can provide patients and clinical practitioners with diverse options for managing OIPN symptoms. The findings of this study can also serve as a reference for clinical practitioners treating the same or similar patients in clinical care. Declarations Funding Declaration No funding was received for this study. Declaration of competing interests The authors declare to have no conflict of interest. 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Tofthagen C, McMillan S. C, Kip K. E. Development and psychometric evaluation of the chemotherapy-induced peripheral neuropathy assessment tool. Cancer Nursing 2011;34(4): e10-e20. Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, Rostaing S, Lanteri-Minet M, Collin E, Grisart J, Boureau F. Development and validation of the neuropathic pain symptom inventory. International Association for the Study for Pain 2004;108(3):248-257. Karcioglu O, Topacoglu H, Dikme O, Dikme O. A systematic review of the pain scales in adults: which to use. The American Journal of Emergency Medicine 2018;36(4):707-714. Chuang T. Y, Yeh M. L, Chung Y. C. A nurse facilitated mind-body interactive exercise (Chan-Chuang qigong) improves the health status of non-Hodgkin lymphoma patients receiving chemotherapy: randomized controlled trial. International Journal of Nursing Studies 2017; 69:25-33. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3974242","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":274240578,"identity":"1afb713d-8a6c-467b-9e60-ef190787a903","order_by":0,"name":"Tsui-Ju Chang","email":"","orcid":"","institution":"National Taipei University of Nursing and Health Science","correspondingAuthor":false,"prefix":"","firstName":"Tsui-Ju","middleName":"","lastName":"Chang","suffix":""},{"id":274240579,"identity":"aab2264b-4121-4218-802a-46858abf34a9","order_by":1,"name":"Mei-Ling Yeh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIiWNgGAWjYFACxsYDCQwMciAmM1jgAGEtDSAtxgxsCC2MDYQ0gYxNbCBai257c8OBhztq07fL95g9LvjDIMd3I4H9MQ8eLWZnDjYcSDxzPHdnG4+58cw2BmPJGwmMzXi13EgEamk7lrvhGI+ZNG8DQ+IGkJYcfFruPwRrSTcAaeH5w1BPWMsNRpCWmgSIFjaGBAOCWs6AHXbAcMOxtDJp3jYJw5lnHjbO/oNPy/HjDx/+bKuTNzh8eBvQYTbyfMeTD3ycgUcLFByGMSQYGIiISRCoI0bRKBgFo2AUjFQAAF8qVqRBmyqnAAAAAElFTkSuQmCC","orcid":"","institution":"National Taipei University of Nursing and Health Science","correspondingAuthor":true,"prefix":"","firstName":"Mei-Ling","middleName":"","lastName":"Yeh","suffix":""},{"id":274240580,"identity":"6a021e7a-73dd-433b-b40d-db04cbc2f14a","order_by":2,"name":"Albert Lou Yeh","email":"","orcid":"","institution":"National Taipei University of Nursing and Health Science","correspondingAuthor":false,"prefix":"","firstName":"Albert","middleName":"Lou","lastName":"Yeh","suffix":""},{"id":274240581,"identity":"99d26c8e-8f04-4926-8532-bf69cd89dedd","order_by":3,"name":"Ashley Lee Kuo","email":"","orcid":"","institution":"National Taipei University of Nursing and Health Science","correspondingAuthor":false,"prefix":"","firstName":"Ashley","middleName":"Lee","lastName":"Kuo","suffix":""}],"badges":[],"createdAt":"2024-02-21 02:06:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3974242/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3974242/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51565968,"identity":"1e842def-c7fa-4068-81d4-0e125e7fceec","added_by":"auto","created_at":"2024-02-23 19:10:05","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":660473,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of the study design and participant allocation\u003c/p\u003e\n\u003cp\u003eAbbreviations: CTCAE, Common Terminology Criteria for Adverse Events; CIPNAT, Chemotherapy-Induced Peripheral Neuropathy Assessment Tool; NPSI, Neuropathic Pain Symptom Inventory; VAS, Visual analog scale; European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Core 30\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3974242/v1/bd3ceeb503a4b423177f80f4.png"},{"id":51565969,"identity":"9c1346a9-2a0c-433c-8c74-89b9d826bd26","added_by":"auto","created_at":"2024-02-23 19:10:05","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":257430,"visible":true,"origin":"","legend":"\u003cp\u003eThe precise location of six auricular acupoints for acupressure\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-3974242/v1/eb60b0f8f1151301a1401eb3.png"},{"id":53479514,"identity":"3506d56c-976d-4334-a3c9-aa57e80b4552","added_by":"auto","created_at":"2024-03-26 13:22:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":768809,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3974242/v1/f07dca72-6fcf-43bd-be59-529e56b932a5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Auricular acupressure to improve Oxaliplatin-induced peripheral neuropathy and quality of life: protocol for a randomized controlled trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eColorectal cancer has the third highest incidence rate of cancer in the world (10%) and is the second leading cause of cancer-related deaths (10.9%), as reported by the World Health Organization's mortality database [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In Taiwan, the situation is even worse, with colorectal cancer being the most common cancer (38.4%) and the third leading cause of cancer-related deaths (14.6%) in the country [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The current incidence and mortality rates are 30.11% and 5.73% higher than those in 2006, respectively [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. These continual increases over the past decade highlight the importance of addressing colorectal cancer as a significant health concern that is affecting the lives and health of many people.\u003c/p\u003e \u003cp\u003eA typical adjuvant therapy for colorectal cancer is chemotherapy with oxaliplatin combined with fluorouracil/leucovorin [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. This effectively prevents the disease\u0026rsquo;s progression, increases the response to treatment, and increases the predicted 5-year overall survival rate to 81% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, oxaliplatin can cause neurotoxicity, which means damage to the nervous system [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and approximately 74.9% of cancer patients experience chronic oxaliplatin-induced peripheral neuropathy (OIPN) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. OIPN symptoms include persistent and excessive numbness, burning sensations, tingling, and pain (unbearable bilateral, distal extremity, and symmetrical) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Of these 74.9% of patients, 49.2% experience OIPN pain [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. As oxaliplatin accumulates in the body, the effects of OIPN gradually become more serious [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. These patients frequently experience declines in daily activity, emotional distress, and interpersonal and social interference, all of which negatively affect their quality of life [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. For the management of OIPN symptoms, 15\u0026ndash;64.2% of patients with cancer have their treatment dose reduced, and 6\u0026ndash;21.4% of patients discontinue chemotherapy, leading to disease deterioration and death [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOIPN can be relieved with medication such as duloxetine [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], but the pharmacological remedy still exhibits insufficient clinical efficacy [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Nonpharmacological treatments have been used for thousands of years and have garnered worldwide interest [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. A systematic review confirmed the relief effects of nonpharmacological interventions, particularly acupuncture, for chemotherapy-induced peripheral neuropathy [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Acupuncture may protect neurons from deterioration, promote axonal regrowth in neurodegenerative cases [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], and improve central neurotransmission for relieving neuropathic pain [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, needle acupuncture is not entirely free from safety concerns [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Empirical research on auricular acupressure has demonstrated efficacy in clinical practice with few complications [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Auricular acupressure is a non-invasive, convenient, and easy-to-employ method. One study recorded improvements in peripheral neuropathic symptoms and chemotherapy-induced pain following auricular acupressure, especially in the upper and lower limbs [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Additional systematic reviews have revealed that auricular acupressure contributes to pain management in the general population [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] and cancer patients [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Given the insufficient evidence, uncertainty remains regarding the effects of nonpharmacological interventions in relieving OIPN [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aimed to design a noninvasive, safe, and convenient 8-week auricular acupressure program and evaluate the intervention\u0026rsquo;s immediate and carry-over effects on chronic OIPN symptoms, OIPN pain, and quality of life in patients with colorectal cancer. The first objective is to apply auricular acupressure to improve participants\u0026rsquo; OIPN symptoms, OIPN pain, and quality of life during the intervention period. This study hypothesizes that during the 8-week auricular acupressure intervention, a marked alleviation of OIPN symptoms and pain and improvement in quality of life will be observed in the experimental group compared with the control group. The second objective is to monitor changes in OIPN symptoms, OIPN pain, and quality of life two weeks after the end of the intervention and one month after the end of the chemotherapy course. At this time, significant alleviation of symptoms is expected to be observed.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eThis study will be a randomized controlled trial in which participants will be randomly assigned to either the experimental group receiving auricular acupressure and standard care or the control group receiving only standard care. An 8-week program for auricular acupressure will be designed, and its immediate and carry-over effects will be assessed. Data collection will occur every two weeks during the intervention period, two weeks after the intervention period, and one month after the end of the chemotherapy course, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatients with colorectal cancer experiencing OIPN will be recruited from the outpatient department of a 3,700-bed medical center in northern Taiwan. Participants must be diagnosed as having colorectal cancer with OIPN, over the age of 20 years, able to communicate, and willing to sign a document of informed consent. Patients with peripheral neuropathic symptoms caused by diabetes mellitus, genetic disease, spinal cord injury, or alcoholism will not be included. Patients with wounds on their ears will also be excluded from the study. G*Power software version 3.1 (Franz, Universit\u0026auml;t Kiel, Germany) was used to estimate the study sample size. According to data on the use of acupuncture for treating chemotherapy-induced peripheral neuropathy symptoms [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], the effect size is f\u0026thinsp;=\u0026thinsp;0.28. The following calculation results were obtained with an analysis of variance F test and a selection of repeated measures: α error probability\u0026thinsp;=\u0026thinsp;0.05, power\u0026thinsp;=\u0026thinsp;0.80, number of groups\u0026thinsp;=\u0026thinsp;2, number of measurements\u0026thinsp;=\u0026thinsp;7, sample size\u0026thinsp;=\u0026thinsp;60 patients. To account for a 20% potential participant dropout, this study will include 76 patients, with 38 patients in each group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eRandomization\u003c/h2\u003e \u003cp\u003eTo ensure unbiased results, an external research team will handle the randomization process. They will use Random Allocation software version 1.0 (Isfahan University of Medical Sciences, Iran) to generate a random number sequence for the control and experimental groups. The software uses permutations to generate a random sequence of numbers in four sets mathematically. The eligible participants in the sets will be divided equally between the experimental and control groups. Additionally, to ensure confidentiality and prevent preconceived notions, opaque envelopes containing the serial numbers will be used to ensure allocation is based on a predetermined sequence. The sealed envelopes will be stored confidentially in a locked cabinet, and neither the participants nor the professionals will know which groups the participants have been assigned to. To allocate participants, the researcher will open the envelopes sequentially and draw out the number sequence in front of the participants. Eligible participants must keep their group assignments the same during the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eIntervention protocol\u003c/h2\u003e \u003cp\u003eThe auricular acupressure protocol was created following the Standards for Reporting Interventions in Clinical Trial of Acupuncture guidelines [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Auricular acupressure is a treatment method that involves applying pressure to specific auricular acupoints that correspond to areas of symptoms. This method will be done for eight consecutive weeks using six selected acupoints, which are Shenmen (TF4), Sympathesis (AH6a), Subcortex (AT4), Endocrine (CO18), Finger (SF1), and Toe (AH2). The acupoints were chosen based on various studies [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. A natural, non-toxic botanical called Vaccaria seeds (Wangbuliuxingzi seeds, Beijing, China) will be used in a seed-embedding method to stimulate the auricular acupoints. Pressing the auricular acupoints will create a subjective de qi sensation of soreness, numbness, or heaviness. It is necessary to take a 2-day break from seed adherence once a week to prevent skin breakdown caused by long-term pressure and adhesive tapes. New seeds will be replaced on acupoints on a different ear each week. Auricular acupressure involves adding pressure to specific acupoints on the auricle. This can have positive benefits for managing chemotherapy-induced peripheral neuropathy symptoms by stimulating the auriculo-vagal afferent pathway [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. This reduces the brain's perception of discomfort. The selected acupoints have been approved and have expert content validity (index\u0026thinsp;=\u0026thinsp;0.94) by three attending physicians of traditional Chinese medicine with over ten years of experience in clinical practice. The auricular acupressure location corresponds with the published diagram's guidelines for auricular acupoints [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. An instruction pamphlet was also created to provide information on the auricular acupuncture procedure. The instruction includes information on the relative content, location of the auricular acupoints, practice procedure, frequency, precautions, practice checklist, and reaction to auricular acupressure.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eQuality control of the intervention\u003c/h2\u003e \u003cp\u003eThis study will involve administering auricular acupressure intervention to the participants. To ensure the process is executed correctly and consistently, the researcher will receive training in traditional Chinese medicine and nursing. The researcher will also obtain a competence certification in auricular acupressure from three attending physicians of traditional Chinese medicine who have more than ten years of clinical practice experience before starting the study. The researcher will practice the auricular acupressure procedure on a model until they achieve 100% accuracy during training.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eIntervention procedure\u003c/h2\u003e \u003cp\u003eParticipants in the experimental group will receive auricular acupressure treatment on one ear five days per week for eight weeks. During each session, participants will be in a semi-reclining position as the following steps are taken:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe acupoints on the ear will be identified\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe outer ear, including the earlobe, will be sterilized using 75% alcohol\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eA seed, approximately 0.2 cm in diameter, will be attached to each target acupoint using waterproof adhesive tape with dimensions of 0.8 cm \u0026times; 0.8 cm\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eFor five consecutive days, participants will be instructed to apply pressure to each auricular acupoint using their thumb and index finger for 30 seconds, three times per day (morning, noon, and evening). Participants should avoid putting excessive pressure on the taped seeds.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eThe auricular acupuncture should produce the \u003cem\u003ede qi\u003c/em\u003e sensation, but participants should avoid putting excessive pressure on the taped seeds. The taped seeds will be removed from the ear on the morning of the sixth day. The researcher will ensure that each participant follows the protocol accurately and complies with the instructions when renewing the seed adhesive tape. An instructional pamphlet will be provided to participants, which they can use to record their experience and reactions to the auricular acupressure. When pressing the auricular acupoint, \u003cem\u003ede qi\u003c/em\u003e sensations or other responses must be recorded. Participants in the control group will receive regular chemotherapy treatment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcome measures\u003c/h2\u003e \u003cp\u003eA structured questionnaire will be utilized to assess the impact of auricular acupressure. The outcome measures will include OIPN symptoms, OIPN pain, and the quality.\u003c/p\u003e \u003cp\u003e \u003cem\u003eStandard Terminology Criteria for Adverse Events\u003c/em\u003e: The fifth edition of this scale will be employed to measure the severity of peripheral neuropathy symptoms caused by Oxaliplatin chemotherapy [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. It evaluates the scoring standard for toxic and adverse reactions caused by chemotherapy. The scale consists of two items: peripheral motor and sensory neuropathies. Each item is scored according to five grades of severity (1 through 5). Grade 1 indicates mild symptoms, Grade 2 indicates moderate, Grade 3 indicates severe but not immediately life-threatening, Grade 4 indicates life-threatening consequences, and Grade 5 indicates death. The kappa was 0.60 and 0.60 respectively for interrater reliability of consensus agreement in present and absent symptoms of this scale [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003eChemotherapy-Induced Peripheral Neuropathy Assessment Tool\u003c/em\u003e: This tool was developed to measure the symptoms and severity of neuropathic pain [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The 23 items are divided into four parts: symptom severity, degree of trouble symptoms cause, symptom frequency, and degree of symptom interference in daily life. The first part evaluates the severity of symptoms, with each item scored on a scale of 0\u0026ndash;10. A score of 0 indicates that the symptoms are not severe at all, and a score of 10 indicates that the symptoms are extremely severe. The second part evaluates the degree of symptom distress. A score of 0 indicates that the symptoms are not distressing at all, and a score of 10 indicates that the symptoms are extremely distressing. The third part evaluates symptom frequency. A score of 0 indicates that symptoms never occur, and a score of 10 indicates that symptoms occur continuously. The fourth part evaluates the interference of symptoms in daily life. A score of 0 indicates no interference, and a score of 10 indicates that the symptoms drastically interfere with the patient\u0026rsquo;s daily life. The Cronbach\u0026rsquo;s α was 0.95 for the internal consistency reliability of this questionnaire [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003eNeuropathic Pain Symptom Inventory\u003c/em\u003e: This scale was developed to assess the symptoms and severity of neuropathic pain [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. It consists of four parts: spontaneous and persistent pain, spontaneous paroxysmal pain, induced pain, and paraesthesia. A total of 10 items, each scored on a scale of 0\u0026ndash;10, are used to indicate pain severity, with 0 indicating no pain and 10 indicating the highest degree of pain. The total score is 100 points, and a higher score represents greater severity of neuropathic pain. The intraclass correlation coefficient was 0.89 for the stability reliability of this tool [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eVisual analogue scale (VAS)\u003c/strong\u003e \u003cp\u003eThe VAS for pain developed by Huskisson in 1974 will be employed in this study. Patients will self-assess their pain intensity on the basis of their subjective feelings and current pain state. This scale is scored on a scale of 0\u0026ndash;10, with 0 indicating no pain and 10 indicating the most severe pain. The reliability of the VAS is high, as indicated by the correlation coefficients being in the range of 0.97\u0026ndash;0.99 [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEuropean Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30\u003c/strong\u003e \u003cp\u003eThis questionnaire was established by the European Organization for Research and Treatment of Cancer in 1986 to evaluate the overall quality of life of patients with cancer before and after receiving treatment. This questionnaire of 30 items is applicable to patients with any cancer and addresses five functional scales (physical, role, cognitive, emotional, and social functioning), three symptoms (fatigue, pain, and nausea/vomiting), a scale of global health/quality of life, and six single items (dyspnea, loss of appetite, insomnia, constipation, diarrhea and financial difficulties The first 28 items are scored using a 4-point response ranging from 1 (not at all) to 4 (very much). The remaining two items assess overall health status and quality of life on a 7-point scale ranging from 1 (very poor) to 7 (excellent), with a higher total score indicating lower quality of life. Cronbach\u0026rsquo;s for the internal consistency reliability of this scale was 0.85 [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003c/p\u003e \u003cp\u003eThe patients\u0026rsquo; demographic characteristics and disease-related information will be collected. The demographic characteristics will include age, sex, height, weight, level of education, marital status, religious beliefs, occupation, income, smoking, drinking, eating, and exercise habits. The disease-related information will include cancer type, cancer stage, family history of cancer, personal medical history, locations of current peripheral neuropathic symptoms, factors aggravating symptoms of peripheral neuropathy, dose of oxaliplatin, use of painkillers, and healthy food consumption.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStudy procedures\u003c/h2\u003e \u003cp\u003eBefore conducting this study, the institutional review board of the study hospital must approve it. The study will recruit patients with colorectal cancer who are experiencing OIPN from the oncology outpatient department of a medical center in northern Taiwan. The researcher will explain the study's objectives, intervention process, and confidential data collection methods to each participant verbally and in writing. Informed consent will be obtained from all participants. The participants will be randomly assigned to one of two groups: the experimental group, which will receive auricular acupuncture and standard care for eight weeks, and the control group, which will only receive standard care. The researcher will collect data before the intervention, biweekly during the intervention period, two weeks after the intervention period, and one month after the end of the chemotherapy course.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eEthical considerations and data analysis\u003c/h2\u003e \u003cp\u003eThis study was reviewed by the Institutional Review Board of xxxxx xxxx xxxxxxxx Hospital (IRB number: 202001339B0). In the process of recruiting participants, their informed consent will be sought in written form without any effects on their rights or medical treatment. The informed consent document will be developed in accordance with the Declaration of Helsinki and will be obtained from all participants after they have individually received an explanation of the study. An explanation of the research purpose, significance, and process will be provided to all participants in consideration of research ethics and to inform them of their personal rights and interests. They will be made aware that their data will remain confidential and that they are free to withdraw from the study at any time without their medical treatment or care being affected. All data will be collected solely for academic research and will never be disclosed to the public.\u003c/p\u003e \u003cp\u003eAll data analyses will be performed using SPSS version 22.0 for Windows (IBM SPSS Inc, Chicago, IL, USA). Data coding and statistical analyses will be performed by a statistician blinded to participant allocation. The outcome measures will be expressed as the mean (standard deviation) for continuous data and as a number and percentage for categorical data. Furthermore, inferential statistics comparing results between the experimental and control groups will be analyzed using an independent t-test for means and a chi-square test for frequencies. To account for individual variations, a linear mixed model will be used to analyze repeated measurements for the intervention effect and time effect on the severity of OIPN symptoms, OIPN pain, and quality of life across time periods. All statistical tests will be two-sided, and differences with a P value of \u0026lt;\u0026thinsp;0.05 will be considered statistically significant. The 95% confidence interval will be presented for the interval estimate of a population parameter.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study aims to examine the effect of auricular acupressure on patients with colorectal cancer who experience OIPN. The study will be a rigorous, randomized, and controlled trial, with repeated measurements. The auricular acupressure will be applied through a seed-embedding method using natural, non-toxic botanical Vaccaria seeds. This approach is relatively convenient and safe. The study expects to see a positive intervention effect in terms of the severity of OIPN symptoms, intensity of OIPN pain, and improvement in quality of life. The study will also analyze and report any adverse effects of auricular acupressure. Auricular acupressure can provide patients and clinical practitioners with diverse options for managing OIPN symptoms. The findings of this study can also serve as a reference for clinical practitioners treating the same or similar patients in clinical care.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare to have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTrial Register\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is registered at Clinical Trials.gov (Identifier: NCT04751513).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Health Organization. WHO report on cancer: setting priorities, investing wisely, and providing care for all; 2023.\u003c/li\u003e\n\u003cli\u003eHealth Promotion Administration Ministry of Health and Welfare, Taiwan. Cause of Death Statistics; 2021. \u003c/li\u003e\n\u003cli\u003eNational Comprehensive Cancer Network. NCCN guidelines for patient of colon cancer; 2022.\u003c/li\u003e\n\u003cli\u003eMeyers B. M, Cosby R, Quereshy F, Jonker D. Adjuvant chemotherapy for stage II and III colon cancer following complete resection: a cancer care Ontario systematic review. Clinical Oncology 2017;29(7):459-465.\u003c/li\u003e\n\u003cli\u003eZajaczkowsska R, Kocot-Kepska M, Leppert W, Wrzosek A, Mika J, Wordliczek J. Mechanisms of chemotherapy-induced neuropathy. International Journal of Molecular Sciences 2019;20(6):1451.\u003c/li\u003e\n\u003cli\u003eBrozou V, Vadalouca A, Zis P. Pain in platin-induced neuropathies: a systematic review and meta-analysis. Pain and Therapy 2018;7(1):105-119.\u003c/li\u003e\n\u003cli\u003eBennedsgaard K, Ventzel L, Themistocleous A. C, Bennett D. L, Jensen A. B, Jensen A. R, Andersen N.T, Jensen T. S, Tankisi H, Finnerup N. B. Long-term symptoms of polyneuropathy in breast and colorectal cancer patients treated with and without adjuvant chemotherapy. Cancer Medicine 2020; 9(14):5114-5123.\u003c/li\u003e\n\u003cli\u003eGebremedhn E. G, Shortland P. J, Mahns D. A. The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: a systematic review. BMC Cancer 2018;18(1):410.\u003c/li\u003e\n\u003cli\u003eGaballah A, Shafik A, Elhusseiny K, Ashraf M. Chemotherapy-Induced peripheral neuropathy in Egyptian patients: single institution retrospective analysis. Asian Pacific Journal of Cancer Prevention 2018;19(8):2223-2227. \u003c/li\u003e\n\u003cli\u003eZribi A, Nasr S. B, Hamdi S, Ayari J, Fendri S, Balti M, Haddaooui A.Oxaliplatin-induced peripheral neuropathy risk factors and management in Tunisian population.\u003cem\u003e \u003c/em\u003eThe Pan African Medical Journal 2020; 35:83.\u003c/li\u003e\n\u003cli\u003eHou S, Huh B, Kim H. K, Kim K. H, Abdi S. Treatment of chemotherapy-induced peripheral neuropathy: systematic review and recommendations. Pain Physicians 2018;21(6):571-592.\u003c/li\u003e\n\u003cli\u003eSalat, K. Chemotherapy-induced peripheral neuropathy: Current state of knowledge and perspectives for pharmacotherapy. Pharmacological Reports 2020; 72(3): 486-507.\u003c/li\u003e\n\u003cli\u003eHao J, Zhu X, Bensoussan A. Effects of nonpharmacological interventions in chemotherapy-induced peripheral neuropathy: an overview of systematic reviews and meta-analyses. Integrative Cancer Therapies 2020; 19:1-23.\u003c/li\u003e\n\u003cli\u003eYeh M. L, Lin K. C, Chen H. H, Wang Y. J, Huang Y. C. Use of traditional medicine and complementary and alternative medicine in Taiwan: a multilevel analysis. Holistic Nursing Practice 2015;29(2):87-95.\u003c/li\u003e\n\u003cli\u003eOh P. J, Kim Y. L. Effectiveness of non-pharmacologic interventions in chemotherapy induced peripheral neuropathy: a systematic review and meta-analysis. Journal of Korean Academy of Nursing 2018; 48(2):123-142. \u003c/li\u003e\n\u003cli\u003eLai H. C, Chang Q. Y, Hsieh C. L. Signal transduction pathways of acupuncture for treating some nervous system diseases. Evidence-Based Complementary and Alternative Medicine 2019; 29096329:37.\u003c/li\u003e\n\u003cli\u003eLin J. G, Chen W. L. Acupuncture analgesia: a review of its mechanisms of actions. The American Journal of Chinese Medicine 2008;36(4):635-645.\u003c/li\u003e\n\u003cli\u003eChung Y. C, Chen H. H, Yeh M. L. Acupoint stimulation intervention for people with primary dysmenorrhea: systematic review and meta-analysis of randomized trials. Complementary Therapies in Medicine 2012;20(5):353-363.\u003c/li\u003e\n\u003cli\u003eNielsen A, Gereau S, Tick H. Risks and safety of extended auricular therapy: a review of reviews and case reports of adverse events. Pain Medicine 2020;21(6): 1276-1293.\u003c/li\u003e\n\u003cli\u003eYeh C. H, Lukkahatai N, Campbell C, Sair H, Zhang F, Mensah S, Garry C, Zeng J, Chen C, Pinedo M, Khoshnoodi M, Smith T. J, Saligan L. N. Preliminary effectiveness of auricular point acupressure on chemotherapy-induced neuropathy: part 1 self-reported outcomes. Pain Management Nursing 2019;20(6):614-622.\u003c/li\u003e\n\u003cli\u003eLiu M, Tong Y, Chai L, Chen S, Xue Z, Chen Y, Li X. Effects of auricular point acupressure on pain relief: a systematic review. Pain Management Nursing 2020; S1524-9042(20):30168-5.\u003c/li\u003e\n\u003cli\u003eYou E, Kim D, Harris R, D\u0026rsquo;Alonzo K. Effects of auricular acupressure on pain management: a systematic review.\u003cem\u003e \u003c/em\u003ePain Management Nursing 2019;20(1):17-24.\u003c/li\u003e\n\u003cli\u003eYang Y, Wen J, Hong J. The effects of auricular therapy for cancer pain: a systematic review and meta-analysis. Evidence-Based Complementary and Alternative Medicine 2020; 1618767:10\u003c/li\u003e\n\u003cli\u003eMolassiotis A, Suen L. K. P, Cheng H. L, Mok T. S. K, Lee S. C. Y, Wang C. H, Lee P, Leung H, Chan V, Lau T. K. H, Yeo W. A randomized assessor-blinded wait-list-controlled trial to assess the effectiveness of acupuncture in the management of chemotherapy-induced peripheral neuropathy. Integrative Cancer Therapies 2019; 18:1-12.\u003c/li\u003e\n\u003cli\u003eChen H, Yang M, Ning Z, Lam W. L, Zhao Y. K, Yeung W. F, Ng B. F. L, Ziea E. T. C, Lao L. A guideline for randomized controlled trials of acupuncture. The American Journal of Chinese Medicine 2019;47(1):1-18.\u003c/li\u003e\n\u003cli\u003eChang L, Yang J. Effect of auricular point pressure combined with cancer pain standardized therapy on analgesic effect and treatment compliance of cancer pain patients. The Journal of Smart Healthcare 2019;5(17):71-73.\u003c/li\u003e\n\u003cli\u003eYeh H. C, Lin W. C, Suen L. K. P, Park N. J, Wood L. J, London G. J. V, ovbjerg, D. H. Auricular point acupressure to manage aromatase inhibitor-induced arthralgia in postmenopausal breast cancer survivors: a pilot study. Oncology Nursing Forum 2017;44(4):476-487.\u003c/li\u003e\n\u003cli\u003eChen H. F, Chen K. The clinical figured cards of auricular points. 1st.ed. Beijing: China Book Inc.;2000.\u003c/li\u003e\n\u003cli\u003eNational Cancer Institute. Common terminology criteria for adverse events (CTCAE) version 5; 2022.\u003c/li\u003e\n\u003cli\u003eFairchild A. T, Tanksley J. P, Tenenbaum J. D, Palta M, Hong J. C. Interrater reliability in toxicity identification: limitations of current standards. International Journal of Radiation Oncology. Biology. Physics 2020;107(5):996-1100.\u003c/li\u003e\n\u003cli\u003eTofthagen C, McMillan S. C, Kip K. E. Development and psychometric evaluation of the chemotherapy-induced peripheral neuropathy assessment tool. Cancer Nursing 2011;34(4): e10-e20.\u003c/li\u003e\n\u003cli\u003eBouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, Rostaing S, Lanteri-Minet M, Collin E, Grisart J, Boureau F. Development and validation of the neuropathic pain symptom inventory. International Association for the Study for Pain 2004;108(3):248-257. \u003c/li\u003e\n\u003cli\u003eKarcioglu O, Topacoglu H, Dikme O, Dikme O. A systematic review of the pain scales in adults: which to use. The American Journal of Emergency Medicine 2018;36(4):707-714.\u003c/li\u003e\n\u003cli\u003eChuang T. Y, Yeh M. L, Chung Y. C. A nurse facilitated mind-body interactive exercise (Chan-Chuang qigong) improves the health status of non-Hodgkin lymphoma patients receiving chemotherapy: randomized controlled trial. International Journal of Nursing Studies 2017; 69:25-33. \u003c/li\u003e\n\u003c/ol\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":"[email protected]","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":"Auricular acupressure, Chemotherapy, Colorectal cancer, Oxaliplatin-induced Peripheral neuropathy (OIPN), Pain, Quality of life","lastPublishedDoi":"10.21203/rs.3.rs-3974242/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3974242/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eOxaliplatin-induced peripheral neuropathy (OIPN) is a common adverse effect that worsens with increased drug accumulation, affecting patients\u0026rsquo; daily activities and quality of life. This study will evaluate the immediate and carry-over effects of auricular acupressure on chronic (OIPN) symptoms, OIPN pain, and quality of life in patients with colorectal cancer.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis randomized controlled trial will recruit 76 participants with OIPN. The experimental group will receive auricular acupressure for eight weeks, while the control group will receive standard care. The outcomes will be assessed using an OIPN assessment tool, the Neuropathic Pain Symptom Inventory, a pain visual analogue scale, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Data will be collected before the intervention, biweekly during the intervention, two weeks after the intervention, and one month after the end of the chemotherapy course.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis study will determine the intervention effects of the 8-week auricular acupressure that alleviates OIPN symptoms and pain in patients with colorectal cancer and enhances their quality of life. The protocol design offers a standardized process that can serve as a reference for current and future studies and accumulate clinical experience regarding implementing auricular acupressure interventions.\u003c/p\u003e","manuscriptTitle":"Auricular acupressure to improve Oxaliplatin-induced peripheral neuropathy and quality of life: protocol for a randomized controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-23 19:10:00","doi":"10.21203/rs.3.rs-3974242/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","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":"98ba135a-639e-4b85-84ee-5e900982aa33","owner":[],"postedDate":"February 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-26T13:14:29+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-23 19:10:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3974242","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3974242","identity":"rs-3974242","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}