Efficacy of different doses of Platelet-Rich Plasma for Moderate Carpal Tunnel Syndrome:Study Protocol for a Prospective, Randomized, Controlled trail

Efficacy of different doses of Platelet-Rich Plasma for Moderate Carpal Tunnel Syndrome:Study Protocol for a Prospective, Randomized, Controlled trail | 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 Efficacy of different doses of Platelet-Rich Plasma for Moderate Carpal Tunnel Syndrome:Study Protocol for a Prospective, Randomized, Controlled trail Yuxi Li, Ying Lu, Zhenhai Wei, Zhipeng Li, Mengxia Guo, Guobin Xu, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6534984/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Feb, 2026 Read the published version in Trials → Version 1 posted 5 You are reading this latest preprint version Abstract Background Carpal tunnel syndrome (CTS) is the most prevalent peripheral nerve disorder, with an incidence of approximately 0.4-1% in the general population. Recently, Platelet-rich plasma (PRP) injections attention as an innovative treatment, proving more effective than corticosteroids and dextrose. However, the optimal PRP therapeutic dosage remains unclear. Methods This double-blind, randomized controlled study will include 60 patients with moderate carpal tunnel syndrome. Participants will be randomly assigned to one of two groups: 3ml PRP or 5ml PRP, which will receive two injections 2 weeks apart. Injections are performed by experienced doctors under ultrasound guidance. Primary outcome measures include changes in the Visual Analogue Scale (VAS) of numbness from baseline to six months. Secondary outcomes involve ultrasound parameters (median nerve cross-sectional area, blood flow and swelling rate), Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) score. Sensory nerve conduction velocity (SNCV), distal motor latency (DML) of the median nerve as measured by electromyography. The change of ultrasound images and nerve electrophysiology will be evaluated at baseline and 6-month follow-ups. Beyond that, other outcomes will be evaluated at baseline and 1-month, 3-month and 6-month follow-ups. The final statistical analysis of the data will be finished by using intention-to-treat and per-protocol analysis. Discussion This study aims to assess the efficacy of various doses of PRP injection in moderate CTS, and to offer guidance for the clinical application of injection therapy. Trial registration Chinese Clinical Trial Registry ChiCTR2400094746. Registered on 26 December 2024, https://www.chictr.org.cn/showproj.html?proj=252770 Carpal Tunnel Syndrome Platelet-Rich Plasma Different doses Randomized Controlled Trail Protocol Figures Figure 1 Introduction Carpal tunnel syndrome (CTS) is a condition in which the compression of median nerve in the carpal tunnel leads to sensory and motor changes, such as paresthesia and dyskinesia, in the area served by the median nerve. It is the most common disorder among peripheral entrapment neuropathies. The prevalence of CTS ranges from 0.2–4% overall, with higher rates observed in females compared to males (10%: 5.8%)[ 1 ] . The treatment of CTS includes both conservative and operative approaches. The main conservative treatment options consist of wrist splints, local steroid injections, oral medications, etc. However, the effectiveness of these treatments is not always satisfactory[ 2 ]. Previous studies have shown that approximately half of the CTS patients who undergo conservative treatments eventually require surgery[ 3 ]. Although surgery is effective, it can result in postoperative trauma, and there is still a risk of secondary entrapment. Therefore, it is necessary to search for a new treatment for CTS. Platelet-rich plasma (PRP) is a concentrated form of platelets obtained by spinning autologous blood, which contains abundant platelets and a high concentration of trophic factors[ 4 – 6 ]. PRP not only has excellent anti-inflammatory and tissue repair abilities but also promotes the regeneration of peripheral neurons[ 5 , 7 – 8 ]. It has been widely used in treating refractory wounds, lateral epicondylitis of the humerus, plantar fasciitis, etc.[ 9 – 11 ]. Currently, clinical studies have demonstrated the efficacy of ultrasound-guided injection of PRP for treating CTS and effectively alleviating symptoms in patients with moderate conditions[ 10 , 12 , 13 ]. Several published studies have demonstrated that ultrasound image-guided carpal tunnel injection of 3mL PRP can effectively alleviate the symptoms of moderate CTS. Some studies have found that 4–5 mL of PRP can also be an optional dose to improve symptoms. However, there is still a lack of recognized standards and norms for the dosage of PRP injections in the carpal tunnel. Therefore, we aim to further explore the optimal dose of PRP injection for CTS with the assistance of ultrasound imaging technology. This study aims to provide a new clinical reference for the standard injection treatment of moderate CTS. In this study, eligible participants are randomly divided into two groups: a 3mL PRP group and a 5mL PRP group. We hypothesis that a 5mL PRP injection may yield more effective amelioration in symptoms compared to a 3mL PRP injection among individuals afflicted with moderate CTS. Methods and analysis Study design The study on PRP injection for CTS is a prospective, double-blind, randomized, controlled clinical trial which will be conducted by the Third Affiliated Hospital of Southern Medical University. The protocol follows the requirements of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline (Fig. 1 ) [ 16 ]. Ethics and dissemination This study design was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Southern Medical University (2024-ER-059). The trial is registered at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn ). The final results will be published in peer-reviewed journals and conferences. Recruitment and informed consent Participants recruitment starts from September 2024 in patients with CTS at the outpatient department of Rehabilitation Medicine. Patients will be assigned into two trial groups at a ratio of 1:1 with a complete randomization method after a selection by screening inclusion and exclusion criteria. The investigator should inform the participants, before the start of the study, about all relevant aspects of the clinical study using language that is easy to understand. Additionally, the participants should be informed of their right to withdraw from the study at any time. The study could only begin after the participants voluntarily signed the informed consent form. Eligibility criteria Inclusion criteria Aged 20–80 years; Diagnosed as moderate CTS based on the results of electromyography (prolonged latency of sensory and motor nerve potentials at the end of the median nerve), and with symptoms related to carpal tunnel over 1 month; Numbness of at least 40mm on a 100mm VAS; Normal platelet count and coagulation function; No history of long-term smoking or alcohol consumption; No language and cognitive disorder; Volunteered to participate in this trial and sign the informed consent. Exclusion criteria Previous or planned wrist surgery within the past 6 months or a previous history of severe wrist trauma; Receiving any injections in the carpal tunnel in the past 4 weeks; Severe skin damage or ulcers around the wrist; Systemic corticosteroids used in the past 2 weeks and non-steroidal anti-inflammatory drugs in the past 1 week; Previous anticoagulant or antiplatelet drugs during the past month; Patients with diabetes, gout, metabolic disorders, digestive tract issues, tumors, blood disorders, or other basic diseases; Patients with cervical spondylosis, brachial plexus disease, lateral epicondylitis, thoracic outlet syndrome, or other conditions; Pregnancy or current breast feeding; Patients with hemoglobin < 10 g/L, platelet count < 150 x 10 9 /L; History of infectious diseases, such as positive tests for hepatitis B, HIV, and syphilis prior to the operation; Patients recent febrile illness; Patients with non-invasive treatment contraindications or have previously participated in similar experiments with carpal tunnel PRP injection. Withdrawal If participants experience severe adverse events, such as nausea, vomiting, and palpitations, that prevent them from continuing with the trial according to the evaluation, or if they voluntarily withdraw from the trial during the intervention, they will be considered to have automatically withdrawn from the trial. If a participant withdraws or is removed from the study, the reason and date of discontinuation will be recorded. Sample size The calculation is performed using G*power V.3.1.9.2. This project took patients with moderate carpal tunnel syndrome as research objects. Referring to previous studies on PRP in the treatment of carpal tunnel syndrome[ 10 , 12 – 15 ], the effect size is 0.51. Using an F-test, with a two-sided significance level of 0.05 and a power of 0.95, the required sample size is determined to be 54. Considering a 10% dropout rate, the total sample size will be 60 participants. Randomization This study is a prospective, double-blind, randomized controlled experiment. The study site is the department of Rehabilitation Medicine of the Third Affiliated Hospital of Southern Medical University. After consent and completion of the baseline assessment, the participants will be randomly assigned to two groups at a ratio of 1:1 by complete randomization. The random numbers will be generated by using SPSS software (V.26.0) and each participant will be assigned a randomized number and allocated to different group. Blinding This study adopts a double-blind design where both participants and researchers (including outcome measurers and data analysis) are unaware of the grouping. The administering physician, however, is not blinded due to varying dosages of the experimental drug. The PRP preparation occurs out of sight of participants and investigators, with syringes shielded by opaque material to maintain blindness. During administration, participants are seated with relaxed wrists; if needed, a mask prevents them from observing the injection. Adherence to Consolidated Standards of Reporting Trials (CONSORT) guidelines is ensured. Each sealed envelope contains blinded assignment details. Upon completing case collection, the database is locked. Initial unblinding reveals participants numbers corresponding to Group 1 or Group 2 without disclosing specific group identities. Subsequent unblinding follows data analysis to disclose experimental and control group allocations. In cases of urgent unblinding for serious adverse events, letters with instructions matching participants numbers are opened to determine drug assignments. Once opened, cases are documented in the Emergency Unblinding Report Form, and the sponsor is promptly notified. Interventions Each group will receive two injections and undergo four follow-up sessions over a 6-month period. All participants will receive health education and ultrasound-guided PRP injections for carpal tunnel syndrome on day 1 and day 14 after being assigned to their respective groups. The key distinction between groups lies in the dosage of PRP administered into the carpal tunnel: the experimental group will receive a 5 mL PRP injection, whereas the control group will receive 3 mL. Detailed injection procedures with ultrasound guidance are as follows: Participants are seated next to the ultrasound bed, positioning their forearms horizontally on the bed with relaxed wrists and slight flexion of the metacarpophalangeal and proximal interphalangeal joints. The ultrasound probe is placed transversely at the carpal tunnel to visualize the maximum cross-section of the median nerve. Following skin preparation and draping, the operator stabilizes the probe with one hand while holding the syringe with the other. The needle is inserted into the carpal tunnel, guided in real-time by ultrasound imaging, entering from the ulnar side. The syringe is inspected for any abnormalities before proceeding to inject the drug solution. Injection is performed at two locations: one in the upper part and one in the lower part of the median nerve. Health education: Participants should minimize repetitive hand and wrist movements and use wrist rests as needed, especially reducing activities that excessively strain the wrists, such as prolonged bicycling. Individuals with jobs involving frequent wrist movements should ensure adequate rest periods for their wrists. It is recommended to take brief breaks every half hour to relax the wrists. Outcome measures This study aims to compare baseline indices with those at the 6-month follow-up. A schedule detailing the time points for collecting each outcome indicator is provided in Table 1 . Participants will complete questionnaires and return them to the department via mail or email. A dedicated nurse will handle follow-up calls or messages concerning the use of other medications and any adverse reactions during the treatment process. Table 1 Schedule of enrolment, interventions, and assessments STUDY PERIOD Enrolment Intervention Follow-up Timepoint Screening Baseline 2 weeks 1 month 3 months 6 months ENROLMENT: Eligibility screen × Informed consent × Allocation × INTERVENTIONS: 3ml group × × 5ml group × × ASSESSMENTS: Primary outcome VAS of numbness × × × × Secondary outcomes BCTQ-SSS × × × × BCTQ-FSS × × × × SNCV × × × × DMS × × × × CSA × × × × MNBF × × × × MNSR × × × × Adverse reactions × × × × Exploratory outcomes Concentration of PRP × Concentration of active factors in PRP × Cellular composition proportions × Other outcomes Basic information × Clinical evaluation × Use of medications or supplements × × × × Adverse events × × × × Parameters of coagulation function × Parameters of blood analysis × Blank, no assessment; VAS, Visual Analogue Scale; BCTQ-SSS, Boston Carpal Tunnel Syndrome Questionnaire-Symptom Severity Scale; BCTQ-FSS, Boston Carpal Tunnel Syndrome Questionnaire-Functional Status Scale; SNCV, Sensory nerve conduction velocity; DML, Distal motor latency; CSA, Cross-sectional area; MNBF, Blood flow of median nerve; MNSR, Swollen rate of median nerve; ×, assessment. Primary outcome The primary outcome measure is the Visual Analogue Scale (VAS) assessing wrist numbness over the past 7 days. The VAS scale ranges from 0 to 100 mm, with each millimeter representing one point on the scale. Secondary outcome Secondary outcomes include the assessment of patients’ symptoms and activities of daily living using questionnaires. Additionally, ultrasound imaging and electromyography are employed to collect pertinent data on the median nerve of participants. Specifically, the study utilizes the following measures: The BCTQ-SSS and BCTQ-FSS are self-assessment scales used to evaluate symptoms in patients with carpal tunnel syndrome. The BCTQ-SSS comprises 11 items, while the BCTQ-FSS includes 8 items. Each item is scored on a 5-point Likert scale, with higher scores indicating more severe CTS symptoms. Electromyography (EMG) examinations are conducted to record statistics of the median nerve, including sensory nerve conduction velocity (SNCV) and distal motor latency (DML). All examinations are performed using an electromyogram evoked potential meter at a room temperature of 25°C, with the hand temperature maintained at or above 32°C. The nerve is stimulated at both the wrist and elbow levels, and data are recorded from the median nerve at the wrist area, including SNCV and DML metrics. The data from the first finger represent motor conduction, the middle finger is used for sensory conduction, and the fifth finger is utilized for ulnar nerve conduction. During the examination and treatment process, a doctor uses a color Doppler ultrasound instrument, converting it to the musculoskeletal model before beginning. The participants sit on a seat next to the ultrasound bed with their forearms placed horizontally on the examination bed, wrists relaxed, and the joints between their palms and proximal fingers slightly flexed. The ultrasound probe is positioned perpendicular to the long axis of the forearm to measure the cross-sectional area (CSA) of the median nerve, the distribution of blood flow in the median nerve, and the swelling rate (the ratio of the most prominent swelling to the thinnest part), among other indicators. Adverse reactions: We will record any adverse reactions to medication over the past 4 weeks at each follow-up visit. Other Outcomes We have set three exploratory outcomes focusing on the concentration of PRP, the concentration of active factors (PDGF and VEGF) in PRP, and cellular composition proportions in PRP. During PRP preparation, 1ml of the sample will be reserved for subsequent analysis. The concentration of PDGF and VEGF in PRP will be detected by the laboratory technicians of Zhuhai Longtai Biotechnology Co., LTD. Co-intervention assessments No other medication or surgical treatment will be administered to the participants during the trial. Physical therapy should not be provided to the participants one week before the visit. Statistical plan The baseline characteristics of the experimental group and the control group will be presented in different forms based on the type of data. The mean and standard deviation will be used to describe normally distributed data. The median and interquartile range will be used to present non-normally distributed data. Proportions will be used to represent dichotomous variables. The intention-to-treat analysis will serve as the primary analytical method in this trial, with per-protocol analysis as a secondary method. Participants who complete four follow-ups will be included in the per-protocol analysis. Multiple imputation based on chained equations will be used to handle missing data resulting from loss to follow-up and nonresponse. Baseline outcome measures including age, sex, body mass index, and other outcome measures that are not missing at follow-up time points will be used for imputation of missing outcome measures for the two groups. A linear mixed-effects model will be used to analyze the effects of treatment on symptoms, changes in the median nerve, and quality of life in patients with carpal tunnel syndrome. The fixed effects of the model will include the interaction between baseline covariates (age, sex, body mass index, and baseline values of efficacy measures) and follow-up time, as well as their respective main effects. The interaction between treatment and follow-up time, along with their respective main effects, will be analyzed. The trial site and subject will be included as random intercepts, and follow-up time will be included as random slopes. The changes and differences in efficacy measures between the two groups during follow-up will be calculated by applying a linear combination of the estimated coefficients. Safety assessments Adverse events will be recorded at each visit, and participants will be asked to report any adverse events to the study staff. If a participant experiences an adverse event, the investigator will determine the relationship between the event and the medication. For serious adverse events, study physicians are instructed to take any necessary immediate steps to ensure the safety of the study participants and report these events to both the sponsor and the hospital’s ethics committee within 24 hours. Participants experiencing adverse events will be monitored until recovery or remission of the adverse events using methods such as outpatient examinations, home visits, telephone calls, and WeChat. The occurrence time, symptoms, duration, treatment measures, outcomes, and adverse reactions of adverse events will be recorded in the adverse event record book. Quality assurance Before the trial commences, standard operating procedures for clinical trials are established to standardize the methods of operation, criteria for judgment, and the documentation form of the relevant data throughout the trial. This ensures that researchers adhere strictly to the protocol when conducting relevant operations. The principal investigator provides training on the clinical trial protocol, standard operating procedures, and special precautions to all participating healthcare personnel. Experienced injection operators and nursing teams are selected to ensure a smooth injection treatment process. Researchers should actively take measures to achieve a dropout rate below 20%. The protocol will not be altered during the whole study period. Data management A database platform is utilized to ensure quality control in data collection, data entry, and the protection of participants’ confidentiality. Participants who cannot enter data directly into the database system will be given paper case-report forms to complete. Study personnel will then enter the data into the database system and periodically review recent entries to prevent errors. In addition to regularly entering patient data into the database, we will routinely back up the patients’ ultrasound images and EMG data in the local cloud. The relevant documents should be accurately and carefully recorded according to the requirements, and the contents should not be easily altered once they have been filled in. If corrections are necessary due to errors, the original records should not be modified but should be amended with additional narratives, which must be signed and dated by the responsible investigator. Regular site monitoring visits, conducted by monitors dispatched by the principal investigators, ensure strict adherence to all protocol elements. Monitors review the original data to ensure that the content of CRFs is true and reliable. The sponsor may appoint monitors to conduct systematic reviews of clinical trial-related activities and documents to evaluate whether the trial is being conducted in accordance with the protocol, standard operating procedures, and relevant legal and regulatory requirements. They also assess whether trial data is being recorded in a timely, true, accurate, and complete manner. The principal investigator will be responsible for ensuring quality control of this clinical trial. During the study, the trial leader will conduct spot checks to review the progress of the trial. The researchers of this study have access to the trial’s final database. The government administration or members of the ethics review committee may access the personal data of participants stored at the study institution when required. Any private personal information about participants will not be disclosed when the results of this study are published. Discussion Carpal tunnel injections can significantly reduce the symptoms of patients with carpal tunnel syndrome (CTS) and improve their quality of life. PRP injection in the carpal tunnel is one of the new treatment methods in recent years. Existing clinical studies recommend a dose range of 1-5ml for carpal tunnel injection, but the effectiveness of different doses in improving symptoms remains a topic of debate. Some studies indicate that PRP injections in doses of 1-3ml can notably enhance the functional symptoms of CTS patients[ 17 ], while other studies validate the efficacy of doses ranging from 4-5ml. Currently, there is a shortage of comparative studies on various dosage levels. Therefore, more high-quality clinical studies are needed to determine the optimal PRP dose for patients with moderate CTS. One innovation of this study is the use of various PRP dose groups. The choice of injection dose may relate to the degree of symptom improvement in patients with moderate CTS. In this study, each PRP preparation for participants is conducted strictly according to the instructions of the PRP preparation kit used. Considering the preparation requirements and tube specifications in the kit, combined with the biological effects of PRP, previous studies, and our clinical experience, two dose groups of 3ml and 5ml are selected for study and efficacy comparison. The comprehensive evaluation method is also a highlight of this study. The VAS score evaluates the severity of numbness, while the BCTQ score assesses clinical symptoms and hand function of CTS patients. Nerve electromyography measures the latency of the median nerve, and ultrasound evaluates the cross-sectional area and blood supply of the median nerve. These data comprehensively and accurately reflect patient symptoms and the extent of median nerve damage. In order to investigate whether various PRP parameters impact the effectiveness of treating CTS patients, we also intend to analyze the PRP concentration, active factor concentration, and cell content in the PRP of patients. We expect that the results of this part will provide a theoretical basis for the effectiveness of different doses of PRP in the treatment of CTS. Our study also has some limitations. Due to the high economic cost of PRP treatment, participants are all from a single center, so the sample representation needs to be expanded. Additionally, considering economic constraints and patient adherence, the maximum follow-up period in the current study is only 6 months after injection. In conclusion, the results of this study can provide a basis for determining the optimal therapeutic dose of PRP for moderate CTS and fill the gap in studies related to PRP injection in the treatment of moderate CTS. Additionally, we hope that there will be opportunities to conduct relevant multi-center studies in the future to enhance the objectivity of the research results and to collect longer-term follow-up information about CTS patients. Trial status The version of this protocol is 4.0 ( Date 23 March 2024 ). The recruitment began on 30 September 2024 and the expected completed date is 30 November 2026. Abbreviations CTS Carpal tunnel syndrome PRP Platelet-rich plasma VAS Visual Analogue Scale BCTQ-SSS Boston Carpal Tunnel Syndrome Questionnaire-Symptom Severity Scale BCTQ-FSS Boston Carpal Tunnel Syndrome Questionnaire-Functional Status Scale SNCV Sensory nerve conduction velocity DML Distal motor latency CSA Cross-sectional area MNBF Blood flow of median nerve MNSR Swollen rate of median nerve Declarations Authors’ contributions LJ is the project manager of the study and is responsible for the study design. WH and HF played a major role in the study design and will be responsible for participants’ enrolment. YL, YL and ZW have made equal contributions to this protocol particularly in terms of the drafting the manuscript. ZL oversees the coordination of the trial and will be in charge of administering injections. MG and GX contributed to the calculation of the sample size and future statistical analysis. Additionally, LY and LK will be accountable for enrolling participants and take charge of injections and platelet-rich plasma (PRP) preparation, respectively. Acknowledgements We appreciate Zhuhai Longtai Biotechnology Co., LTD. (http://www.longtimebio.cn) for providing the PRP preparation kit used in this research. A special acknowledgement to Professor Li Ling, the statistician who gave selfless, earnest and valuable guidance from study design to statistics method to this study. We also appreciate LiShuo Shi who provided helpful suggestions on statistical methods, and research nurses Lingling Zeng, Chuanye Ju, Lihua Tang and Wan Zhang. Funding This work is supported by Guangzhou Municipal Science and Technology Project, grant number 202206010195. Availability of data and materials Data will be available from the corresponding author upon reasonable request. Consent for publication Not applicable. Competing interests None declared. Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Once the trial has been published, participants will be informed of the results by telephone. References Chiu YH, Chang KV, Chen IJ, Wu WT, Özçakar L. Utility of sonoelastography for the evaluation of rotator cuff tendon and pertinent disorders: a systematic review and meta-analysis. Eur Radiol. 2020;30(12):6663–72. Ostergaard PJ, Meyer MA, Earp BE. Non-operative Treatment of Carpal Tunnel Syndrome. Curr Rev Musculoskelet Med. 2020;13(2):141-47. Burton CL, Chesterton LS, Chen Y, van der Windt DA. Clinical Course and Prognostic Factors in Conservatively Managed Carpal Tunnel Syndrome: A Systematic Review. Arch Phys Med Rehabil. 2016;97(5):836-52.e1. Razmara M, Hjemdahl P, Ostenson CG, Li N. Platelet hyperprocoagulant activity in Type 2 diabetes mellitus: attenuation by glycoprotein IIb/IIIa inhibition. 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Comparison of perineural platelet‐rich plasma and dextrose injections for moderate carpal tunnel syndrome: A prospective randomized, single‐blind, head‐to‐head comparative trial. J Tissue Eng Regen Med. 2019;13(11):2009–17. Raeissadat SA, Karimzadeh A, Hashemi M, Bagherzadeh L. Safety and efficacy of platelet-rich plasma in treatment of carpal tunnel syndrome; a randomized controlled trial. BMC Musculoskelet Disord. 2018;19(1):49. Hofer M, Ranstam J, Atroshi I. Extended Follow-up of Local Steroid Injection for Carpal Tunnel Syndrome. JAMA Netw Open. 2021;4 (10): e2130753. Chan AW, Tetzlaff JM, Gøtzsche PC, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586. Venkataraman S, Benny R, AsemRangita Chanu, et al. A Randomized Controlled Trial to Compare the Effect of Ultrasound-Guided, Single-Dose Platelet-Rich Plasma and Corticosteroid Injection in Patients with Carpal Tunnel Syndrome. The Journal of the international society of physical and rehabilitation medicine. 2022;5:90–6. Supplementary Files ExplanationofFundingSupport.docx SPIRITchecklist.docx Cite Share Download PDF Status: Published Journal Publication published 25 Feb, 2026 Read the published version in Trials → Version 1 posted Reviewers agreed at journal 29 Oct, 2025 Reviewers invited by journal 07 Jul, 2025 Editor assigned by journal 17 Jun, 2025 First submitted to journal 14 Jun, 2025 Editorial decision: Revise before peer review 12 Jun, 2025 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. 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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-6534984","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":481653551,"identity":"9b5288bc-9f6b-439c-8014-b57cbcb870f4","order_by":0,"name":"Yuxi Li","email":"data:image/png;base64,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","orcid":"https://orcid.org/0009-0005-1112-9656","institution":"Sun Yat-sen University Sixth Affiliated Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yuxi","middleName":"","lastName":"Li","suffix":""},{"id":481653552,"identity":"f199c481-3563-4246-8bfd-047d89dff164","order_by":1,"name":"Ying Lu","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-Sen 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mengxia","middleName":"","lastName":"Guo","suffix":""},{"id":481653556,"identity":"ed27b2c2-6645-42e8-a2e6-fb14121ccef8","order_by":5,"name":"Guobin Xu","email":"","orcid":"","institution":"The Third Affiliated Hospital of Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Guobin","middleName":"","lastName":"Xu","suffix":""},{"id":481653557,"identity":"905bdea4-c418-426b-9041-c2195389e22c","order_by":6,"name":"Lianjun Yin","email":"","orcid":"","institution":"The Third Affiliated Hospital of Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lianjun","middleName":"","lastName":"Yin","suffix":""},{"id":481653558,"identity":"a5f57da3-5f85-474d-a8e9-a88f8966afb0","order_by":7,"name":"Li Kuang","email":"","orcid":"","institution":"The Third Affiliated Hospital of Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Kuang","suffix":""},{"id":481653559,"identity":"54aaa49a-c500-41c0-bbc1-52fdaa6a912b","order_by":8,"name":"Huiting Feng","email":"","orcid":"","institution":"Sun Yat-sen University Sixth Affiliated Hospital","correspondingAuthor":false,"prefix":"","firstName":"Huiting","middleName":"","lastName":"Feng","suffix":""},{"id":481653560,"identity":"5ca2da45-2357-4d9e-98f6-dc902d83bc0e","order_by":9,"name":"Wenjie Hu","email":"","orcid":"","institution":"The Third Affiliated Hospital of Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wenjie","middleName":"","lastName":"Hu","suffix":""},{"id":481653561,"identity":"34c27362-5f89-4f7b-9094-52010bd48168","order_by":10,"name":"Li Jiang","email":"","orcid":"https://orcid.org/0000-0002-5759-9689","institution":"The Third Affiliated Hospital of Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Jiang","suffix":""}],"badges":[],"createdAt":"2025-04-26 12:27:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6534984/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6534984/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13063-026-09538-1","type":"published","date":"2026-02-25T15:58:34+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86318482,"identity":"6b04a116-5377-4e40-a26e-e11cbb33fb2e","added_by":"auto","created_at":"2025-07-09 09:22:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":147918,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart illustrating the process of the study. CTS, carpal tunnel syndrome; PRP, platelet-rich plasma; VAS, Visual Analogue Scale; BCTQ-SSS, Boston Carpal Tunnel Syndrome Questionnaire-Symptom Severity Scale; BCTQ-FSS, Boston Carpal Tunnel Syndrome Questionnaire-Functional Status Scale; SNCV, Sensory nerve conduction velocity; DML, Distal motor latency; CSA, Cross-sectional area; MNBF, Blood flow of median nerve; MNSR, Swollen rate of median nerve.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6534984/v1/6f66175514ae5d248356a681.png"},{"id":103765576,"identity":"9ce89cb3-4adf-4453-946c-dc90be89649b","added_by":"auto","created_at":"2026-03-02 16:04:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":918126,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6534984/v1/c3ad008e-6828-4e0b-b20c-1dc912aa564c.pdf"},{"id":86318492,"identity":"61bfea34-9423-4785-85c7-977cfe39f400","added_by":"auto","created_at":"2025-07-09 09:22:05","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":16836,"visible":true,"origin":"","legend":"","description":"","filename":"ExplanationofFundingSupport.docx","url":"https://assets-eu.researchsquare.com/files/rs-6534984/v1/5699ecb8ac2c727a3329704c.docx"},{"id":86318490,"identity":"19ad86d3-47a0-4cb0-b86d-7f316e6cb2df","added_by":"auto","created_at":"2025-07-09 09:22:04","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":40643,"visible":true,"origin":"","legend":"","description":"","filename":"SPIRITchecklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-6534984/v1/2209fe1e010c1c27be99bd8a.docx"}],"financialInterests":"","formattedTitle":"Efficacy of different doses of Platelet-Rich Plasma for Moderate Carpal Tunnel Syndrome:Study Protocol for a Prospective, Randomized, Controlled trail","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCarpal tunnel syndrome (CTS) is a condition in which the compression of median nerve in the carpal tunnel leads to sensory and motor changes, such as paresthesia and dyskinesia, in the area served by the median nerve. It is the most common disorder among peripheral entrapment neuropathies. The prevalence of CTS ranges from 0.2\u0026ndash;4% overall, with higher rates observed in females compared to males (10%: 5.8%)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] .\u003c/p\u003e\u003cp\u003eThe treatment of CTS includes both conservative and operative approaches. The main conservative treatment options consist of wrist splints, local steroid injections, oral medications, etc. However, the effectiveness of these treatments is not always satisfactory[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Previous studies have shown that approximately half of the CTS patients who undergo conservative treatments eventually require surgery[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Although surgery is effective, it can result in postoperative trauma, and there is still a risk of secondary entrapment. Therefore, it is necessary to search for a new treatment for CTS.\u003c/p\u003e\u003cp\u003ePlatelet-rich plasma (PRP) is a concentrated form of platelets obtained by spinning autologous blood, which contains abundant platelets and a high concentration of trophic factors[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. PRP not only has excellent anti-inflammatory and tissue repair abilities but also promotes the regeneration of peripheral neurons[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It has been widely used in treating refractory wounds, lateral epicondylitis of the humerus, plantar fasciitis, etc.[\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Currently, clinical studies have demonstrated the efficacy of ultrasound-guided injection of PRP for treating CTS and effectively alleviating symptoms in patients with moderate conditions[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSeveral published studies have demonstrated that ultrasound image-guided carpal tunnel injection of 3mL PRP can effectively alleviate the symptoms of moderate CTS. Some studies have found that 4\u0026ndash;5 mL of PRP can also be an optional dose to improve symptoms. However, there is still a lack of recognized standards and norms for the dosage of PRP injections in the carpal tunnel. Therefore, we aim to further explore the optimal dose of PRP injection for CTS with the assistance of ultrasound imaging technology. This study aims to provide a new clinical reference for the standard injection treatment of moderate CTS.\u003c/p\u003e\u003cp\u003eIn this study, eligible participants are randomly divided into two groups: a 3mL PRP group and a 5mL PRP group. We hypothesis that a 5mL PRP injection may yield more effective amelioration in symptoms compared to a 3mL PRP injection among individuals afflicted with moderate CTS.\u003c/p\u003e"},{"header":"Methods and analysis","content":"\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003eThe study on PRP injection for CTS is a prospective, double-blind, randomized, controlled clinical trial which will be conducted by the Third Affiliated Hospital of Southern Medical University. The protocol follows the requirements of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eEthics and dissemination\u003c/h2\u003e\u003cp\u003e This study design was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Southern Medical University (2024-ER-059). The trial is registered at the Chinese Clinical Trial Registry (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.chictr.org.cn\u003c/span\u003e\u003cspan address=\"http://www.chictr.org.cn\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). The final results will be published in peer-reviewed journals and conferences.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eRecruitment and informed consent\u003c/h3\u003e\n\u003cp\u003eParticipants recruitment starts from September 2024 in patients with CTS at the outpatient department of Rehabilitation Medicine. Patients will be assigned into two trial groups at a ratio of 1:1 with a complete randomization method after a selection by screening inclusion and exclusion criteria. The investigator should inform the participants, before the start of the study, about all relevant aspects of the clinical study using language that is easy to understand. Additionally, the participants should be informed of their right to withdraw from the study at any time. The study could only begin after the participants voluntarily signed the informed consent form.\u003c/p\u003e\n\u003ch3\u003eEligibility criteria\u003c/h3\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eInclusion criteria\u003c/h2\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eAged 20\u0026ndash;80 years;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eDiagnosed as moderate CTS based on the results of electromyography (prolonged latency of sensory and motor nerve potentials at the end of the median nerve), and with symptoms related to carpal tunnel over 1 month;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eNumbness of at least 40mm on a 100mm VAS;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eNormal platelet count and coagulation function;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eNo history of long-term smoking or alcohol consumption;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eNo language and cognitive disorder;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eVolunteered to participate in this trial and sign the informed consent.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eExclusion criteria\u003c/h3\u003e\n\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003ePrevious or planned wrist surgery within the past 6 months or a previous history of severe wrist trauma;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eReceiving any injections in the carpal tunnel in the past 4 weeks;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eSevere skin damage or ulcers around the wrist;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eSystemic corticosteroids used in the past 2 weeks and non-steroidal anti-inflammatory drugs in the past 1 week;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePrevious anticoagulant or antiplatelet drugs during the past month;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePatients with diabetes, gout, metabolic disorders, digestive tract issues, tumors, blood disorders, or other basic diseases;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePatients with cervical spondylosis, brachial plexus disease, lateral epicondylitis, thoracic outlet syndrome, or other conditions;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePregnancy or current breast feeding;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePatients with hemoglobin\u0026thinsp;\u0026lt;\u0026thinsp;10 g/L, platelet count\u0026thinsp;\u0026lt;\u0026thinsp;150 x 10\u003csup\u003e9\u003c/sup\u003e/L;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eHistory of infectious diseases, such as positive tests for hepatitis B, HIV, and syphilis prior to the operation;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePatients recent febrile illness;\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePatients with non-invasive treatment contraindications or have previously participated in similar experiments with carpal tunnel PRP injection.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eWithdrawal\u003c/h2\u003e\u003cp\u003eIf participants experience severe adverse events, such as nausea, vomiting, and palpitations, that prevent them from continuing with the trial according to the evaluation, or if they voluntarily withdraw from the trial during the intervention, they will be considered to have automatically withdrawn from the trial. If a participant withdraws or is removed from the study, the reason and date of discontinuation will be recorded.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSample size\u003c/h3\u003e\n\u003cp\u003eThe calculation is performed using G*power V.3.1.9.2. This project took patients with moderate carpal tunnel syndrome as research objects. Referring to previous studies on PRP in the treatment of carpal tunnel syndrome[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], the effect size is 0.51. Using an F-test, with a two-sided significance level of 0.05 and a power of 0.95, the required sample size is determined to be 54. Considering a 10% dropout rate, the total sample size will be 60 participants.\u003c/p\u003e\n\u003ch3\u003eRandomization\u003c/h3\u003e\n\u003cp\u003eThis study is a prospective, double-blind, randomized controlled experiment. The study site is the department of Rehabilitation Medicine of the Third Affiliated Hospital of Southern Medical University. After consent and completion of the baseline assessment, the participants will be randomly assigned to two groups at a ratio of 1:1 by complete randomization. The random numbers will be generated by using SPSS software (V.26.0) and each participant will be assigned a randomized number and allocated to different group.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eBlinding\u003c/h2\u003e\u003cp\u003eThis study adopts a double-blind design where both participants and researchers (including outcome measurers and data analysis) are unaware of the grouping. The administering physician, however, is not blinded due to varying dosages of the experimental drug.\u003c/p\u003e\u003cp\u003eThe PRP preparation occurs out of sight of participants and investigators, with syringes shielded by opaque material to maintain blindness. During administration, participants are seated with relaxed wrists; if needed, a mask prevents them from observing the injection. Adherence to Consolidated Standards of Reporting Trials (CONSORT) guidelines is ensured. Each sealed envelope contains blinded assignment details. Upon completing case collection, the database is locked. Initial unblinding reveals participants numbers corresponding to Group 1 or Group 2 without disclosing specific group identities. Subsequent unblinding follows data analysis to disclose experimental and control group allocations.\u003c/p\u003e\u003cp\u003eIn cases of urgent unblinding for serious adverse events, letters with instructions matching participants numbers are opened to determine drug assignments. Once opened, cases are documented in the Emergency Unblinding Report Form, and the sponsor is promptly notified.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eInterventions\u003c/h2\u003e\u003cp\u003eEach group will receive two injections and undergo four follow-up sessions over a 6-month period. All participants will receive health education and ultrasound-guided PRP injections for carpal tunnel syndrome on day 1 and day 14 after being assigned to their respective groups. The key distinction between groups lies in the dosage of PRP administered into the carpal tunnel: the experimental group will receive a 5 mL PRP injection, whereas the control group will receive 3 mL.\u003c/p\u003e\u003cp\u003eDetailed injection procedures with ultrasound guidance are as follows:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eParticipants are seated next to the ultrasound bed, positioning their forearms horizontally on the bed with relaxed wrists and slight flexion of the metacarpophalangeal and proximal interphalangeal joints.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe ultrasound probe is placed transversely at the carpal tunnel to visualize the maximum cross-section of the median nerve.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eFollowing skin preparation and draping, the operator stabilizes the probe with one hand while holding the syringe with the other. The needle is inserted into the carpal tunnel, guided in real-time by ultrasound imaging, entering from the ulnar side.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe syringe is inspected for any abnormalities before proceeding to inject the drug solution.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eInjection is performed at two locations: one in the upper part and one in the lower part of the median nerve.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003eHealth education:\u003c/p\u003e\u003cp\u003eParticipants should minimize repetitive hand and wrist movements and use wrist rests as needed, especially reducing activities that excessively strain the wrists, such as prolonged bicycling. Individuals with jobs involving frequent wrist movements should ensure adequate rest periods for their wrists. It is recommended to take brief breaks every half hour to relax the wrists.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eOutcome measures\u003c/h2\u003e\u003cp\u003eThis study aims to compare baseline indices with those at the 6-month follow-up. A schedule detailing the time points for collecting each outcome indicator is provided in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Participants will complete questionnaires and return them to the department via mail or email. A dedicated nurse will handle follow-up calls or messages concerning the use of other medications and any adverse reactions during the treatment process.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSchedule of enrolment, interventions, and assessments\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"6\" nameend=\"c7\" namest=\"c2\"\u003e\u003cp\u003eSTUDY PERIOD\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eEnrolment\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e\u003cb\u003eIntervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e\u003cb\u003eFollow-up\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTimepoint\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eScreening\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 month\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003eENROLMENT:\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEligibility screen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInformed consent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAllocation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003eINTERVENTIONS:\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3ml group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5ml group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003eASSESSMENTS:\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003ePrimary outcome\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVAS of numbness\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003eSecondary outcomes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBCTQ-SSS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBCTQ-FSS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSNCV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDMS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMNBF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMNSR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdverse reactions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003eExploratory outcomes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConcentration of PRP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConcentration of active\u003c/p\u003e\u003cp\u003efactors in PRP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCellular composition proportions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003eOther outcomes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBasic information\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClinical evaluation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUse of medications or supplements\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdverse events\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameters of coagulation function\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameters of blood analysis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eBlank, no assessment; VAS, Visual Analogue Scale; BCTQ-SSS, Boston Carpal Tunnel Syndrome Questionnaire-Symptom Severity Scale; BCTQ-FSS, Boston Carpal Tunnel Syndrome Questionnaire-Functional Status Scale; SNCV, Sensory nerve conduction velocity; DML, Distal motor latency; CSA, Cross-sectional area; MNBF, Blood flow of median nerve; MNSR, Swollen rate of median nerve; \u0026times;, assessment.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003ePrimary outcome\u003c/h2\u003e\u003cp\u003eThe primary outcome measure is the Visual Analogue Scale (VAS) assessing wrist numbness over the past 7 days. The VAS scale ranges from 0 to 100 mm, with each millimeter representing one point on the scale.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eSecondary outcome\u003c/h2\u003e\u003cp\u003eSecondary outcomes include the assessment of patients\u0026rsquo; symptoms and activities of daily living using questionnaires. Additionally, ultrasound imaging and electromyography are employed to collect pertinent data on the median nerve of participants. Specifically, the study utilizes the following measures:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe BCTQ-SSS and BCTQ-FSS are self-assessment scales used to evaluate symptoms in patients with carpal tunnel syndrome. The BCTQ-SSS comprises 11 items, while the BCTQ-FSS includes 8 items. Each item is scored on a 5-point Likert scale, with higher scores indicating more severe CTS symptoms.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eElectromyography (EMG) examinations are conducted to record statistics of the median nerve, including sensory nerve conduction velocity (SNCV) and distal motor latency (DML). All examinations are performed using an electromyogram evoked potential meter at a room temperature of 25\u0026deg;C, with the hand temperature maintained at or above 32\u0026deg;C. The nerve is stimulated at both the wrist and elbow levels, and data are recorded from the median nerve at the wrist area, including SNCV and DML metrics. The data from the first finger represent motor conduction, the middle finger is used for sensory conduction, and the fifth finger is utilized for ulnar nerve conduction.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eDuring the examination and treatment process, a doctor uses a color Doppler ultrasound instrument, converting it to the musculoskeletal model before beginning. The participants sit on a seat next to the ultrasound bed with their forearms placed horizontally on the examination bed, wrists relaxed, and the joints between their palms and proximal fingers slightly flexed. The ultrasound probe is positioned perpendicular to the long axis of the forearm to measure the cross-sectional area (CSA) of the median nerve, the distribution of blood flow in the median nerve, and the swelling rate (the ratio of the most prominent swelling to the thinnest part), among other indicators.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eAdverse reactions: We will record any adverse reactions to medication over the past 4 weeks at each follow-up visit.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eOther Outcomes\u003c/h2\u003e\u003cp\u003eWe have set three exploratory outcomes focusing on the concentration of PRP, the concentration of active factors (PDGF and VEGF) in PRP, and cellular composition proportions in PRP. During PRP preparation, 1ml of the sample will be reserved for subsequent analysis. The concentration of PDGF and VEGF in PRP will be detected by the laboratory technicians of Zhuhai Longtai Biotechnology Co., LTD.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003eCo-intervention assessments\u003c/h2\u003e\u003cp\u003eNo other medication or surgical treatment will be administered to the participants during the trial. Physical therapy should not be provided to the participants one week before the visit.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eStatistical plan\u003c/h2\u003e\u003cp\u003eThe baseline characteristics of the experimental group and the control group will be presented in different forms based on the type of data. The mean and standard deviation will be used to describe normally distributed data. The median and interquartile range will be used to present non-normally distributed data. Proportions will be used to represent dichotomous variables.\u003c/p\u003e\u003cp\u003eThe intention-to-treat analysis will serve as the primary analytical method in this trial, with per-protocol analysis as a secondary method. Participants who complete four follow-ups will be included in the per-protocol analysis. Multiple imputation based on chained equations will be used to handle missing data resulting from loss to follow-up and nonresponse. Baseline outcome measures including age, sex, body mass index, and other outcome measures that are not missing at follow-up time points will be used for imputation of missing outcome measures for the two groups.\u003c/p\u003e\u003cp\u003eA linear mixed-effects model will be used to analyze the effects of treatment on symptoms, changes in the median nerve, and quality of life in patients with carpal tunnel syndrome. The fixed effects of the model will include the interaction between baseline covariates (age, sex, body mass index, and baseline values of efficacy measures) and follow-up time, as well as their respective main effects. The interaction between treatment and follow-up time, along with their respective main effects, will be analyzed. The trial site and subject will be included as random intercepts, and follow-up time will be included as random slopes. The changes and differences in efficacy measures between the two groups during follow-up will be calculated by applying a linear combination of the estimated coefficients.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eSafety assessments\u003c/h2\u003e\u003cp\u003eAdverse events will be recorded at each visit, and participants will be asked to report any adverse events to the study staff. If a participant experiences an adverse event, the investigator will determine the relationship between the event and the medication. For serious adverse events, study physicians are instructed to take any necessary immediate steps to ensure the safety of the study participants and report these events to both the sponsor and the hospital\u0026rsquo;s ethics committee within 24 hours. Participants experiencing adverse events will be monitored until recovery or remission of the adverse events using methods such as outpatient examinations, home visits, telephone calls, and WeChat. The occurrence time, symptoms, duration, treatment measures, outcomes, and adverse reactions of adverse events will be recorded in the adverse event record book.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003eQuality assurance\u003c/h2\u003e\u003cp\u003eBefore the trial commences, standard operating procedures for clinical trials are established to standardize the methods of operation, criteria for judgment, and the documentation form of the relevant data throughout the trial. This ensures that researchers adhere strictly to the protocol when conducting relevant operations. The principal investigator provides training on the clinical trial protocol, standard operating procedures, and special precautions to all participating healthcare personnel. Experienced injection operators and nursing teams are selected to ensure a smooth injection treatment process. Researchers should actively take measures to achieve a dropout rate below 20%. The protocol will not be altered during the whole study period.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\u003ch2\u003eData management\u003c/h2\u003e\u003cp\u003eA database platform is utilized to ensure quality control in data collection, data entry, and the protection of participants\u0026rsquo; confidentiality. Participants who cannot enter data directly into the database system will be given paper case-report forms to complete. Study personnel will then enter the data into the database system and periodically review recent entries to prevent errors. In addition to regularly entering patient data into the database, we will routinely back up the patients\u0026rsquo; ultrasound images and EMG data in the local cloud.\u003c/p\u003e\u003cp\u003eThe relevant documents should be accurately and carefully recorded according to the requirements, and the contents should not be easily altered once they have been filled in. If corrections are necessary due to errors, the original records should not be modified but should be amended with additional narratives, which must be signed and dated by the responsible investigator.\u003c/p\u003e\u003cp\u003eRegular site monitoring visits, conducted by monitors dispatched by the principal investigators, ensure strict adherence to all protocol elements. Monitors review the original data to ensure that the content of CRFs is true and reliable. The sponsor may appoint monitors to conduct systematic reviews of clinical trial-related activities and documents to evaluate whether the trial is being conducted in accordance with the protocol, standard operating procedures, and relevant legal and regulatory requirements. They also assess whether trial data is being recorded in a timely, true, accurate, and complete manner.\u003c/p\u003e\u003cp\u003eThe principal investigator will be responsible for ensuring quality control of this clinical trial. During the study, the trial leader will conduct spot checks to review the progress of the trial.\u003c/p\u003e\u003cp\u003eThe researchers of this study have access to the trial\u0026rsquo;s final database. The government administration or members of the ethics review committee may access the personal data of participants stored at the study institution when required. Any private personal information about participants will not be disclosed when the results of this study are published.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eCarpal tunnel injections can significantly reduce the symptoms of patients with carpal tunnel syndrome (CTS) and improve their quality of life. PRP injection in the carpal tunnel is one of the new treatment methods in recent years. Existing clinical studies recommend a dose range of 1-5ml for carpal tunnel injection, but the effectiveness of different doses in improving symptoms remains a topic of debate. Some studies indicate that PRP injections in doses of 1-3ml can notably enhance the functional symptoms of CTS patients[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], while other studies validate the efficacy of doses ranging from 4-5ml. Currently, there is a shortage of comparative studies on various dosage levels. Therefore, more high-quality clinical studies are needed to determine the optimal PRP dose for patients with moderate CTS.\u003c/p\u003e\u003cp\u003eOne innovation of this study is the use of various PRP dose groups. The choice of injection dose may relate to the degree of symptom improvement in patients with moderate CTS. In this study, each PRP preparation for participants is conducted strictly according to the instructions of the PRP preparation kit used. Considering the preparation requirements and tube specifications in the kit, combined with the biological effects of PRP, previous studies, and our clinical experience, two dose groups of 3ml and 5ml are selected for study and efficacy comparison.\u003c/p\u003e\u003cp\u003eThe comprehensive evaluation method is also a highlight of this study. The VAS score evaluates the severity of numbness, while the BCTQ score assesses clinical symptoms and hand function of CTS patients. Nerve electromyography measures the latency of the median nerve, and ultrasound evaluates the cross-sectional area and blood supply of the median nerve. These data comprehensively and accurately reflect patient symptoms and the extent of median nerve damage.\u003c/p\u003e\u003cp\u003eIn order to investigate whether various PRP parameters impact the effectiveness of treating CTS patients, we also intend to analyze the PRP concentration, active factor concentration, and cell content in the PRP of patients. We expect that the results of this part will provide a theoretical basis for the effectiveness of different doses of PRP in the treatment of CTS.\u003c/p\u003e\u003cp\u003eOur study also has some limitations. Due to the high economic cost of PRP treatment, participants are all from a single center, so the sample representation needs to be expanded. Additionally, considering economic constraints and patient adherence, the maximum follow-up period in the current study is only 6 months after injection.\u003c/p\u003e\u003cp\u003eIn conclusion, the results of this study can provide a basis for determining the optimal therapeutic dose of PRP for moderate CTS and fill the gap in studies related to PRP injection in the treatment of moderate CTS. Additionally, we hope that there will be opportunities to conduct relevant multi-center studies in the future to enhance the objectivity of the research results and to collect longer-term follow-up information about CTS patients.\u003c/p\u003e"},{"header":"Trial status","content":"\u003cp\u003eThe version of this protocol is 4.0 ( Date 23 March 2024 ). The recruitment began on 30 September 2024 and the expected completed date is 30 November 2026.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eCTS\u003c/strong\u003e Carpal tunnel syndrome\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePRP\u003c/strong\u003e Platelet-rich plasma\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVAS\u003c/strong\u003e Visual Analogue Scale\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBCTQ-SSS\u003c/strong\u003e Boston Carpal Tunnel Syndrome Questionnaire-Symptom Severity Scale\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBCTQ-FSS\u003c/strong\u003e Boston Carpal Tunnel Syndrome Questionnaire-Functional Status Scale\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSNCV\u003c/strong\u003e Sensory nerve conduction velocity\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDML\u003c/strong\u003e Distal motor latency\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCSA\u003c/strong\u003e Cross-sectional area\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMNBF\u003c/strong\u003e Blood flow of median nerve\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMNSR\u003c/strong\u003e Swollen rate of median nerve\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLJ is the project manager of the study and is responsible for the study design. WH and HF played a major role in the study design and will be responsible for participants\u0026rsquo; enrolment. YL, YL and ZW have made equal contributions to this protocol particularly in terms of the drafting the manuscript. ZL oversees the coordination of the trial and will be in charge of administering injections. MG and GX contributed to the calculation of the sample size and future statistical analysis. Additionally, LY and LK will be accountable for enrolling participants and take charge of injections and platelet-rich plasma (PRP) preparation, respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciate Zhuhai Longtai Biotechnology Co., LTD. (http://www.longtimebio.cn) for providing the PRP preparation kit used in this research. A special acknowledgement to Professor Li Ling, the statistician who gave selfless, earnest and valuable guidance from study design to statistics method to this study. We also appreciate LiShuo Shi who provided helpful suggestions on statistical methods, and research nurses Lingling Zeng, Chuanye Ju, Lihua Tang and Wan Zhang.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work is supported by Guangzhou Municipal Science and Technology Project, grant number 202206010195.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003eData will be available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e None declared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient and public involvement\u0026nbsp;\u003c/strong\u003ePatients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Once the trial has been published, participants will be informed of the results by telephone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eChiu YH, Chang KV, Chen IJ, Wu WT, \u0026Ouml;z\u0026ccedil;akar L. Utility of sonoelastography for the evaluation of rotator cuff tendon and pertinent disorders: a systematic review and meta-analysis. Eur Radiol. 2020;30(12):6663\u0026ndash;72.\u003c/li\u003e\n\u003cli\u003eOstergaard PJ, Meyer MA, Earp BE. Non-operative Treatment of Carpal Tunnel Syndrome. Curr Rev Musculoskelet Med. 2020;13(2):141-47.\u003c/li\u003e\n\u003cli\u003eBurton CL, Chesterton LS, Chen Y, van der Windt DA. Clinical Course and Prognostic Factors in Conservatively Managed Carpal Tunnel Syndrome: A Systematic Review. Arch Phys Med Rehabil. 2016;97(5):836-52.e1.\u003c/li\u003e\n\u003cli\u003eRazmara M, Hjemdahl P, Ostenson CG, Li N. Platelet hyperprocoagulant activity in Type 2 diabetes mellitus: attenuation by glycoprotein IIb/IIIa inhibition. J Thromb Thrombolysis. 2008;6(12):2186-92. \u003c/li\u003e\n\u003cli\u003eRuzafa N, Pereiro X, Fonollosa A, Araiz J, Acera A, Vecino E. The Effect of Plasma Rich in Growth Factors on Microglial Migration, Macroglial Gliosis and Proliferation, and Neuronal Survival. Front. Pharmacol. 2021;12:606232.\u003c/li\u003e\n\u003cli\u003eZhou S, Qi F, Gong Y, et al. Platelet-Rich Plasma in Female Androgenic Alopecia: A Comprehensive Systematic Review and Meta-Analysis. Front. Pharmacol. 2021;12:642980.\u003c/li\u003e\n\u003cli\u003eZheng C, Zhu Q, Liu X, et al. Effect of platelet-rich plasma (PRP) concentration on proliferation, neurotrophic function and migration of Schwann cells in vitro. J Tissue Eng Regen Med. 2016;10(5):428-36.\u003c/li\u003e\n\u003cli\u003eNegrini F, De Lucia F, Negrini S, et al. Case Report: Rehabilitation After Platelet-Rich Growth Factors\u0026rsquo; Intra-Articular Injections for Knee Osteoarthritis: Two Case Reports of a Home-Based Protocol. Front Pharmacol. 2021;12:718060. \u003c/li\u003e\n\u003cli\u003eChen XT, Fang W, Jones IA, Heckmann ND, Park C, Vangsness CT Jr. The Efficacy of Platelet-Rich Plasma for Improving Pain and Function in Lateral Epicondylitis: A Systematic Review and Meta-analysis with Risk-of-Bias Assessment. Arthroscopy. 2021;37(9):2937-2952.\u003c/li\u003e\n\u003cli\u003eFei X, Lang L, Lingjiao H, Wei C, Zhou X. Platelet-rich plasma has better mid-term clinical results than traditional steroid injection for plantar fasciitis: A systematic review and meta-analysis. Orthop Traumatol Surg Res. 2021;107(6):103007. \u003c/li\u003e\n\u003cli\u003eZhang Y, Xing F, Luo R, Duan X. Platelet-Rich Plasma for Bone Fracture Treatment: A Systematic Review of Current Evidence in Preclinical and Clinical Studies. Front Med (Lausanne). 2021;8:676033.\u003c/li\u003e\n\u003cli\u003eSenna MK, Shaat RM, Ali AAA. Platelet-rich plasma in treatment of patients with idiopathic carpal tunnel syndrome. Clin Rheumatol. 2019;38(12):3643\u0026ndash;54.\u003c/li\u003e\n\u003cli\u003eShen YP, Li TY, Chou YC, et al. Comparison of perineural platelet‐rich plasma and dextrose injections for moderate carpal tunnel syndrome: A prospective randomized, single‐blind, head‐to‐head comparative trial. J Tissue Eng Regen Med. 2019;13(11):2009\u0026ndash;17.\u003c/li\u003e\n\u003cli\u003eRaeissadat SA, Karimzadeh A, Hashemi M, Bagherzadeh L. Safety and efficacy of platelet-rich plasma in treatment of carpal tunnel syndrome; a randomized controlled trial. BMC Musculoskelet Disord. 2018;19(1):49.\u003c/li\u003e\n\u003cli\u003eHofer M, Ranstam J, Atroshi I. Extended Follow-up of Local Steroid Injection for Carpal Tunnel Syndrome. JAMA Netw Open. 2021;4 (10): e2130753. \u003c/li\u003e\n\u003cli\u003eChan AW, Tetzlaff JM, G\u0026oslash;tzsche PC, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586.\u003c/li\u003e\n\u003cli\u003eVenkataraman S, Benny R, AsemRangita Chanu, et al. A Randomized Controlled Trial to Compare the Effect of Ultrasound-Guided, Single-Dose Platelet-Rich Plasma and Corticosteroid Injection in Patients with Carpal Tunnel Syndrome. The Journal of the international society of physical and rehabilitation medicine. 2022;5:90\u0026ndash;6.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Carpal Tunnel Syndrome, Platelet-Rich Plasma, Different doses, Randomized Controlled Trail, Protocol","lastPublishedDoi":"10.21203/rs.3.rs-6534984/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6534984/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eCarpal tunnel syndrome (CTS) is the most prevalent peripheral nerve disorder, with an incidence of approximately 0.4-1% in the general population. Recently, Platelet-rich plasma (PRP) injections attention as an innovative treatment, proving more effective than corticosteroids and dextrose. However, the optimal PRP therapeutic dosage remains unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis double-blind, randomized controlled study will include 60 patients with moderate carpal tunnel syndrome. Participants will be randomly assigned to one of two groups: 3ml PRP or 5ml PRP, which will receive two injections 2 weeks apart. Injections are performed by experienced doctors under ultrasound guidance. Primary outcome measures include changes in the Visual Analogue Scale (VAS) of numbness from baseline to six months. Secondary outcomes involve ultrasound parameters (median nerve cross-sectional area, blood flow and swelling rate), Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) score. Sensory nerve conduction velocity (SNCV), distal motor latency (DML) of the median nerve as measured by electromyography. The change of ultrasound images and nerve electrophysiology will be evaluated at baseline and 6-month follow-ups. Beyond that, other outcomes will be evaluated at baseline and 1-month, 3-month and 6-month follow-ups. The final statistical analysis of the data will be finished by using intention-to-treat and per-protocol analysis.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e\u003cp\u003eThis study aims to assess the efficacy of various doses of PRP injection in moderate CTS, and to offer guidance for the clinical application of injection therapy.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e\u003cp\u003eChinese Clinical Trial Registry ChiCTR2400094746. Registered on 26 December 2024, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.chictr.org.cn/showproj.html?proj=252770\u003c/span\u003e\u003cspan address=\"https://www.chictr.org.cn/showproj.html?proj=252770\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e","manuscriptTitle":"Efficacy of different doses of Platelet-Rich Plasma for Moderate Carpal Tunnel Syndrome:Study Protocol for a Prospective, Randomized, Controlled trail","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-09 09:21:59","doi":"10.21203/rs.3.rs-6534984/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-10-29T10:22:54+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-07T09:35:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-17T05:56:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"Trials","date":"2025-06-14T07:10:21+00:00","index":"","fulltext":""},{"type":"decision","content":"Revise before peer review","date":"2025-06-12T04:53:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8cc6b25c-6a91-42dc-9449-9f3ede4b70b7","owner":[],"postedDate":"July 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-02T16:01:42+00:00","versionOfRecord":{"articleIdentity":"rs-6534984","link":"https://doi.org/10.1186/s13063-026-09538-1","journal":{"identity":"trials","isVorOnly":false,"title":"Trials"},"publishedOn":"2026-02-25 15:58:34","publishedOnDateReadable":"February 25th, 2026"},"versionCreatedAt":"2025-07-09 09:21:59","video":"","vorDoi":"10.1186/s13063-026-09538-1","vorDoiUrl":"https://doi.org/10.1186/s13063-026-09538-1","workflowStages":[]},"version":"v1","identity":"rs-6534984","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6534984","identity":"rs-6534984","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}