Electroacupuncture Treatment for Sarcopenia: Study Protocol for a Randomized Controlled Trial

Electroacupuncture Treatment for Sarcopenia: Study Protocol for a Randomized Controlled Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Electroacupuncture Treatment for Sarcopenia: Study Protocol for a Randomized Controlled Trial Hao Li, Li Zhou, Xin Zhang, Qian Wen, Li Tian, Han Yang, Xirong Chen, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4109912/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Introduction: Sarcopenia is a disease primarily characterized by age-related loss of skeletal muscle mass, muscle strength, and/or decline in physical performance. Sarcopenia has an insidious onset which can cause functional impairment in the body and increase the risk of falls and disability in the elderly. It significantly increases the likelihood of fractures and mortality, severely impairing the quality of life and health of the elderly people. This disease poses a heavy burden on the healthcare system and society in our country, and currently, there are limited clinical intervention strategies for sarcopenia. This study aims to explore the clinical efficacy and safety of electroacupuncture in treating sarcopenia. Methods and Analysis: In this parallel-design, randomized, sham-controlled trial, a total of 168 elderly sarcopenia patients will be randomly assigned in a 1:1 ratio to receive either electroacupuncture (EA) or sham electroacupuncture (sEA) treatment. The acupuncture points used in the study are Hegu (LI4), Shousanli (LI10), Quchi (LI11), Binao (LI14), Futu (ST32), Liangqiu (ST34), Zusanli (ST36), and Jiexi (ST41). The participants will receive EA or sEA treatment three times per week for eight weeks. The primary outcome measure is the change in grip strength (GS) of the patients after the eight-week treatment. The secondary outcome measures include the changes in grip strength at the fourth and twentieth weeks, changes in appendicular skeletal muscle mass index (ASMI), the Short Physical Performance Battery (SPPB) score, the physical activity level (PAL) assessed by the International Physical Activity Questionnaire (IPAQ), assessment of expectations regarding the efficacy of acupuncture, patient subjective evaluation of efficacy, and evaluation of blinding efficacy of acupuncture. All statistical analyses will be conducted according to the intention-to-treat principle and as per the study protocol. Ethics and Dissemination: This study protocol was reviewed and approved by the Institutional Review Board of West China Hospital of Sichuan University (permission number: 2023-525). The participants will provide written informed consent to participate in this study. Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2300079294. electroacupuncture sarcopenia randomized controlled trial Figures Figure 1 Figure 2 1 Introduction Sarcopenia (SP), also known as muscle atrophy or muscle loss, is an age-related disease characterized by a decline in skeletal muscle mass, muscle strength, and/or physical performance. The prevalence of sarcopenia is estimated to be 5–13% in the 60-70-year-old population, and 11–50% in those over 80 years old( 1 ). The prevalence of sarcopenia in the elderly population in Asia ranges from 5.5–25.7%( 2 ), and in China, the prevalence in community-dwelling elderly males is 12.9% and 11.2% in females( 3 ). Sarcopenia is insidious in the onset which can lead to functional impairment, increasing the risk of falls and disability in the elderly, significantly increasing the likelihood of fractures( 4 ), increasing the risk of death, and severely compromising the quality of life and health of the elderly, placing a heavy burden on China's healthcare system and society. Currently, there are limited clinical intervention options for sarcopenia; therefore, exploring effective treatment strategies for sarcopenia will provide strong evidence to support the management of this disease. Current treatment approaches for sarcopenia can be divided into pharmacological and non-pharmacological treatments. Medications mainly include vitamin D, testosterone, and selective estrogen receptor modulators. Supplementation with vitamin D has no significant effect on improving the muscle loss index in community-dwelling older adults( 5 ). Testosterone supplementation can increase muscle mass in patients with chronic diseases; however, current evidence does not indicate that these patients can improve muscle function through testosterone supplementation( 6 ). At present, there is no mature evidence for pharmacological intervention in sarcopenia( 7 ). Non-pharmacological treatment options mainly include resistance-based exercise training and nutritional supplementation. Exercise can effectively improve muscle strength, lower limb muscle mass, and physical fitness in elderly individuals with sarcopenia( 8 ). In addition, resistance training and various forms of exercise are the preferred options for improving muscle strength, but their impact on upper limb muscle mass is limited, and due to the heterogeneity of exercise modalities, duration, and intensity, training outcomes are not entirely consistent. Older adults may not be able to adequately participate in related functional exercises due to their own illnesses or age-related factors, and further research is needed( 9 , 10 , 11 ). Some evidence suggests that adequate intake of protein, antioxidants, and long-chain polyunsaturated fatty acids may be beneficial for individuals with sarcopenia( 12 ). However, methodological limitations in research restrict the strength of this evidence. In summary, there are currently some shortcomings in the treatment system for sarcopenia, limiting the effective management of this disease, and further enrichment and improvement are needed. The clinical value and effects of acupuncture in the treatment of sarcopenia are gradually being recognized. Acupuncture at acupoints such as "Zusanli" can improve walking speed and lower limb functional scores in elderly patients with sarcopenia( 13 ). Electroacupuncture can improve muscle mass, muscle strength, and mobility in elderly patients with sarcopenia( 14 ). Electroacupuncture combined with oral essential amino acids for 12 weeks can increase skeletal muscle mass in elderly sarcopenic obese patients compared to oral essential amino acids alone( 15 ). However, due to methodological flaws in study design, such as lack of allocation concealment, failure to implement blinding, or not assessing skeletal muscle function, it is not yet possible to draw definitive conclusions about the effectiveness of acupuncture in improving muscle mass and function in patients with sarcopenia. Other studies have also shown that acupuncture has no improvement effect on age-related sarcopenia( 16 ). Therefore, more high-quality evidence is needed to further confirm the clinical efficacy of acupuncture in the treatment of sarcopenia. Therefore, we designed a rigorous, randomized controlled clinical study to explore the clinical effects of electroacupuncture treatment on elderly sarcopenia. 2 Methods and Analysis 2.1 Study Design This study is a single-center, randomized controlled trial. Voluntary patients who meet the inclusion criteria will be openly recruited at West China Hospital of Sichuan University. All patients must understand and sign an informed consent form before enrollment. Each center will strictly follow the diagnostic criteria, inclusion criteria, and exclusion criteria to screen cases. After confirming enrollment, a random number will be obtained by applying the random code process until the total number of observed cases is completed, ending the trial. 2.2 Recruitment This trial will be conducted at West China Hospital of Sichuan University. The diagnostic criteria for muscular dystrophy will follow the "2019 Asian Consensus on Muscular Dystrophy Diagnosis." When patients visit the hospital, they will first be provided with informed consent, followed by an evaluation of their condition by professional researchers and completion of a preliminary screening form. Patients who pass the preliminary screening will undergo baseline evaluations and relevant examinations for further selection. Patients who meet the inclusion criteria will be further confirmed for the feasibility of being randomly assigned to either the acupuncture group or the standard treatment group. Figure 1 illustrates the study flowchart. 2.3 Diagnostic Criteria The diagnosis of sarcopenia is based on the "2019 Asian Sarcopenia Diagnosis Consensus" published by the Asian Working Group for Sarcopenia (AWGS). A diagnosis can be made if both points ( 1 ) and ( 2 ) or points ( 1 ) and ( 3 ) are met, or if all three points are met: ( 1 ) Reduced muscle mass: bioelectrical impedance analysis (BIA) with a male ASMI < 7.0 kg/m2 and a female ASMI < 5.7 kg/m2;( 2 ) Decreased muscle strength: male grip strength < 28 kg, female grip strength < 18 kg;( 3 ) Decreased muscle function: Short Physical Performance Battery (SPPB) score ≤ 9. 2.4 Inclusion Criteria ( 1 ) Meets the diagnostic criteria for "sarcopenia" as outlined in the "2019 Asian Sarcopenia Diagnosis Consensus" published by the Asian Working Group for Sarcopenia;( 2 ) Age between 60 and 80 years old, no gender restrictions;( 3 ) Signs the informed consent form and voluntarily participates in this trial. 2.5 Exclusion Criteria ( 1 ) Suffering from severe kidney disease (glomerular filtration rate < 30 mL/min);( 2 ) Suffering from moderate to severe liver function failure (Child-Pugh Class B or C);( 3 ) Suffering from endocrine diseases related to calcium metabolism disorders (excluding osteoporosis);( 4 ) Suffering from neuromuscular diseases;( 5 ) Taking medications that have a significant impact on musculoskeletal function;( 6 ) Suffering from mental illness, cancer (within the past 5 years);( 7 ) Individuals with drug or alcohol dependence or abuse;( 8 ) Patients participating in other clinical trials. 2.6 Withdrawal Criteria ( 1 ) Specialist physicians are responsible for assessing serious adverse reactions that occur during the study, determining whether to continue or terminate the study;( 2 ) During the study, if symptoms worsen or severe complications or other serious diseases occur that require emergency measures;( 3 ) Researchers discover serious safety issues;( 4 ) Patients who cannot continue treatment for various reasons;( 5 ) The trial participant withdraws informed consent. 2.7 Randomization and Masking This study has a single-blind design. Participants will be unaware of their group allocation, which will only be known to the lead investigator and acupuncture physician. The participants are randomly assigned to EA group and sEA group at a 1:1 ratio. The random sequence will be generated and masked by an online response system maintained by the statisticians. Randomization is stratified by site and defined with a block size of 6. All relevant parameters set during the randomization process are saved in the blinding information. When a qualified participant is enrolled, the person responsible for randomization or clinical researchers will apply for a random number using the central randomization system. 2.8 Intervention Electroacupuncture (EA) Group 1) Main Acupoints: Binao (LI14), Quchi (LI11), Shousanli (LI10), Hegu (LI4), Futu (ST32), Liangqiu (ST34), Zusanli (ST36), and Jiexi (ST41). 2) Procedure: Routine disinfection of acupoints. The Hegu (LI4) Point is located on the back of the hand, at the midpoint of the second metacarpal bone on the radial side. Insert a 0.30mm×25mm filiform needle obliquely to a depth of 0.5-1 cun. The Shousanli (LI10) Point is located on the forearm, 2 cun below the transverse crease of the elbow. Insert a 0.30mm×40mm filiform needle vertically to a depth of 1-1.5 cun. The Quchi (LI11) Point is located at the elbow, at the midpoint of the line connecting the cubital fossa and the external epicondyle of the humerus. Insert a 0.30mm×40mm filiform needle vertically to a depth of 1-1.5 cun. The Binao (LI14) Point is located 7 cun above the elbow, on the anterior edge of the deltoid muscle. Insert a 0.30mm×40mm filiform needle vertically to a depth of 1-1.5 cun. The Futu (ST32) Point is located in the anterior thigh area, 6 cun above the bottom of the patella, on the line connecting the anterior superior iliac spine and the lateral edge of the patella. Insert a 0.3mm×50mm filiform needle vertically to a depth of 1–2 cun. The Liangqiu (ST34) Point is located in the anterior thigh area, 2 cun above the bottom of the patella, between the vastus lateralis muscle and the rectus femoris tendon. Insert a 0.30mm×40mm filiform needle vertically to a depth of 1-1.5 cun. The Zusanli (ST36) Point is located on the outer side of the lower leg, 3 cun below the outer knee point, Insert a 0.3mm×50mm filiform needle vertically to a depth of 1–2 cun. The Jiexi (ST41) Point is located in the ankle area, in the central depression in front of the ankle joint, between the long extensor tendon of the big toe and the long extensor tendon of the toes. Insert a 0.30mm×25mm filiform needle vertically to a depth of 0.5-1 cun. Immediately after needling, perform vigorous lifting, thrusting, and twisting techniques. Followed by electroacupuncture stimulation, with one set of electroacupuncture connected to the same side's Quchi (LI11) Point and Hegu (LI4) Point, and another set connected to the same side's Futu (ST32) Point and Zusanli (ST36) Point. A total of 4 sets of electroacupuncture, with a continuous frequency of 2Hz and each electroacupuncture stimulation lasting for 30 minutes. After enrollment, treatment is conducted 3 times per week for 8 weeks. Sham electroacupuncture(sEA) Group 1) Main Acupoint: Same acupoint as the EA Group. 2) Procedure: The Park sham placebo acupuncture device (PSD) is used for the procedure. The PSD is a dull-tipped retractable needle. The acupuncturist inserts the needle into the cannula, and once the blunt tip contacts the skin, the needle retracts into the handle, without penetrating the skin. After the needle insertion is completed, the device is connected to a placebo electroacupuncture device that only has a flashing current indicator light but no actual current output, following the same connection method as the EA group. Observation Period: A total of 21 weeks, including a 1-week baseline period, an 8-week treatment period, and a 12-week follow-up period. The selected acupoints and their locations are shown in Fig. 2 . 2.9 Outcome Measures Primary Outcome Patient's grip strength (GS) change after 8 weeks of treatment: Grip strength of the dominant hand was measured using a dynamometer at both baseline and the end of the 8-week treatment period. Three measurements were taken with a 5-minute rest interval between each measurement. The average of the three measurements was calculated. The grip strength change rate was then calculated using the following formula: Grip Strength Change Rate = (Post-treatment Grip Strength-Pre-treatment Grip Strength)/Pre-treatment Grip Strength × 100%. Secondary Outcomes 1) Patient's grip strength change rate at week 4 and week 20: Grip strength of the dominant hand was measured using a dynamometer at week 4 and week 20. Three measurements were taken with a 5-minute rest interval between each measurement. The average of the three measurements was calculated. The grip strength change rate was then calculated by comparing it to the baseline grip strength. 2) Appendicular Skeletal Muscle Index (ASMI) change rate: Patient's body composition analysis was conducted using the Inbody bioelectrical impedance analysis device (BioSpace, Seoul, Korea). The commonly used SMI was used for evaluation. The SMI change rate was calculated using the following formula: SMI Change Rate = (Post-treatment SMI - Pre-treatment SMI) / Pre-treatment SMI × 100%. 3) Muscle Function Evaluation: The Short Physical Performance Battery (SPPB) was used to evaluate the muscle function of the patients. 4) Daily Function Assessment: The International Physical Activity Questionnaire (IPAQ) will be used for the assessment of It mainly evaluates the frequency and duration of common activities in the past week. Based on the metabolic equivalent tasks (METs) of each activity, weekly energy expenditure is calculated to assess the patient's daily activity level. 5) Subjective Assessment of Treatment Efficacy by Patients: ① Using a Visual Analog Scale (VAS), please rate your subjective perception of the effectiveness of electroacupuncture. A score of 0 indicates no improvement, while a score of 10 indicates complete improvement. ② Ask patients to evaluate whether electroacupuncture is helpful in treating muscle atrophy using a 7-point scale. 6)Serum inflammatory factor levels: Blood samples were collected from patients to measure CRP, IL-6, and TNF-α levels. 7) Expectation Evaluation of Electroacupuncture and Its Correlation with Primary Outcome Measures: ① Do you believe that electroacupuncture treatment will be effective for your condition? Yes, no, unsure. ② Do you think electroacupuncture will be helpful in improving symptoms such as muscle weakness? Yes, no, unsure. ③ Using a Visual Analog Scale (VAS), please rate your expectation of the effectiveness of electroacupuncture. A score of 0 indicates no improvement, while a score of 10 indicates complete improvement. 8) Evaluation of Electroacupuncture Blinding: Inform the patients about two treatment methods, one being electroacupuncture and the other being placebo electroacupuncture. Then ask the patients to choose: Do you think you received electroacupuncture treatment? Don't know, yes, no. Simultaneously evaluate the effectiveness of electroacupuncture blinding and its correlation with the patients' experience with electroacupuncture. The outcome measurement time points are provided in detail in Table 1 . Table 1 Details of the planned visit schedule. Stage Baseline period Treatment period Follow-up period Time point (week) -2 4 8 12 16 20 Enrolment Eligibility screen X Informed consent X Demographic characteristics X Medical history X Expectation of electroacupuncture X Assessments Grip strength X X X X X X ASMI X X X X X X SPPB X X X X X X Daily Function X X X X X X Gut microbiota X X X Serum untargeted metabolomics sequencing X X X Serum inflammatory factor levels X X X Usage of emergency drug or surgery X Self-evaluation of therapeutic effects X Rate of adverse events X 2.10 Safety Evaluation EA-related safety evaluation during treatment includes the documentation of broken needles, fainting due to needles, intolerable pinprick pain, local hematoma, infection, abscess, and other incidences of discomfort after pinprick. Adverse events will be recorded by the acupuncture physician on a standardized form. 2.11 Sample Size Based on the results of previous similar studies (Soares Mendes Damasceno G, et al. Acupuncture Treatment in Elderly People with Sarcopenia: Effects on the Strength and Inflammatory Mediators. J Aging Res. 2019 Jan 27;2019:8483576), we used a two-sided test of difference and calculated the sample size using PASS 15 software. The average grip strength for the acupuncture group was 24.4 with a standard deviation of 8.59, while the control group had an average grip strength of 21.5 with a standard deviation of 4.51. With α = 0.05, β = 0.2, and Power = 0.8, each group required 70 participants. Considering a 20% dropout rate causing sample size loss, each group needed 84 participants, totaling 168 participants required for the study. 2.12 Statistical Analysis The data will be analyzed by R software (R Foundation), version 4.2.1. An independent statistician who does not know the group assignments will run the statistical analysis. Continuous variables will be described as mean ± SD with a 95% CI in a normal distribution and median (range) in abnormal distribution, while categorical variables will be represented by numbers (percentages). All statistical tests will be two-sided, and a p value < 0.05 will be considered statistically significant. All analyses will be performed according to intention-to-treat (ITT) protocol. Participants who finish the baseline assessment of primary outcome and receive at least one session of either EA or sEA will be included in the ITT analysis. The missing values will be imputed by multiple imputations. Per-protocol population analysis will be also performed, for participants who have finished at least 80% of the treatment protocol after randomization. The primary analysis used a linear regression model to test whether acupuncture improved GS more than sham acupuncture. Secondary analyses were done for other outcomes. Continuous data (SMI, SPPB, IPAQ scores, serum inflammatory factor levels; and patient subjective evaluation of efficacy) were analyzed using the same linear regression model. Categorical and count datawill be compared by the χ2 test or Fisher’s exact test. Discussion Sarcopenia in the elderly can be classified within the categories of "Wei Syndrome" and "Wei Bi" in traditional Chinese medicine (TCM), with the affected areas being the limbs and the root cause in the organs. The Yellow Emperor’s Inner Canon records that Yangming meridians must be focused in treating Wei Syndrome. Foot Yangming meridian is related to the stomach, which is responsible for receiving, digesting, and transforming nutrients from food and water, and is closely connected with the the Spleen Meridian of Foot Taiyin, mutually influencing each other. Hand Yangming meridian is related to the large intestine, which processes waste and is responsible for "fluids" that nourish the organs, bones, and joints, and moisturize the whole body. If Yangming is deficient, the generation and transformation of essence and blood will be insufficient, leading to abnormalities in receiving and transforming nutrients. This results in the body's inability to receive nutrients and irrigate the surrounding areas, causing malnourishment of muscles and tendons, and the manifestation of "Wei Syndrome" in the limbs. Focusing on Yangming in the treatment of sarcopenia in the elderly emphasizes the importance of regulating and protecting the spleen and stomach. By stimulating the Yangming Meridian, the spleen and stomach can be regulated, helping transport the essence of food and water, replenishing qi and blood, improving the state of inadequate intake and absorption, and activating muscle function. In electroacupuncture treatment for sarcopenia in the elderly, the Zusanli acupoint on the Yangming Meridian is the fundamental and essential acupoint in the treatment. The pathogenesis of sarcopenia is complex, involving factors such as age-related anabolic hormone changes, loss of motor neurons, apoptosis of muscle satellite cells, and mitochondrial dysfunction. Among these factors, inflammation plays a crucial role in the pathophysiology of sarcopenia. Studies have shown that the inflammatory marker C-reactive protein (CRP) is negatively correlated with muscle strength and mass( 17 ). Elevated levels of high-sensitivity CRP (hs-CRP), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) are significant risk factors for sarcopenia( 18 ). A cohort study of Chinese subjects found that high levels of inflammatory markers IL-6 and TNF-α were associated with an increased risk of sarcopenia, and logistic regression analysis showed that high levels of TNF-α (11.15 pg/ml) increased the risk of sarcopenia by 7.6 times( 19 ). Elevated serum IL-6 and TNF-α levels can not only predict the occurrence of sarcopenia but also predict adverse clinical outcomes such as disability and death( 20 ). A meta-analysis showed that high levels of CRP, IL-6, and TNF-α were negatively correlated with grip strength, knee extension strength, and muscle mass, indicating that high levels of circulating inflammatory markers are significantly associated with lower skeletal muscle strength and mass( 21 ). It is still unclear whether electroacupuncture can exert its clinical effects on sarcopenia treatment by modulating the levels of inflammatory mediators. Therefore, this study focuses on elderly sarcopenia patients and adopts a randomized controlled trial design. In addition to exploring the clinical effects of electroacupuncture treatment for elderly sarcopenia, we aim to preliminarily investigate the potential underlying mechanisms involving and inflammatory responses. Our goal is to provide a new treatment option for elderly sarcopenia patients, break through therapeutic bottlenecks, and ultimately benefit numerous patients. Declarations Ethics and Dissemination This study protocol was reviewed and approved by the Institutional Review Board of West China Hospital of Sichuan University. The participants will provide written informed consent to participate in this study. Conflict of Interest The authors declare that the research will be conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Author Contributions HL and LZ contributed equally to this article. HL, LYL and LZ conceived the idea for this study. XZ participated in the design and drafted the manuscript. QW and YH will be responsible for recruiting subjects. CX and YJ are responsible for collecting the data. LT, BMZ and NL contributed to the final version of the manuscript. LZ and LYL will be responsible for monitoring this study. All authors contributed to manuscript revision and have read and approved the submitted version. Funding This study is supported by the Sichuan Science and Technology Program (grant number: 2023YFS0247). Acknowledgments We thank all the participants in the study, including the participants, statisticians, acupuncturists, and evaluators, as well as West China Hospital of Sichuan University for their support. References Haase CB, Brodersen JB, Bülow J. Sarcopenia: early prevention or overdiagnosis? BMJ. 2022;376:e052592. Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, et al. Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment. J Am Med Dir Assoc. 2020;21(3):300–e72. Chen X, Hou L, Zhang Y, Dong B. Analysis of the Prevalence of Sarcopenia and Its Risk Factors in the Elderly in the Chengdu Community. J Nutr Health Aging. 2021;25(5):600–5. Yoshimura N, Muraki S, Oka H, Iidaka T, Kodama R, Kawaguchi H, et al. Is osteoporosis a predictor for future sarcopenia or vice versa? Four-year observations between the second and third ROAD study surveys. Osteoporos Int. 2017;28(1):189–99. Prokopidis K, Giannos P, Katsikas Triantafyllidis K, Kechagias KS, Mesinovic J, Witard OC, et al. Effect of vitamin D monotherapy on indices of sarcopenia in community-dwelling older adults: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2022;13(3):1642–52. Correa C, Bieger P, Perry IS, Souza GC. Testosterone Supplementation on Sarcopenia Components in Chronic Patients: A Systematic Review and Meta-Analysis. Curr Pharm Des. 2022;28(7):586–94. Rooks D, Roubenoff R. Development of Pharmacotherapies for the Treatment of Sarcopenia. J Frailty Aging. 2019;8(3):120–30. Valdés-Badilla P, Guzmán-Muñoz E, Hernandez-Martinez J, Núñez-Espinosa C, Delgado-Floody P, Herrera-Valenzuela T, et al. Effectiveness of elastic band training and group-based dance on physical-functional performance in older women with sarcopenia: a pilot study. BMC Public Health. 2023;23(1):2113. Wang H, Huang WY, Zhao Y. Efficacy of Exercise on Muscle Function and Physical Performance in Older Adults with Sarcopenia: An Updated Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2022;19(13). Vlietstra L, Hendrickx W, Waters DL. Exercise interventions in healthy older adults with sarcopenia: A systematic review and meta-analysis. Australas J Ageing. 2018;37(3):169–83. Chen N, He X, Feng Y, Ainsworth BE, Liu Y. Effects of resistance training in healthy older people with sarcopenia: a systematic review and meta-analysis of randomized controlled trials. Eur Rev Aging Phys Act. 2021;18(1):23. Robinson SM, Reginster JY, Rizzoli R, Shaw SC, Kanis JA, Bautmans I, et al. Does nutrition play a role in the prevention and management of sarcopenia? Clin Nutr. 2018;37(4):1121–32. Ma SF, Lv WY, Zhu QY, Li HJ, Li JJ, Shi Q, et al. [Electroacupuncture at acupoints of yangming meridians for sarcopenia: a randomized controlled trial]. Zhongguo Zhen Jiu. 2023;43(10):1114–7. Zhu ZW, Tang CL, Li XH, Yang ZX, Yang YH, Pang F, et al. [Effects of electroacupuncture on proangiogenesis process and protein turnover in a mouse model of sarcopenia]. Zhen Ci Yan Jiu. 2020;45(12):973–9. Zhou X, Xing B, He G, Lyu X, Zeng Y. The Effects of Electrical Acupuncture and Essential Amino Acid Supplementation on Sarcopenic Obesity in Male Older Adults: A Randomized Control Study. Obes Facts. 2018;11(4):327–34. Soares Mendes Damasceno G, Teixeira T, de Souza VC, Neiva TS, Prudente Pereira K, Teles Landim MF, et al. Acupuncture Treatment in Elderly People with Sarcopenia: Effects on the Strength and Inflammatory Mediators. J Aging Res. 2019;2019:8483576. Hida T, Imagama S, Ando K, Kobayashi K, Muramoto A, Ito K, et al. Sarcopenia and physical function are associated with inflammation and arteriosclerosis in community-dwelling people: The Yakumo study. Mod Rheumatol. 2018;28(2):345–50. Rong YD, Bian AL, Hu HY, Ma Y, Zhou XZ. Study on relationship between elderly sarcopenia and inflammatory cytokine IL-6, anti-inflammatory cytokine IL-10. BMC Geriatr. 2018;18(1):308. Li CW, Yu K, Shyh-Chang N, Li GX, Jiang LJ, Yu SL, et al. Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention. J Cachexia Sarcopenia Muscle. 2019;10(3):586–600. Grosicki GJ, Barrett BB, Englund DA, Liu C, Travison TG, Cederholm T, et al. Circulating Interleukin-6 Is Associated with Skeletal Muscle Strength, Quality, and Functional Adaptation with Exercise Training in Mobility-Limited Older Adults. J Frailty Aging. 2020;9(1):57–63. Tuttle CSL, Thang LAN, Maier AB. Markers of inflammation and their association with muscle strength and mass: A systematic review and meta-analysis. Ageing Res Rev. 2020;64:101185. Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterial1.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 26 Jun, 2024 Editor assigned by journal 30 May, 2024 Editor invited by journal 18 Mar, 2024 Submission checks completed at journal 18 Mar, 2024 First submitted to journal 15 Mar, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4109912","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":280930402,"identity":"1c4279b1-b3b2-4024-aab2-5d4a9d4fefe9","order_by":0,"name":"Hao Li","email":"","orcid":"","institution":"Division of internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Li","suffix":""},{"id":280930405,"identity":"b8c635b9-85b8-414d-bc70-a0b390581623","order_by":1,"name":"Li Zhou","email":"","orcid":"","institution":"Core Facilities of West China Hospital, Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Zhou","suffix":""},{"id":280930406,"identity":"9f195849-62ed-4bf7-bca4-a744ca8242fe","order_by":2,"name":"Xin Zhang","email":"","orcid":"","institution":"Division of internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Zhang","suffix":""},{"id":280930408,"identity":"4c6c39c2-5849-4760-8995-42cdd16ae88d","order_by":3,"name":"Qian Wen","email":"","orcid":"","institution":"Division of internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Wen","suffix":""},{"id":280930412,"identity":"89e5e6d5-ceab-4f4a-9905-61619f7a59ce","order_by":4,"name":"Li Tian","email":"","orcid":"","institution":"Department of Endocrinology and Metabolism, Laboratory of Endocrinology and Metabolism, Sichuan University West China Hospital","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Tian","suffix":""},{"id":280930415,"identity":"528d97aa-cddf-4244-8c06-e3fce08dbe6b","order_by":5,"name":"Han Yang","email":"","orcid":"","institution":"Division of internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Han","middleName":"","lastName":"Yang","suffix":""},{"id":280930423,"identity":"27a43437-9a49-48eb-aaa6-b31904f791ea","order_by":6,"name":"Xirong Chen","email":"","orcid":"","institution":"Department of Rehabilitation Medicine, The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Xirong","middleName":"","lastName":"Chen","suffix":""},{"id":280930425,"identity":"3ea259eb-fa8c-4605-b9bb-2a963957916f","order_by":7,"name":"Jinghan Yuan","email":"","orcid":"","institution":"Division of internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Regenerative Medicine Research Center, West China Hospital, Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Jinghan","middleName":"","lastName":"Yuan","suffix":""},{"id":280930427,"identity":"7e57c261-b385-456b-b033-fb92f297c2de","order_by":8,"name":"Ning Li","email":"","orcid":"","institution":"Division of internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Ning","middleName":"","lastName":"Li","suffix":""},{"id":280930428,"identity":"ce7bcc4b-72cc-4162-a7b5-c8745246ac3a","order_by":9,"name":"Bingmei Zhu","email":"","orcid":"","institution":"Division of internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Regenerative Medicine Research Center, West China Hospital, Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Bingmei","middleName":"","lastName":"Zhu","suffix":""},{"id":280930430,"identity":"492dcd3a-7be7-44d8-bc5e-c20a5186bf96","order_by":10,"name":"Lin Zhang","email":"","orcid":"","institution":"General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Zhang","suffix":""},{"id":280930431,"identity":"cb8e3973-7aed-4e64-821b-be7ef806aff0","order_by":11,"name":"Lingyun Lu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIie3RsWrDMBCA4QuCy6LG6wWC8woGg6c+jIQhkxsCgeIh0ECCPITGr5Ixo4xBk5I5Qwd76dxsmUrduSVytw76Zv2cTgLwvH8Ih2XbfuSfLxhsqkbkK3cy4pbFZLUYkUmjxhp3ElKG9KC0CCFLxu2W9bgYP9XRWL3NEXSSyzVCUOyEY5e9bBbn9yWy9ewijxMgezo4pug4omc2UKDNRVqEiJ4cCYmEOH4nUi2kYn2SrEtULRWkCP0SbtLukWcxkmEkrOHOXabFpuq+8jGcluX1estXYVC83k9+4H877nme5/3qC1yOS/jN2FqDAAAAAElFTkSuQmCC","orcid":"","institution":"Division of internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University","correspondingAuthor":true,"prefix":"","firstName":"Lingyun","middleName":"","lastName":"Lu","suffix":""}],"badges":[],"createdAt":"2024-03-15 18:59:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4109912/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4109912/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53184663,"identity":"33a1066d-eaa8-492b-bf19-b74dac3605ed","added_by":"auto","created_at":"2024-03-21 16:06:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":241298,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the study procedure.\u003c/p\u003e","description":"","filename":"F1.png","url":"https://assets-eu.researchsquare.com/files/rs-4109912/v1/cdc8570981f04e37ddd19418.png"},{"id":53186019,"identity":"40e9d44c-7ce0-43f7-98a5-1326185cff72","added_by":"auto","created_at":"2024-03-21 16:14:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":461590,"visible":true,"origin":"","legend":"\u003cp\u003eLocalisation of acupoints.\u003c/p\u003e","description":"","filename":"fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-4109912/v1/a1c1e00645f6ff54647626b3.png"},{"id":53186532,"identity":"6e3f804e-5ea3-4c07-9a52-e3f4e162130a","added_by":"auto","created_at":"2024-03-21 16:22:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":584274,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4109912/v1/8249659c-d5a6-468d-8821-3935553afb79.pdf"},{"id":53184661,"identity":"aa435c1d-af80-4e85-a608-2b9c3a8a895a","added_by":"auto","created_at":"2024-03-21 16:06:31","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":52720,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4109912/v1/35c0c49db32ef7289c3fe149.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Electroacupuncture Treatment for Sarcopenia: Study Protocol for a Randomized Controlled Trial","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eSarcopenia (SP), also known as muscle atrophy or muscle loss, is an age-related disease characterized by a decline in skeletal muscle mass, muscle strength, and/or physical performance. The prevalence of sarcopenia is estimated to be 5\u0026ndash;13% in the 60-70-year-old population, and 11\u0026ndash;50% in those over 80 years old(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The prevalence of sarcopenia in the elderly population in Asia ranges from 5.5\u0026ndash;25.7%(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), and in China, the prevalence in community-dwelling elderly males is 12.9% and 11.2% in females(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Sarcopenia is insidious in the onset which can lead to functional impairment, increasing the risk of falls and disability in the elderly, significantly increasing the likelihood of fractures(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), increasing the risk of death, and severely compromising the quality of life and health of the elderly, placing a heavy burden on China's healthcare system and society. Currently, there are limited clinical intervention options for sarcopenia; therefore, exploring effective treatment strategies for sarcopenia will provide strong evidence to support the management of this disease.\u003c/p\u003e \u003cp\u003eCurrent treatment approaches for sarcopenia can be divided into pharmacological and non-pharmacological treatments. Medications mainly include vitamin D, testosterone, and selective estrogen receptor modulators. Supplementation with vitamin D has no significant effect on improving the muscle loss index in community-dwelling older adults(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Testosterone supplementation can increase muscle mass in patients with chronic diseases; however, current evidence does not indicate that these patients can improve muscle function through testosterone supplementation(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). At present, there is no mature evidence for pharmacological intervention in sarcopenia(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Non-pharmacological treatment options mainly include resistance-based exercise training and nutritional supplementation. Exercise can effectively improve muscle strength, lower limb muscle mass, and physical fitness in elderly individuals with sarcopenia(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In addition, resistance training and various forms of exercise are the preferred options for improving muscle strength, but their impact on upper limb muscle mass is limited, and due to the heterogeneity of exercise modalities, duration, and intensity, training outcomes are not entirely consistent. Older adults may not be able to adequately participate in related functional exercises due to their own illnesses or age-related factors, and further research is needed(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Some evidence suggests that adequate intake of protein, antioxidants, and long-chain polyunsaturated fatty acids may be beneficial for individuals with sarcopenia(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). However, methodological limitations in research restrict the strength of this evidence. In summary, there are currently some shortcomings in the treatment system for sarcopenia, limiting the effective management of this disease, and further enrichment and improvement are needed.\u003c/p\u003e \u003cp\u003eThe clinical value and effects of acupuncture in the treatment of sarcopenia are gradually being recognized. Acupuncture at acupoints such as \"Zusanli\" can improve walking speed and lower limb functional scores in elderly patients with sarcopenia(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Electroacupuncture can improve muscle mass, muscle strength, and mobility in elderly patients with sarcopenia(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Electroacupuncture combined with oral essential amino acids for 12 weeks can increase skeletal muscle mass in elderly sarcopenic obese patients compared to oral essential amino acids alone(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). However, due to methodological flaws in study design, such as lack of allocation concealment, failure to implement blinding, or not assessing skeletal muscle function, it is not yet possible to draw definitive conclusions about the effectiveness of acupuncture in improving muscle mass and function in patients with sarcopenia. Other studies have also shown that acupuncture has no improvement effect on age-related sarcopenia(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Therefore, more high-quality evidence is needed to further confirm the clinical efficacy of acupuncture in the treatment of sarcopenia.\u003c/p\u003e \u003cp\u003eTherefore, we designed a rigorous, randomized controlled clinical study to explore the clinical effects of electroacupuncture treatment on elderly sarcopenia.\u003c/p\u003e"},{"header":"2 Methods and Analysis","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Design\u003c/h2\u003e \u003cp\u003eThis study is a single-center, randomized controlled trial. Voluntary patients who meet the inclusion criteria will be openly recruited at West China Hospital of Sichuan University. All patients must understand and sign an informed consent form before enrollment. Each center will strictly follow the diagnostic criteria, inclusion criteria, and exclusion criteria to screen cases. After confirming enrollment, a random number will be obtained by applying the random code process until the total number of observed cases is completed, ending the trial.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Recruitment\u003c/h2\u003e \u003cp\u003eThis trial will be conducted at West China Hospital of Sichuan University. The diagnostic criteria for muscular dystrophy will follow the \"2019 Asian Consensus on Muscular Dystrophy Diagnosis.\" When patients visit the hospital, they will first be provided with informed consent, followed by an evaluation of their condition by professional researchers and completion of a preliminary screening form. Patients who pass the preliminary screening will undergo baseline evaluations and relevant examinations for further selection. Patients who meet the inclusion criteria will be further confirmed for the feasibility of being randomly assigned to either the acupuncture group or the standard treatment group. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates the study flowchart.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Diagnostic Criteria\u003c/h2\u003e \u003cp\u003eThe diagnosis of sarcopenia is based on the \"2019 Asian Sarcopenia Diagnosis Consensus\" published by the Asian Working Group for Sarcopenia (AWGS). A diagnosis can be made if both points (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) and (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) or points (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) and (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) are met, or if all three points are met:\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Reduced muscle mass: bioelectrical impedance analysis (BIA) with a male ASMI\u0026thinsp;\u0026lt;\u0026thinsp;7.0 kg/m2 and a female ASMI\u0026thinsp;\u0026lt;\u0026thinsp;5.7 kg/m2;(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Decreased muscle strength: male grip strength\u0026thinsp;\u0026lt;\u0026thinsp;28 kg, female grip strength\u0026thinsp;\u0026lt;\u0026thinsp;18 kg;(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Decreased muscle function: Short Physical Performance Battery (SPPB) score\u0026thinsp;\u0026le;\u0026thinsp;9.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Inclusion Criteria\u003c/h2\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Meets the diagnostic criteria for \"sarcopenia\" as outlined in the \"2019 Asian Sarcopenia Diagnosis Consensus\" published by the Asian Working Group for Sarcopenia;(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Age between 60 and 80 years old, no gender restrictions;(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Signs the informed consent form and voluntarily participates in this trial.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Exclusion Criteria\u003c/h2\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Suffering from severe kidney disease (glomerular filtration rate\u0026thinsp;\u0026lt;\u0026thinsp;30 mL/min);(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Suffering from moderate to severe liver function failure (Child-Pugh Class B or C);(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Suffering from endocrine diseases related to calcium metabolism disorders (excluding osteoporosis);(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Suffering from neuromuscular diseases;(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Taking medications that have a significant impact on musculoskeletal function;(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Suffering from mental illness, cancer (within the past 5 years);(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Individuals with drug or alcohol dependence or abuse;(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) Patients participating in other clinical trials.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Withdrawal Criteria\u003c/h2\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Specialist physicians are responsible for assessing serious adverse reactions that occur during the study, determining whether to continue or terminate the study;(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) During the study, if symptoms worsen or severe complications or other serious diseases occur that require emergency measures;(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Researchers discover serious safety issues;(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Patients who cannot continue treatment for various reasons;(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) The trial participant withdraws informed consent.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.7 Randomization and Masking\u003c/h2\u003e \u003cp\u003eThis study has a single-blind design. Participants will be unaware of their group allocation, which will only be known to the lead investigator and acupuncture physician. The participants are randomly assigned to EA group and sEA group at a 1:1 ratio. The random sequence will be generated and masked by an online response system maintained by the statisticians. Randomization is stratified by site and defined with a block size of 6. All relevant parameters set during the randomization process are saved in the blinding information. When a qualified participant is enrolled, the person responsible for randomization or clinical researchers will apply for a random number using the central randomization system.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.8 Intervention\u003c/h2\u003e \u003cp\u003e \u003cb\u003eElectroacupuncture (EA) Group\u003c/b\u003e \u003c/p\u003e \u003cp\u003e1) Main Acupoints: Binao (LI14), Quchi (LI11), Shousanli (LI10), Hegu (LI4), Futu (ST32), Liangqiu (ST34), Zusanli (ST36), and Jiexi (ST41).\u003c/p\u003e \u003cp\u003e2) Procedure: Routine disinfection of acupoints. The Hegu (LI4) Point is located on the back of the hand, at the midpoint of the second metacarpal bone on the radial side. Insert a 0.30mm\u0026times;25mm filiform needle obliquely to a depth of 0.5-1 cun. The Shousanli (LI10) Point is located on the forearm, 2 cun below the transverse crease of the elbow. Insert a 0.30mm\u0026times;40mm filiform needle vertically to a depth of 1-1.5 cun. The Quchi (LI11) Point is located at the elbow, at the midpoint of the line connecting the cubital fossa and the external epicondyle of the humerus. Insert a 0.30mm\u0026times;40mm filiform needle vertically to a depth of 1-1.5 cun. The Binao (LI14) Point is located 7 cun above the elbow, on the anterior edge of the deltoid muscle. Insert a 0.30mm\u0026times;40mm filiform needle vertically to a depth of 1-1.5 cun. The Futu (ST32) Point is located in the anterior thigh area, 6 cun above the bottom of the patella, on the line connecting the anterior superior iliac spine and the lateral edge of the patella. Insert a 0.3mm\u0026times;50mm filiform needle vertically to a depth of 1\u0026ndash;2 cun. The Liangqiu (ST34) Point is located in the anterior thigh area, 2 cun above the bottom of the patella, between the vastus lateralis muscle and the rectus femoris tendon. Insert a 0.30mm\u0026times;40mm filiform needle vertically to a depth of 1-1.5 cun. The Zusanli (ST36) Point is located on the outer side of the lower leg, 3 cun below the outer knee point, Insert a 0.3mm\u0026times;50mm filiform needle vertically to a depth of 1\u0026ndash;2 cun. The Jiexi (ST41) Point is located in the ankle area, in the central depression in front of the ankle joint, between the long extensor tendon of the big toe and the long extensor tendon of the toes. Insert a 0.30mm\u0026times;25mm filiform needle vertically to a depth of 0.5-1 cun. Immediately after needling, perform vigorous lifting, thrusting, and twisting techniques. Followed by electroacupuncture stimulation, with one set of electroacupuncture connected to the same side's Quchi (LI11) Point and Hegu (LI4) Point, and another set connected to the same side's Futu (ST32) Point and Zusanli (ST36) Point. A total of 4 sets of electroacupuncture, with a continuous frequency of 2Hz and each electroacupuncture stimulation lasting for 30 minutes. After enrollment, treatment is conducted 3 times per week for 8 weeks.\u003c/p\u003e \u003cp\u003e \u003cb\u003eSham electroacupuncture(sEA) Group\u003c/b\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e1) Main Acupoint: Same acupoint as the EA Group.\u003c/h3\u003e\n\u003cp\u003e2) Procedure: The Park sham placebo acupuncture device (PSD) is used for the procedure. The PSD is a dull-tipped retractable needle. The acupuncturist inserts the needle into the cannula, and once the blunt tip contacts the skin, the needle retracts into the handle, without penetrating the skin. After the needle insertion is completed, the device is connected to a placebo electroacupuncture device that only has a flashing current indicator light but no actual current output, following the same connection method as the EA group.\u003c/p\u003e \u003cp\u003eObservation Period: A total of 21 weeks, including a 1-week baseline period, an 8-week treatment period, and a 12-week follow-up period.\u003c/p\u003e \u003cp\u003eThe selected acupoints and their locations are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e2.9 Outcome Measures\u003c/h2\u003e \u003cp\u003e \u003cb\u003ePrimary Outcome\u003c/b\u003e \u003c/p\u003e \u003cp\u003ePatient's grip strength (GS) change after 8 weeks of treatment: Grip strength of the dominant hand was measured using a dynamometer at both baseline and the end of the 8-week treatment period. Three measurements were taken with a 5-minute rest interval between each measurement. The average of the three measurements was calculated. The grip strength change rate was then calculated using the following formula: Grip Strength Change Rate = (Post-treatment Grip Strength-Pre-treatment Grip Strength)/Pre-treatment Grip Strength \u0026times; 100%.\u003c/p\u003e \u003cp\u003e \u003cb\u003eSecondary Outcomes\u003c/b\u003e \u003c/p\u003e \u003cp\u003e1) Patient's grip strength change rate at week 4 and week 20: Grip strength of the dominant hand was measured using a dynamometer at week 4 and week 20. Three measurements were taken with a 5-minute rest interval between each measurement. The average of the three measurements was calculated. The grip strength change rate was then calculated by comparing it to the baseline grip strength.\u003c/p\u003e \u003cp\u003e2) Appendicular Skeletal Muscle Index (ASMI) change rate: Patient's body composition analysis was conducted using the Inbody bioelectrical impedance analysis device (BioSpace, Seoul, Korea). The commonly used SMI was used for evaluation. The SMI change rate was calculated using the following formula: SMI Change Rate = (Post-treatment SMI - Pre-treatment SMI) / Pre-treatment SMI \u0026times; 100%.\u003c/p\u003e \u003cp\u003e3) Muscle Function Evaluation: The Short Physical Performance Battery (SPPB) was used to evaluate the muscle function of the patients.\u003c/p\u003e \u003cp\u003e4) Daily Function Assessment: The International Physical Activity Questionnaire (IPAQ) will be used for the assessment of It mainly evaluates the frequency and duration of common activities in the past week. Based on the metabolic equivalent tasks (METs) of each activity, weekly energy expenditure is calculated to assess the patient's daily activity level.\u003c/p\u003e \u003cp\u003e5) Subjective Assessment of Treatment Efficacy by Patients: ① Using a Visual Analog Scale (VAS), please rate your subjective perception of the effectiveness of electroacupuncture. A score of 0 indicates no improvement, while a score of 10 indicates complete improvement. ② Ask patients to evaluate whether electroacupuncture is helpful in treating muscle atrophy using a 7-point scale.\u003c/p\u003e \u003cp\u003e6)Serum inflammatory factor levels: Blood samples were collected from patients to measure CRP, IL-6, and TNF-α levels.\u003c/p\u003e \u003cp\u003e7) Expectation Evaluation of Electroacupuncture and Its Correlation with Primary Outcome Measures: ① Do you believe that electroacupuncture treatment will be effective for your condition? Yes, no, unsure. ② Do you think electroacupuncture will be helpful in improving symptoms such as muscle weakness? Yes, no, unsure. ③ Using a Visual Analog Scale (VAS), please rate your expectation of the effectiveness of electroacupuncture. A score of 0 indicates no improvement, while a score of 10 indicates complete improvement.\u003c/p\u003e \u003cp\u003e8) Evaluation of Electroacupuncture Blinding: Inform the patients about two treatment methods, one being electroacupuncture and the other being placebo electroacupuncture. Then ask the patients to choose: Do you think you received electroacupuncture treatment? Don't know, yes, no. Simultaneously evaluate the effectiveness of electroacupuncture blinding and its correlation with the patients' experience with electroacupuncture.\u003c/p\u003e \u003cp\u003eThe outcome measurement time points are provided in detail in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\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\u003eDetails of the planned visit schedule.\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 \u003cp\u003eStage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline period\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eTreatment period\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eFollow-up period\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime point (week)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20\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\u003eX\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\u003eX\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\u003eDemographic characteristics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\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\u003eMedical history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\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\u003eExpectation of electroacupuncture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\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\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eAssessments\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrip strength\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSPPB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDaily Function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGut microbiota\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eX\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 \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum untargeted metabolomics sequencing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eX\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 \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum inflammatory factor levels\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eX\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 \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUsage of emergency drug or surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c7\" namest=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelf-evaluation of therapeutic effects\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c7\" namest=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRate of adverse events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c7\" namest=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e2.10 Safety Evaluation\u003c/h2\u003e \u003cp\u003eEA-related safety evaluation during treatment includes the documentation of broken needles, fainting due to needles, intolerable pinprick pain, local hematoma, infection, abscess, and other incidences of discomfort after pinprick. Adverse events will be recorded by the acupuncture physician on a standardized form.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e2.11 Sample Size\u003c/h2\u003e \u003cp\u003eBased on the results of previous similar studies (Soares Mendes Damasceno G, et al. Acupuncture Treatment in Elderly People with Sarcopenia: Effects on the Strength and Inflammatory Mediators. J Aging Res. 2019 Jan 27;2019:8483576), we used a two-sided test of difference and calculated the sample size using PASS 15 software. The average grip strength for the acupuncture group was 24.4 with a standard deviation of 8.59, while the control group had an average grip strength of 21.5 with a standard deviation of 4.51. With α\u0026thinsp;=\u0026thinsp;0.05, β\u0026thinsp;=\u0026thinsp;0.2, and Power\u0026thinsp;=\u0026thinsp;0.8, each group required 70 participants. Considering a 20% dropout rate causing sample size loss, each group needed 84 participants, totaling 168 participants required for the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e2.12 Statistical Analysis\u003c/h2\u003e \u003cp\u003eThe data will be analyzed by R software (R Foundation), version 4.2.1. An independent statistician who does not know the group assignments will run the statistical analysis. Continuous variables will be described as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD with a 95% CI in a normal distribution and median (range) in abnormal distribution, while categorical variables will be represented by numbers (percentages). All statistical tests will be two-sided, and a p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 will be considered statistically significant.\u003c/p\u003e \u003cp\u003eAll analyses will be performed according to intention-to-treat (ITT) protocol. Participants who finish the baseline assessment of primary outcome and receive at least one session of either EA or sEA will be included in the ITT analysis. The missing values will be imputed by multiple imputations. Per-protocol population analysis will be also performed, for participants who have finished at least 80% of the treatment protocol after randomization.\u003c/p\u003e \u003cp\u003eThe primary analysis used a linear regression model to test whether acupuncture improved GS more than sham acupuncture. Secondary analyses were done for other outcomes. Continuous data (SMI, SPPB, IPAQ scores, serum inflammatory factor levels; and patient subjective evaluation of efficacy) were analyzed using the same linear regression model. Categorical and count datawill be compared by the χ2 test or Fisher\u0026rsquo;s exact test.\u003c/p\u003e "},{"header":"Discussion","content":" \u003cp\u003eSarcopenia in the elderly can be classified within the categories of \"Wei Syndrome\" and \"Wei Bi\" in traditional Chinese medicine (TCM), with the affected areas being the limbs and the root cause in the organs. The Yellow Emperor\u0026rsquo;s Inner Canon records that Yangming meridians must be focused in treating Wei Syndrome. Foot Yangming meridian is related to the stomach, which is responsible for receiving, digesting, and transforming nutrients from food and water, and is closely connected with the the Spleen Meridian of Foot Taiyin, mutually influencing each other. Hand Yangming meridian is related to the large intestine, which processes waste and is responsible for \"fluids\" that nourish the organs, bones, and joints, and moisturize the whole body. If Yangming is deficient, the generation and transformation of essence and blood will be insufficient, leading to abnormalities in receiving and transforming nutrients. This results in the body's inability to receive nutrients and irrigate the surrounding areas, causing malnourishment of muscles and tendons, and the manifestation of \"Wei Syndrome\" in the limbs. Focusing on Yangming in the treatment of sarcopenia in the elderly emphasizes the importance of regulating and protecting the spleen and stomach. By stimulating the Yangming Meridian, the spleen and stomach can be regulated, helping transport the essence of food and water, replenishing qi and blood, improving the state of inadequate intake and absorption, and activating muscle function. In electroacupuncture treatment for sarcopenia in the elderly, the Zusanli acupoint on the Yangming Meridian is the fundamental and essential acupoint in the treatment.\u003c/p\u003e \u003cp\u003eThe pathogenesis of sarcopenia is complex, involving factors such as age-related anabolic hormone changes, loss of motor neurons, apoptosis of muscle satellite cells, and mitochondrial dysfunction. Among these factors, inflammation plays a crucial role in the pathophysiology of sarcopenia. Studies have shown that the inflammatory marker C-reactive protein (CRP) is negatively correlated with muscle strength and mass(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Elevated levels of high-sensitivity CRP (hs-CRP), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) are significant risk factors for sarcopenia(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). A cohort study of Chinese subjects found that high levels of inflammatory markers IL-6 and TNF-α were associated with an increased risk of sarcopenia, and logistic regression analysis showed that high levels of TNF-α (11.15 pg/ml) increased the risk of sarcopenia by 7.6 times(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Elevated serum IL-6 and TNF-α levels can not only predict the occurrence of sarcopenia but also predict adverse clinical outcomes such as disability and death(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). A meta-analysis showed that high levels of CRP, IL-6, and TNF-α were negatively correlated with grip strength, knee extension strength, and muscle mass, indicating that high levels of circulating inflammatory markers are significantly associated with lower skeletal muscle strength and mass(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). It is still unclear whether electroacupuncture can exert its clinical effects on sarcopenia treatment by modulating the levels of inflammatory mediators.\u003c/p\u003e \u003cp\u003eTherefore, this study focuses on elderly sarcopenia patients and adopts a randomized controlled trial design. In addition to exploring the clinical effects of electroacupuncture treatment for elderly sarcopenia, we aim to preliminarily investigate the potential underlying mechanisms involving and inflammatory responses. Our goal is to provide a new treatment option for elderly sarcopenia patients, break through therapeutic bottlenecks, and ultimately benefit numerous patients.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics and Dissemination\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study protocol was reviewed and approved by the Institutional Review Board of West China Hospital of Sichuan University. The participants will provide written informed consent to participate in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research will be conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHL and LZ contributed equally to this article. HL, LYL and LZ conceived the idea for this study. XZ participated in the design and drafted the manuscript. QW and YH will be responsible for recruiting subjects. CX and YJ are responsible for collecting the data. LT, BMZ and\u0026nbsp;NL contributed to the final version of the manuscript. LZ and LYL will be responsible for monitoring this study. All authors contributed to manuscript revision and have read and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is supported by the Sichuan Science and Technology Program (grant number: 2023YFS0247).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the participants in the study, including the participants, statisticians, acupuncturists, and evaluators, as well as West China Hospital of Sichuan University for their support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHaase CB, Brodersen JB, B\u0026uuml;low J. Sarcopenia: early prevention or overdiagnosis? BMJ. 2022;376:e052592.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, et al. Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment. J Am Med Dir Assoc. 2020;21(3):300\u0026ndash;e72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen X, Hou L, Zhang Y, Dong B. Analysis of the Prevalence of Sarcopenia and Its Risk Factors in the Elderly in the Chengdu Community. J Nutr Health Aging. 2021;25(5):600\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoshimura N, Muraki S, Oka H, Iidaka T, Kodama R, Kawaguchi H, et al. Is osteoporosis a predictor for future sarcopenia or vice versa? Four-year observations between the second and third ROAD study surveys. Osteoporos Int. 2017;28(1):189\u0026ndash;99.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eProkopidis K, Giannos P, Katsikas Triantafyllidis K, Kechagias KS, Mesinovic J, Witard OC, et al. Effect of vitamin D monotherapy on indices of sarcopenia in community-dwelling older adults: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2022;13(3):1642\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCorrea C, Bieger P, Perry IS, Souza GC. Testosterone Supplementation on Sarcopenia Components in Chronic Patients: A Systematic Review and Meta-Analysis. Curr Pharm Des. 2022;28(7):586\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRooks D, Roubenoff R. Development of Pharmacotherapies for the Treatment of Sarcopenia. J Frailty Aging. 2019;8(3):120\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVald\u0026eacute;s-Badilla P, Guzm\u0026aacute;n-Mu\u0026ntilde;oz E, Hernandez-Martinez J, N\u0026uacute;\u0026ntilde;ez-Espinosa C, Delgado-Floody P, Herrera-Valenzuela T, et al. Effectiveness of elastic band training and group-based dance on physical-functional performance in older women with sarcopenia: a pilot study. BMC Public Health. 2023;23(1):2113.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang H, Huang WY, Zhao Y. Efficacy of Exercise on Muscle Function and Physical Performance in Older Adults with Sarcopenia: An Updated Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2022;19(13).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVlietstra L, Hendrickx W, Waters DL. Exercise interventions in healthy older adults with sarcopenia: A systematic review and meta-analysis. Australas J Ageing. 2018;37(3):169\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen N, He X, Feng Y, Ainsworth BE, Liu Y. Effects of resistance training in healthy older people with sarcopenia: a systematic review and meta-analysis of randomized controlled trials. Eur Rev Aging Phys Act. 2021;18(1):23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRobinson SM, Reginster JY, Rizzoli R, Shaw SC, Kanis JA, Bautmans I, et al. Does nutrition play a role in the prevention and management of sarcopenia? Clin Nutr. 2018;37(4):1121\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa SF, Lv WY, Zhu QY, Li HJ, Li JJ, Shi Q, et al. [Electroacupuncture at acupoints of yangming meridians for sarcopenia: a randomized controlled trial]. Zhongguo Zhen Jiu. 2023;43(10):1114\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu ZW, Tang CL, Li XH, Yang ZX, Yang YH, Pang F, et al. [Effects of electroacupuncture on proangiogenesis process and protein turnover in a mouse model of sarcopenia]. Zhen Ci Yan Jiu. 2020;45(12):973\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou X, Xing B, He G, Lyu X, Zeng Y. The Effects of Electrical Acupuncture and Essential Amino Acid Supplementation on Sarcopenic Obesity in Male Older Adults: A Randomized Control Study. Obes Facts. 2018;11(4):327\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoares Mendes Damasceno G, Teixeira T, de Souza VC, Neiva TS, Prudente Pereira K, Teles Landim MF, et al. Acupuncture Treatment in Elderly People with Sarcopenia: Effects on the Strength and Inflammatory Mediators. J Aging Res. 2019;2019:8483576.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHida T, Imagama S, Ando K, Kobayashi K, Muramoto A, Ito K, et al. Sarcopenia and physical function are associated with inflammation and arteriosclerosis in community-dwelling people: The Yakumo study. Mod Rheumatol. 2018;28(2):345\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRong YD, Bian AL, Hu HY, Ma Y, Zhou XZ. Study on relationship between elderly sarcopenia and inflammatory cytokine IL-6, anti-inflammatory cytokine IL-10. BMC Geriatr. 2018;18(1):308.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi CW, Yu K, Shyh-Chang N, Li GX, Jiang LJ, Yu SL, et al. Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention. J Cachexia Sarcopenia Muscle. 2019;10(3):586\u0026ndash;600.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrosicki GJ, Barrett BB, Englund DA, Liu C, Travison TG, Cederholm T, et al. Circulating Interleukin-6 Is Associated with Skeletal Muscle Strength, Quality, and Functional Adaptation with Exercise Training in Mobility-Limited Older Adults. J Frailty Aging. 2020;9(1):57\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTuttle CSL, Thang LAN, Maier AB. Markers of inflammation and their association with muscle strength and mass: A systematic review and meta-analysis. Ageing Res Rev. 2020;64:101185.\u003c/span\u003e\u003c/li\u003e\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":"bmc-complementary-medicine-and-therapies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcam","sideBox":"Learn more about [BMC Complementary Medicine and Therapies](https://bmccomplementmedtherapies.biomedcentral.com/)","snPcode":"","submissionUrl":"","title":"BMC Complementary Medicine and Therapies","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"electroacupuncture, sarcopenia, randomized controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-4109912/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4109912/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction: \u003c/strong\u003eSarcopenia is a disease primarily characterized by age-related loss of skeletal muscle mass, muscle strength, and/or decline in physical performance. Sarcopenia has an insidious onset which can cause functional impairment in the body and increase the risk of falls and disability in the elderly. It significantly increases the likelihood of fractures and mortality, severely impairing the quality of life and health of the elderly people. This disease poses a heavy burden on the healthcare system and society in our country, and currently, there are limited clinical intervention strategies for sarcopenia. This study aims to explore the clinical efficacy and safety of electroacupuncture in treating sarcopenia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods and Analysis:\u003c/strong\u003e In this parallel-design, randomized, sham-controlled trial, a total of 168 elderly sarcopenia patients will be randomly assigned in a 1:1 ratio to receive either electroacupuncture (EA) or sham electroacupuncture (sEA) treatment. The acupuncture points used in the study are Hegu (LI4), Shousanli (LI10), Quchi (LI11), Binao (LI14), Futu (ST32), Liangqiu (ST34), Zusanli (ST36), and Jiexi (ST41). The participants will receive EA or sEA treatment three times per week for eight weeks. The primary outcome measure is the change in grip strength (GS) of the patients after the eight-week treatment. The secondary outcome measures include the changes in grip strength at the fourth and twentieth weeks, changes in appendicular skeletal muscle mass index (ASMI), the Short Physical Performance Battery (SPPB) score, the physical activity level (PAL) assessed by the International Physical Activity Questionnaire (IPAQ), assessment of expectations regarding the efficacy of acupuncture, patient subjective evaluation of efficacy, and evaluation of blinding efficacy of acupuncture. All statistical analyses will be conducted according to the intention-to-treat principle and as per the study protocol.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics and Dissemination: \u003c/strong\u003eThis study protocol was reviewed and approved by the Institutional Review Board of West China Hospital of Sichuan University (permission number: 2023-525). The participants will provide written informed consent to participate in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration:\u003c/strong\u003e Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2300079294.\u003c/p\u003e","manuscriptTitle":"Electroacupuncture Treatment for Sarcopenia: Study Protocol for a Randomized Controlled Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-21 16:06:26","doi":"10.21203/rs.3.rs-4109912/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-26T12:51:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-30T09:14:34+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-03-18T13:35:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-18T13:24:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Complementary Medicine and Therapies","date":"2024-03-15T18:57:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-complementary-medicine-and-therapies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcam","sideBox":"Learn more about [BMC Complementary Medicine and Therapies](https://bmccomplementmedtherapies.biomedcentral.com/)","snPcode":"","submissionUrl":"","title":"BMC Complementary Medicine and Therapies","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bf8c2805-2ea2-4d3c-9f0e-ad07978e41f7","owner":[],"postedDate":"March 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-12-06T18:23:26+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-21 16:06:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4109912","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4109912","identity":"rs-4109912","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}