Efficacy of electro-acupuncture versus sham acupuncture for diabetic peripheral neuropathy: study protocol for a three-armed randomised controlled trial.

INTRODUCTION: Specific treatment for diabetic peripheral neuropathy (DPN) is still lacking, and acupuncture may relieve the symptoms. We intend to investigate the efficacy and safety of electro-acupuncture (EA) in alleviating symptoms associated with DPN in diabetes. METHODS AND ANALYSIS: This multicentre, three-armed, participant- and assessor-blind, randomised, sham-controlled trial will recruit 240 eligible participants from four hospitals in China and will randomly assign (1:1:1) them to EA, sham acupuncture (SA) or usual care (UC) group. Participants in the EA and SA groups willl receive either 24-session EA or SA treatment over 8 weeks, followed by an 8-week follow-up period, while participants in the UC group will be followed up for 16 weeks. The primary outcome of this trial is the change in DPN symptoms from baseline to week 8, as rated by using the Total Symptom Score. The scale assesses four symptoms: pain, burning, paraesthesia and numbness, by evaluating the frequency and severity of each. All results will be analysed with the intention-to-treat population. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of the Beijing University of Chinese Medicine (Identifier: 2022BZYLL0509). Every participant will be informed of detailed information about the study before signing informed consent. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2200061408.

Placebo response to sham electroacupuncture in patients with chronic functional constipation: A secondary analysis.

BACKGROUND: Chronic severe functional constipation is a common disease that requires novel and effective treatment strategies. Acupuncture might constitute a promising therapeutic approach for chronic constipation, but it reportedly engenders an enhanced placebo response. Herein, we aimed to determine the magnitude of the placebo responses to electroacupuncture for constipation and identify its influencing factors. METHODS: In this secondary analysis of a multicenter randomized trial, patients were randomized to a sham electroacupuncture group, which was administered for 8 weeks in 24 sessions of superficial needling at nonacupoints. The placebo response rates were assessed using three responder criteria: ≥3 complete spontaneous bowel movements per week (CSBMs/week), overall CSBM, and sustained CSBM. Logistic regression with backward selection method was employed to identify the potential factors that affected the placebo response. KEY RESULTS: Overall, 539 patients were included in the study. The placebo response rate was 10.58%, 9.46%, and 9.09% according to the three aforementioned criteria, respectively. Those who exhibited more CSBMs/week at baseline were more likely to respond to sham electroacupuncture. Among patients with more than one CSBM per week at baseline, the response rates for achieving the criteria of ≥3 CSBMs per week, overall CSBM, and sustained CSBM were 25.40%, 30.16%, and 22.22%. CONCLUSIONS AND INFERENCE: Electroacupuncture did not demonstrate a large placebo response in functional constipation treatment. The number of CSBMs at baseline may be a moderator of the placebo response to sham electroacupuncture. Thus, superficial needling sham acupuncture may be considered an ideal sham control for clinical trials of chronic constipation.

Placebo response in sham-acupuncture-controlled trials for migraine: A systematic review and meta-analysis.

AIM: To understand the placebo response of acupuncture and its effect on migraine and optimize the design of future acupuncture clinical trials on migraine treatment. METHODS: Randomized controlled trials with sham acupuncture as a control in migraine treatment were searched in four English databases from inception to September 1, 2022. The primary outcome was placebo response rate. Secondary outcomes were migraine symptoms, emotional condition, and quality of life. Factors associated with placebo response were also explored. Results were combined using risk difference (RD) or standardized mean difference (SMD) and 95% confidence interval (CI) with a random effects model. RESULTS: The final analysis included 21 studies involving 1177 patients. The pooled response rate of sham acupuncture was 0.34 (RD, 95% CI 0.23-0.45, I2 89.8%). The results (SMD [95% CI]) showed significant improvements in migraine symptoms (pain intensity -0.56 [-0.73 to -0.38], and episode conditions -0.55 [-0.75 to -0.35]); emotional condition (anxiety scale -0.49 [-0.90 to -0.08] and depression scale -0.21 [-0.40 to -0.03]); and quality of life on the Migraine-Specific Quality-of-Life Questionnaire (restrictive 0.78 [0.61-0.95]; preventive 0.52 [0.35-0.68]; and emotional 0.45 [0.28-0.62]) and on the Medical Outcomes Study Short-Form (physical 0.48 [0.34-0.62] and mental 0.21 [0.02-0.41]). Only acupuncture treatment frequency had a significant impact on the placebo response rate (RD 0.49 vs. 0.14; p = 0.00). CONCLUSIONS: The effect sizes for placebo response of sham acupuncture varied across migraine treatment trials. Further studies should routinely consider adjusting for a more complete set of treatment factors.

Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis.

BACKGROUND: The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear. OBJECTIVE: This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects. SEARCH STRATEGY: PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022. INCLUSION CRITERIA: Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included. DATA EXTRACTION AND ANALYSIS: Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response. RESULTS: Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response. CONCLUSION: Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis. J Integr Med. 2023; 21(5): 455-463.

Placebo Response among Different Types of Sham Acupuncture for Low Back Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Low back pain (LBP) is a prevalent and debilitating condition that poses a significant burden on healthcare systems. Acupuncture has been proposed as a promising intervention for LBP, but the evidence supporting its specific effect is insufficient, and the use of sham acupuncture as a control in clinical trials presents challenges due to variations in sham acupuncture techniques and the magnitude of the placebo effect. OBJECTIVE: To investigate the magnitude of the placebo response of sham acupuncture in trials of acupuncture for nonspecific LBP, and to assess whether different types of sham acupuncture are associated with different responses. METHODS: Four databases including PubMed, EMBASE, MEDLINE, and the Cochrane Library were searched through April 15, 2023, and randomized controlled trials (RCTs) were included if they randomized patients with LBP to receive acupuncture or sham acupuncture intervention. The main outcomes included the placebo response in pain intensity, back-specific function and quality of life. Placebo response was defined as the change in these outcome measures from baseline to the end of treatment. Random-effects models were used to synthesize the results, standardized mean differences (SMDs, Hedges'g) were applied to estimate the effect size. RESULTS: A total of 18 RCTs with 3,321 patients were included. Sham acupuncture showed a noteworthy pooled placebo response in pain intensity in patients with LBP [SMD -1.43, 95% confidence interval (CI) -1.95 to -0.91, I2=89%]. A significant placebo response was also shown in back-specific functional status (SMD -0.49, 95% CI -0.70 to -0.29, I2=73%), but not in quality of life (SMD 0.34, 95% CI -0.20 to 0.88, I2=84%). Trials in which the sham acupuncture penetrated the skin or performed with regular needles had a significantly higher placebo response in pain intensity reduction, but other factors such as the location of sham acupuncture did not have a significant impact on the placebo response. CONCLUSIONS: Sham acupuncture is associated with a large placebo response in pain intensity among patients with LBP. Researchers should also be aware that the types of sham acupuncture applied may potentially impact the evaluation of the efficacy of acupuncture. Nonetheless, considering the nature of placebo response, the effect of other contextual factors cannot be ruled out in this study. (PROSPERO registration No. CRD42022304416).

Acupuncture combined with ondansetron for prevention of postoperative nausea and vomiting in high-risk patients undergoing laparoscopic gynaecological surgery: A randomised controlled trial.

BACKGROUND: Consensus guidelines recommend the use of multiple antiemetics as prophylaxis in patients at high risk of postoperative nausea and vomiting (PONV), but the evidence regarding combining acupuncture and antiemetics as a multimodal approach was of very low quality. OBJECTIVE: This study aimed to assess the effect of combinations of acupuncture with ondansetron versus ondansetron alone for PONV prophylaxis in women at a high risk. METHODS: This parallel, randomised controlled trial was conducted in a tertiary hospital in China. Patients who had three or four PONV risk factors on the Apfel simplified risk score, undergoing elective laparoscopic gynaecological surgery for benign pathology, were recruited. Patients in the combination group received two sessions of acupuncture treatment and 8 mg intravenous ondansetron, whereas those in the ondansetron group received ondansetron alone. The primary outcome was the incidence of PONV within 24 h postoperatively. Secondary outcomes included the incidence of postoperative nausea, postoperative vomiting, adverse events etc. RESULTS: Between January and July 2021, a total of 212 women were recruited, 91 patients in the combination group and 93 patients in the ondansetron group were included in the modified intention-to-treat analysis. In the first 24 h postoperatively, 44.0% of the patients in the combination group and 60.2% of the patients in the ondansetron group experienced nausea, vomiting, or both (difference, -16.3% [95% CI, -30.5 to -2.0]; risk ratio, 0.73 [95% CI, 0.55-0.97]; p = 0.03). However, the results of the secondary outcomes showed that compared to ondansetron alone, acupuncture together with ondansetron was only effective in reducing nausea but did not have a significant impact on vomiting. The incidence of adverse events was similar between the groups. CONCLUSION: Acupuncture combined with ondansetron as a multimodal prophylaxis approach is more effective than ondansetron alone in preventing postoperative nausea in high-risk patients.

Efficacy of acupuncture in improving symptoms and quality of life of patients with acne vulgaris: a randomized sham acupuncture-controlled trial.

OBJECTIVE: The aim of this study was to examine the effectiveness of acupuncture in treating the symptoms and quality of life (QoL) of patients with moderate or severe acne vulgaris (AV). METHODS: Participants were randomly assigned (1:1) to receive 12 treatment sessions of acupuncture or sham acupuncture over 4 weeks with 24 weeks of follow-up. The primary outcome was the change from baseline in the Skindex-16 scale total score at treatment completion. Secondary outcomes included Skindex-16 subscale score, Dermatology Life Quality Index scale total score, total lesion count and inflammatory lesion count, and visual analogue scale scores for itch and pain evaluation. RESULTS: There was no statistically significant between-group difference for the primary outcome or any secondary outcomes after 4 weeks of treatment and at 16 and 28 weeks of follow-up, except for the Skindex-16 emotions subscale at week 4 (p = 0.026). No serious adverse events occurred in either group. CONCLUSION: Acupuncture may not effectively relieve the symptoms of patients with moderate or severe AV, or improve QoL. Given the limitations of a relatively short treatment course compared to other studies and the likelihood that sham acupuncture is not inert, further studies with treatment durations of 12 weeks or longer and a waitlist (no treatment) control or Western medicine-treated control group should be considered to evaluate the effects of acupuncture on AV. TRIAL REGISTRATION NUMBER: ChiCTR-1900023649 (Chinese Clinical Trial Registry).

[Review of clinical research in acupuncture and moxibustion from 2010 to 2020 and future prospects].

The progress of Chinese clinical research on acupuncture and moxibustion in recent 10 years was reviewed and analyzed, and corresponding suggestions were put forward for the current problems. In the past 10 years, Chinese clinical research on acupuncture and moxibustion has made considerable progress, mainly in the following areas: a series of internationally recognized clinical research evidences have been published, a preliminary acupuncture clinical evaluation system has formed, sham/placebo acupuncture control is widely used internationally, acupuncture clinical research norms and standards have been initially established. However, the following issues still need to be paid attention to in follow-up research: focus on the overall layout and refinement of clinical research, further improvement of clinical evaluation system, developing relevant norms for sham/placebo acupuncture setting and reporting, strengthening data sharing and platform integration, building a smooth basic and two-way transformation clinical pathway, etc.

Effect of electroacupuncture in pre- and postmenopausal women with stress urinary incontinence: A subgroup analysis of two randomised clinical trials.

OBJECTIVE: To evaluate the effect of electroacupuncture and assess the impact of menopausal status in women with stress urinary incontinence or stress-predominant mixed urinary incontinence. METHODS: This study was conducted as a subgroup analysis of the data collected from two multicentre, randomised controlled trials conducted on 1004 women; 384 of these subjects were pre- or postmenopausal women who received the same electroacupuncture treatment for stress urinary incontinence or stress-predominant mixed urinary incontinence. The primary outcome evaluated in this study was the proportion of subjects who had at least a 50% reduction in the mean 72-hour incontinence episodes frequency from baseline and the difference between pre- and postmenopausal groups, as measured at the end of 6 weeks using the 72-hour bladder dairy. RESULTS: Among the 384 women, 132 were premenopausal and 252 were postmenopausal. Compared with the baseline, measurement at the end of 6 weeks of treatment showed at least 50% reduction in the mean 72-hour incontinence episodes frequency in 61.83% and 58.85% of the women in the premenopausal and postmenopausal groups, respectively (difference 1.06%, 95% confidence interval, -13.87 to 15.99; P = .889). No statistically significant intergroup differences were noted in the changes from baseline in the International Consultation on Incontinence Questionnaire-Short Form score and the 1-hour amount of urine leakage. Electroacupuncture-related adverse events occurred in 1.52% of the premenopausal and 1.59% of the postmenopausal women. CONCLUSION: This subgroup analysis indicated that electroacupuncture can improve the symptoms of urinary incontinence in women with stress urinary incontinence or stress-predominant mixed urinary incontinence and that menopausal status may not affect the effects of electroacupuncture in subjects.