Acupuncture Plus Lifestyle Management for Insulin Resistance in Women With Polycystic Ovary Syndrome: Protocol for a Phase I Single-Arm Trial and a Planned Phase II Randomized Controlled Trial (Preprint)

BACKGROUND Insulin resistance (IR) is a central pathogenic feature of polycystic ovary syndrome (PCOS). Acupuncture may improve metabolic and reproductive dysfunction, but robust evidence regarding its effectiveness and safety for PCOS-related IR remains insufficient. A staged clinical development program is therefore proposed, beginning with an exploratory phase I study before progression to a confirmatory phase II trial. OBJECTIVE This study aims to evaluate safety, tolerability, and feasibility as the phase I primary outcomes; to explore the preliminary change in IR, assessed by homeostatic model assessment of insulin resistance (HOMA-IR) from baseline to week 12, as an exploratory efficacy outcome; and to use the phase I findings to determine progression criteria, refine the phase II design, and calculate the phase II sample size. METHODS Phase I is a prospective, single-center, open-label, single-arm exploratory clinical trial that will recruit participants until 20 women with PCOS and IR have completed the 12-week intervention and the week 12 HOMA-IR assessment. Participants who withdraw before completing the week 12 assessment will be replaced to ensure 20 evaluable completers, while their available safety and feasibility data will be retained. All participants will receive active acupuncture for 30 minutes 3 times per week for 12 weeks (a planned maximum of 36 sessions) together with standardized lifestyle management, followed by a 12-week follow-up. Assessments will follow the screening, baseline, week 12, and week 24 schedule. The phase I primary outcomes are safety, tolerability, and feasibility. The exploratory efficacy outcome is the change in HOMA-IR from baseline to week 12 among the 20 evaluable completers. These complete HOMA-IR data will provide the effect estimate and variance used to calculate the phase II sample size. Phase II will be a prospective, multicenter, parallel, 1:1 randomized sham-controlled trial comparing active acupuncture plus lifestyle management with sham acupuncture plus lifestyle management and will use the same participant eligibility criteria as phase I. RESULTS The two-stage clinical program is registered at ClinicalTrials.gov (NCT07806656) and has ethics approval from Peking University Third Hospital, China (PKU3-IRB-M20260279). Protocol version 3.0 is dated August 10, 2026. As of October 25, 2026, recruitment had not begun. Recruitment is expected to be completed by December 2027, and study results are expected to be published by December 2028. Phase II recruitment will begin after phase I review and finalization of its protocol and sample size. CONCLUSIONS The staged design will generate initial safety and feasibility findings and complete baseline-to-week 12 HOMA-IR data from 20 evaluable participants before a larger randomized trial is undertaken. These data will provide an empirical basis for the final phase II design and sample size. CLINICALTRIAL ClinicalTrials.gov NCT07806656; https://clinicaltrials.gov/study/NCT07806656 Keywords