Study design

This is a parallel randomised pilot trial designed to evaluate the effectiveness of AA in treating IR for women with PCOS and safety during treatment. Sixty participants diagnosed with PCOS will be recruited from First Affiliated Hospital, Heilongjiang University of Chinese Medicine. The study period is 3 months. A flowchart of the study is depicted in figure 1. The schedule of trial enrolment, interventions and assessments is provided in table 1. This protocol was written following the Standard Protocol Items: Recommendations for Interventional Trials checklist (see online additional file 1) and Standards for Reporting Interventions in Clinical Trials of Acupuncture: extending the Consolidated Standards of Reporting Trials statement.

• Download figure
• Open in new tab
• Download powerpoint

Figure 1

Study design flowchart. AA, auricular points acupressure. 

Inclusion criteria

1. Women aged between 15 and 40 years.

2. Diagnosis of PCOS according to the modified Rotterdam criteria.

3. 2 years after menarche.

4. BMI ≥23 kg/m².28

5. IR is defined by the homeostatic model assessment (HOMA-IR: (fasting insulin (μU/mL)×fasting glucose (mmol/L))/22.5). A value ≥2.14 will be considered to be indicative of IR.29

6. With no desire for children within 3 months.

PCOS is defined by the modified Rotterdam criteria: oligomenorrhea or amenorrhea, together with the presence of ≥12 antral follicles (≤9 mm) and/or ovarian volume >10 mL on transvaginal scanning, and/or clinical/biochemical hyperandrogenism. Oligomenorrhea is defined as an intermenstrual interval >35 days and <8 menstrual bleedings in the past year. Amenorrhea is defined as an intermenstrual interval >90 days. Clinical hyperandrogenism in China Mainland is defined as a Ferriman-Gallwey (FG) score ≥5.30

Exclusion criteria

1. Administration of other medications known to affect reproductive function or metabolism within the past 3 months, including oral contraceptives, gonadotropin-releasing hormone agonists and antagonists, antiandrogens, gonadotropins, antiobesity drugs, Chinese herbal medicines, antidiabetic drugs such as metformin and thiazolidinediones, somatostatin, diazoxide and calcium channel blockers.

2. Patients with other endocrine disorders including 21-hydroxylase deficiency, hyperprolactinemia, uncorrected thyroid disease, suspected Cushing’s syndrome.

3. Patients with known severe organ dysfunction or mental illness.

Interventions

Eligible patients will be randomised into one of the two arms: AA group and sham AA group. In both groups, magnetic beads (Hengshui Fengfan Medical Devices Co.) were taped to the auricular acupressure points, by the same senior acupuncture specialist who has a license to practice acupuncture and has been trained to practice AA.

Based on literature and expert experience, participants in the treatment group (AA group) will receive AA on the following seven acupoints: CO10 (Shen), CO12 (Gan), CO13 (Pi), CO18 (Nei fen mi), AT4 (Pi zhixia), TF2 (Nei sheng zhi qi) and TG2 (Xia ping)15–17; participants in the control group (sham AA group) will receive AA on the following three acupoints: LO5 (Yan), LO7 (Bian tao ti) and SF3 (Zhou) (figure 2). Sham acupoints were chosen because they will have no therapeutic effects in treating PCOS or PCOS-related conditions.31 The auricular points’ names and locations follow the ‘Nomenclature and location of auricular points’ (GB/T 13 734–2008, http://www.gb688.cn/bzgk/gb/newGbInfo?hcno=D6A125ED4011A9A625F8A3ACE425EE09) published by the Standardization Administration of People’s Republic of China.

• Download figure
• Open in new tab
• Download powerpoint

Figure 2

Locations of auricular acupoints applied in AA group (red circles) and sham AA group (green circles). AA, auricular points acupressure.

The subjects were asked to massage the auricular points with their hands four times per day, which are 30 min before three meals and sleep. Each time lasts at least 5 min; the subjects should feel sourness and heat of the ear as the response sought. The magnetic beads will be left in situ but replaced by the same acupuncture specialist with new ones once every week in the other ear. Adherence to massage over the magnetic beads was tracked via self-report logs, which was obtained at the weekly frequency during AA/sham AA treatment.

Patient and public involvement

The present trial was developed by investigators and acupuncturists based on previous clinical experience and literature. Patients were not involved in the design of the study. The outcomes were commonly used assessments of PCOS in clinical practice. The cost of interventions and outcome measurements were mostly covered by the study funding so it was not thought to be a significant burden and were in line with patient preferences. Study participants will receive a summary of her own study data and the study results once they have been published.

Outcome measures

Sample size calculation

Most methodological papers that focus on recommendations about sample size requirements for pilot trials assume that the main aim of such a trial is to estimate a quantitative measure such as the variance (or SD) of an effect size to inform the sample size calculation for a future definitive RCT. Methods focus on the precision with which such estimates can be obtained. Whitehead et al suggest that the size of a pilot trial should be related to the size of the future definitive RCT. For such a trial designed with 90% power and two-sided 5% significance, they recommend pilot trial sample sizes for each treatment arm of 75, 25, 15 and 10 for standardised effect sizes that are extra small (0.1), small (0.2), medium (0.5) or large (0.8), respectively.35 The present study is designed with 90% power and two-sided 5% significance, and sample size for each treatment arm is set to 25 subjects with the allocated ratio of 1:1. With an estimated 20% drop out rate, the recruitment plan was 30 subjects per group.

Randomisation and allocation concealment

After the baseline evaluation, 60 subjects were allocated randomly into one of the two groups in a ratio of 1:1. The identification code and random number, which were unique for each subject, were generated using SAS V.9.4 by an independent agency (TCM Translational Medicine Research Centre, First Affiliated Hospital, Heilongjiang University of Chinese Medicine). Personnel involved in the sequence generation or allocation concealment steps were not involved in the implementation step. These assignments were put into sequentially numbered, sealed, opaque envelopes. After the investigator had obtained the patient’s consent, he/she would contact the above-mentioned agency, and the agency would hand out the envelope sequentially to the investigator. Subject’s name and other details were written on the envelope by the investigator and the enveloped kept sealed until it was passed onto the acupuncturist. The envelopes were only be opened by the acupuncturist after the subject had completed baseline clinical assessments and the envelopes will be stored in a locker with no access to other personnel involved in the trial.

Blinding

Patients, investigators, outcome assessors and people responsible for the statistical analysis were blinded to the randomisation status. The acupuncturists were instructed not to exchange or reveal assignment information to other investigators or participants after he/she got randomisation status. Participants were arranged in different time schedule to avoid met with each other and information exchange. The assignment information will not be revealed until the end of the study, unless there is a serious adverse event (SAE).

Data collection and management

Study-related information such as the participant’s identity, the data collected relating to the study and medical records will remain confidential. Case report forms (CRFs) will be completed on paper forms. Data will then be entered and stored in a password protected electronic database. Original paper copies of CRFs and all study data will be stored in a locker with access to the involved researchers only.

Data analyses

Based on intention-to-treat principle, all participants randomised were involved in the statistical analysis. Continuous variables will be described as means with SD. We will compare the mean changes of variables from baseline to end of intervention using analysis of covariance models that include baseline measurement as covariates. We will compare the difference of variables from baseline to the end of intervention by paired T-test or Wilcoxon rank test. Categorical variables will be presented as frequency and we will examine their differences by χ² test or Fisher’s exact test. P<0.05 will be considered statistically significant. All analysis will be performed by SAS V.9.4.

Safety

All adverse events reported during the study period will be documented in CRFs.

SAE will be informed to the principal investigator within 24 hours. All SAEs must be reported on the adverse event page of the CRF. The principal investigator is responsible for the management of safety reporting according to local guidelines.

Trial status

The recruitment phase began in July 2018. Twenty-eight patients have been recruited till now. The estimated end date for this study is in September 2019. Protocol V.1.0, 08/07/2015.