Objectives
The objectives are: 1) determine the efficacy of acupuncture for the treatment of insomnia disorder and 2) elucidate the neural mechanisms for the effects of acupuncture on insomnia disorder.
Hypothesis
- We hypothesize that sleep quality will be significantly improved in the group receiving acupuncture treatment versus the sham group, as assessed by both subjective (PSQI) and objective (actigraphy) measurements.
- The hyperarousal state, measured by HAS, will be decreased more in the group receiving acupuncture versus the sham group.
- Based on fMRI examination, functional connectivity and ReHo, in the emotion-related areas, will be altered in the group receiving acupuncture versus the sham group.
Setting
The trial site will be the Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China. Sixty patients with insomnia disorder will be assigned to either a real acupuncture group or a sham group, using a digital randomization table in a 1:1 ratio.
Trial design
This study will be conducted as a single-center, prospective parallel-group, patient-assessor-blinded, randomized controlled trial (RCT). The trial will be conducted in accordance with the CONSORT (Consolidated Standards of Reporting Trials) [18] and STRICTA (Standards for Reporting Interventions in Clinical Trials of Acupuncture) principles [19], to fulfill adequate reporting standards for RCTs. Sixty patients, with insomnia disorder, will be assigned to either a real acupuncture group or a sham acupuncture group, using a digital randomization table in a 1:1 ratio. Participants will keep a sleep diary at baseline, during the 4th week of treatment, and during the 8th week of follow-up period. Both the neuropsychological measurements and fMRI scans will be performed at baseline, after completion of the acupuncture treatments, and at the conclusion of the follow-up period. Thirty age- and sex-matched healthy good sleepers will be recruited as controls for the fMRI data analysis. All outcome measures will be performed once for the healthy control patients. (Fig. 1)
Participants and recruitment
Posted notices in the hospital and recruitment information on the website of the Beijing Hospital of Traditional Chinese Medicine will be used to recruit study participants.
Participants will be informed about the benefits, as well as possible risks, of participation in the study, including poor clinical outcome and adverse events associated with acupuncture therapy. Completion of consent forms will be compulsory before trial participation and randomization. A neurologist will determine the PSQI, HAS, HAMD, HAMA scores to decide whether the participants meet the inclusion criteria. Patients who satisfy the inclusion criteria will be randomized (1:1) into either a real acupuncture group or a sham acupuncture group. All participants will complete the baseline rs-fMRI, a 3-day actigraphy test, and the 1-week sleep diary. Participants will receive acupuncture treatment for 4 weeks. In addition, thirty age- and sex-matched Healthy good sleepers will be recruited as healthy controls for the fMRI data analysis. All personal information about the participants will be maintained confidentially by the research investigators and used for research purposes only.
Inclusion criteria
Compliance with the criteria listed below will be required for participation in the study.
- Age between 20 and 60 years.
- Meet the diagnostic criteria for insomnia disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V).
- A PSQI score >8 points; HAMD score <7; HAMA score <14; and HAS score >32.
- Signed informed consent form specific for this trial.
- Have not received medications for anxiety, depression, or insomnia within 1 month prior to enrollment in the study.
Exclusion criteria
Patients will be excluded from enrollment in the trial if they meet one or more of the following:
- Diagnosis of anxiety, depression, or schizophrenia.
- Diagnosis of severe medical disorders, including cardiac, cerebral, renal, hepatic, or metabolic diseases, or benign prostatic hyperplasia.
- Diagnosis of other sleep disorders, such as sleep apnea and restless leg syndrome
- Women who are pregnant or breastfeeding.
- Difficulty completing the inspection and treatment.
- Contraindication for MRI including claustrophobia. Abnormal signal or obvious asymmetrical head structure by MRI.
- Acupuncture therapy for insomnia treatment in the past month.
- Addiction to drugs or alcohol.
Inclusion criteria for healthy good sleepers
- No complaints of sleep quality and quantity.
- Patients between 20 and 60 years of age.
- Signed informed consent form specific for this trial.
- Have not received medications for anxiety, depression, or insomnia within 1 month prior to enrollment in the study.
Sample size
This pilot study aims to determine the efficacy and central mechanism by which acupuncture affects insomnia disorder. Based on our previous pilot study [20], the PSQI score significantly decreased by 4.43 ± 3.60 in the group treated with acupuncture compared to 1.30 ± 2.58 in the control group. Based on a power analysis, 26 patients per group were required to detect a significant difference (power = 0.9, 𝛼 = 0.05, two-sided). Thus, we plan on recruiting 30 patients per group, to compensate for a 15% drop out rate. There is no known sample size calculation for fMRI research [21]. However, for exploratory and pilot studies, 10 to 30 patients are adequate to test the null hypothesis [22].
Ethics
Protocol approval was obtained by the Medical Ethical Committee of Beijing Hospital of Traditional Chinese Medicine on 12 March 2018 (2018BL–002–02). Written informed consent will be attained from each participant. This trial is funded by the National Natural Science Foundation of China (81774391, 81871507).
Randomization, allocation concealment, and blinding
After meeting the eligibility requirements, participants will be randomly assigned (1:1 ratio) to the real or the sham acupuncture group. The random allocation sequence will be generated by an independent statistician using Statistical Analysis Software (version 9.3, SAS Institute Inc., Cary, NC, USA). The randomization list will be closed in computer-made opaque envelopes with sequence numbers printed on the outside of the envelopes. After the patient has been screened, determined to be eligible, and has given informed consent, the envelopes will be opened by the researchers.
The acupuncturists cannot be blinded, and, therefore, will be excluded from assessments and data processing. In the trial, the participants, data analysts, and outcome assessors will be blinded. Assessors will not perform data analysis.
In addition, sterile steel needles of the same size and number for each treatment session will be used in both groups. Participants will be required to write down if they have received real acupuncture at the final treatment. The answer ‘Y’ or ‘N’ will be assessed to determine the confidence in the treatment.