Efficacy of EA on Depression Related Insomnia: Study Protocol for a Multicenter RCT

Study Overview
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Brief Summary
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The investigators describe a protocol for a multicenter randomized controlled trial to find out the efficacy of electroacupuncture for depression related insomnia.

Detailed Description
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Sleep difficulties are among the main symptoms presented by depressed patients, and they can profoundly impact course of illness. Acupuncture is a widely recognized therapy to treat depressive disorders and sleep disturbances in clinical practice. This multicenter randomized placebo-controlled trial is aimed to investigate the efficacy and safety of electroacupuncture, sham acupuncture and standard medical care, administrated by professional acupuncturists and psychiatrists, in depression patients with insomnia. The investigators describe a protocol for a multicenter randomized controlled trial. Two hundred seventy eligible patients in 3 different health-care centers in Shanghai will be randomly assigned to one of 3 treatment groups: EA group (electroacupuncture+standard medical care), Control A group (sham acupuncture+standard medical care) and Control B group (standard medical care). Treatment will be given 3 times per week for 8 weeks. The primary outcomes is the Pittsburgh Sleep Quality Index (PSQI). The secondary outcomes are sleep parameters recorded in the Actigraphy, Hamilton Rating Scale for Depression (HAMD) score and Self-rating Anxiety Scale (SAS) score. Daily dose of patients' antidepressant and sedative-hypnotic medication will be recorded in the dairy. All adverse effects will be assessed by the Treatment Emergent Symptom Scale (TESS). Outcomes will be evaluated at baseline, 4 weeks post-treatment and 8 weeks post-treatment, as well as at 1 month, 3 months and 6 months follow-up. The findings from this trial will help further about the efficacy and safety of acupuncture for depression related insomnia, as well as determine the differences between electroacupuncture, sham acupuncture and standard medical care for treating insomnia and depression.

Official Title
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Efficacy and Safety of Electroacupuncture on Treating Depression Related Insomnia: Study Protocol for a Multicenter Randomized Controlled Trial

Conditions
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Insomnia Due to Mental Disorder

Intervention / Treatment
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* Device: Electroacupuncture(EA)
* Device: Placebo acupuncture
* Other: Standard care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants aged 18-70; Participants who meet the diagnostic criteria of depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV); Participants whose HAMD score is 20-35; Participants who have complaint about insomnia at the first visit to the doctor; Participants whose PSQI score is more than 7; Participants who voluntarily agree with the investigation and sign a written informed consent form for the clinical trial. Exclusion Criteria: Participants with secondary depressive disorders caused by organic diseases, medicine, or psychotic disorders including schizophrenia, etc; Participants who are in the depressive episode of bipolar disorder, or suffering from dysthymia, reactive depression and depressive syndrome caused by other diseases; Participants with alcohol abuse or drug dependence; Participants who refuse to wear the Actigraphy during the trial; Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Electroacupuncture group<br>electroacupuncture+standard care | Device: Electroacupuncture(EA)<br>* Participants in EA group will receive electroacupuncture treatment. Acupuncture will be applied at Baihui (GV20), Shenting (GV24), Yintang (GV29), bilateral Anmian (EX-HN22), Shenmen (HT7), SanYinjiao (SP6) and Neiguan (PC6). After needle insertion, rotating or lifting-thrusting manipulation will be applied for Deqi sensation. The EA apparatus (CMNS6-1, Jianjian Medical Device CO., LTD, China) will be connected to the needles at GV20 and GV29 for 30 minutes and deliver a continuous wave. The frequency will be set at about 30 Hz and the amplitude will be less than 20V. Participants can regularly take the antidepressants or sedative-hypnotics as before during the intervention. Besides, the investigators will strengthen health education about insomnia and depression for the patients.<br>|
| Placebo Comparator: Control A group<br>placebo acupuncture+standard care | Device: Placebo acupuncture<br>* Participants in the control A group will receive placebo acupuncture treatment with streitberger needles at the same acupoints as the electroacupuncture group. When the tip of the blunt needles touches to the skin, the patient will get a pricking sensation but there is no real needle inserted into the skin. The electroacupuncture apparatus will be set beside the patients, with no connection to the needles. Inform the patients when removing the needles after 30 minutes. Use the dry cotton ball to press the acupoints so that patients can feel the withdrawal of the 'needles'. Same health education and regular administration of antidepressants or sedative-hypnotics will be given to the participants during the intervention.<br>|
| Other: Control B group<br>standard care | Other: Standard care<br>* Participants in the control B group will keep their standard medical care for the first 8 weeks. Participants will take their regular antidepressants and the sedative-hypnotics during the whole intervention period. Same health education will be conducted as well for the participants. And after waiting for two months, these patients will be treated with the same electroacupuncture treatment as the EA group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pittsburgh Sleep Quality Index (PSQI) | The Pittsburgh Sleep Quality Index (PSQI) is a widely-used questionnaire to assess one's sleep disorders over one month. It is comprised of 19 self-rated items and 5 other-rated items. The scores include the following indicators: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of medication, and daytime dysfunction. Each indicator is rated from 0 to 3. The accumulated scores of the seven indicators constitute the total score of PSQI (0-21). The higher score indicates the worse sleep quality and severer sleep disorders. The investigators set the PSQI score at 8th week post-treatment as the primary outcome, compared with PSQI scores at other time points, to evaluate the effectiveness of acupuncture for depression related insomnia. | 8 week post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of PSQI scores from baseline to 6 month follow-up | As is mentioned above, PSQI is a widely-used questionnaire to assess one's sleep disorders over one month. In order to assess the effects of acupuncture on patients' sleep quality during the intervention period, and to assess the durative effects of acupuncture after the intervention ends, the investigators set the changes of PSQI scores between baseline to 6 month follow-up as the secondary outcome. | baseline, 4 week post-treatment, 8 week post-treatment, 1 month,3 month, 6 month follow-up | 
| Actigraphy | Actigraphy (wActiSleep-BT. LLC, Pensacola, USA), which is worn on the patient's wrist, can monitor the quality of sleep, such as sleep onset, sleep latency, total sleep time, sleep awakenings during the night, duration of sleep, and sleep efficiency. The software ActiLife6 (Version 6.8.1, ActiGraph, LLC) will be used to analyze every participant's sleep condition recorded in the actigraphy. | baseline, 4 week post-treatment, 8 week post-treatment | 
| Hamilton Rating Scale for Depression (HAMD) | The Hamilton Rating Scale for Depression (HAMD), an observer-rating questionnaire with 17 items to describe the severity of cognitive and bodily symptoms of depressive disorders. Each item is rated in 3- or 5-point scales. The higher total score indicates the severer depression. | baseline, 4 week post-treatment, 8 week post-treatment, 1 month, 3 month, 6 month follow-up | 
| Self-rating Anxiety Scale (SAS) | The Self-rating Anxiety Scale (SAS) is primarily used as a measure of somatic symptoms associated with anxiety. In using the scale, the participant will be asked to rate each item from 0-3 points according to how it applies to him or her within the past week. The standard score is the sum of the integer part of 1.25 times the raw score of the 20 items. A standard score of more than 50 points means the subject has anxious symptoms. A higher score indicates a more serious case of anxiety. | baseline, 4 week, 8 week post-treatment | 
| Dose dairy | The dose dairy is a notebook where participants will be required to record their daily dose of antidepressants or sedative-hypnotics from baseline to 6 months follow-up, as well as the dosage time. | baseline, 4 week, 8 week post-treatment, 1 month, 3 month, 6 month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acupuncture, insomnia, depression, antidepressants