Acupuncture for Insomnia in Breast Cancer Patients Undergoing Chemotherapy

Study Overview
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Brief Summary
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The proposed study is a randomized, parallel-group, placebo-controlled, subject- and assessor-blind trial. It is designed according to CONSORT and STRICTA recommendations. The 138 subjects will be randomly assigned to one of the two arms using block randomization in a 1:1 ratio: (I) acupuncture treatment, and (II) sham treatment. In groups (I) and (II), acupuncture or sham acupuncture treatment will be given twice a week for 6 weeks (12 sessions). A maintenance tapering treatment schedule will then be applied once per month for 3 months (3 sessions). The primary outcome will be improvement in sleep quality as measured by the change of ISI after 6 weeks of treatment. Secondary outcome assessment tools will include PSQI, HADS, BPI, BFI, FACT-B, sleep diaries, drug diaries, blinding success questionnaire and reports of adverse events. The subjects will be scheduled for on-site follow-up assessments at 3 and 6 months after the last treatment. An intention to treat (ITT) approach will be used for data analysis.

Detailed Description
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Insomnia is a frequent and disturbing symptom among cancer patients. Studies have found that cancer treatments, particularly chemotherapy, are a major cause of cancer-related insomnia. However, insomnia is under-treated in most breast cancer patients because effective, safe evidence-based treatments are lacking. Acupuncture has been used for thousands of years to treat various diseases, including insomnia. Our previous research demonstrated the efficacy and safety of acupuncture as a treatment for insomnia. However, the effect of acupuncture on insomnia in breast cancer patients who undergo chemotherapy has been rarely studied. We propose this randomized controlled trial to examine the feasibility, effect and safety of acupuncture as a treatment for insomnia in breast cancer patients who undergo chemotherapy. Hypothesis: We hypothesize that acupuncture is a feasible, effective and safe method for the alleviation of insomnia symptoms in breast cancer patients undergoing chemotherapy as compared with a sham control. Primary Aim: To determine whether the insomnia condition in the acupuncture group is significantly improved when compared to the sham control group, as measured by the ISI after 6 weeks of treatment. Secondary Aims: 1) To determine whether other sleep-related parameters in the acupuncture group improve more than those of the control group, as measured at different time points by Actiwatch, sleep diary, Pittsburgh Sleep Quality Index (PSQI), Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B), Hospital Anxiety and Depression Scale (HADS), Brief Fatigue Inventory (BFI) and Brief Pain Inventory (BPI). 2) To assess by adverse event (AE) analysis whether acupuncture is safe for treatment of insomnia in breast cancer patients undergoing chemotherapy.

Official Title
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The Effect of Acupuncture for Insomnia in Breast Cancer Patients Undergoing Chemotherapy: A Randomized, Sham-Controlled Trial

Conditions
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Insomnia, Secondary, Breast Cancer Female, Chemotherapy

Intervention / Treatment
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* Procedure: Electroacupuncture (EA) and Auricular Acupressure (AA)
* Procedure: Sham Electroacupuncture (SE) and Sham Auricular Acupressure (SA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients between 18 and 75 years of age. Diagnosis of stage (American Joint Committee on Cancer (AJCC) TNM) I-IV breast cancer. Currently receiving chemotherapy, or have completed chemotherapy no more than 6 months. Insomnia onset after the diagnosis of breast cancer. Insomnia occurs at least 3 nights per week, and presents for at least 1 month, with fulfilment of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for brief insomnia disorder Insomnia severity as defined by an ISI score of no less than 10 in the past 2 weeks. Expected survival time of more than 6 months. Ability to understand the nature of the study and willingness to give informed consent. Ability to provide responses during outcome measurement. Exclusion Criteria: Other sleep disorder (e.g., obstructive sleep apnoea). Shift work or irregular sleep pattern. Severe visual, hearing or language defects. Severe hematological dysfunction (platelet count <60,000/μL, haemoglobin <8 g/dL or absolute neutrophil count <1000/μL). History of acupuncture use in the previous 3 months. Participation in other clinical trials with intervention within 3 months of the beginning of the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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: True acupuncture group<br>12 sessions of acupuncture treatment (EA+AA) will be given twice a week for 6 weeks after randomization, followed by once a month for 3 months, for a total of 15 sessions of treatments. | Procedure: Electroacupuncture (EA) and Auricular Acupressure (AA)<br>* EA: Ten points will be used, including GV24 (Shenting), GV20 (Baihui), EX-HN1 (Sishenchong), PC6 (Neiguan), CV12 (Zhongwan), CV4 (Guanyuan), ST25 (Tianshu), ST36 (Zusanli), SP6 (Sanyinjiao), KI3 (Taixi). AA: Vaccaria seeds will be embedded by acupuncturists on three auricular points (Shenmen, Sympathetic and Heart) and maintained between EA treatments.<br>|
| Placebo Comparator: Sham acupuncture group<br>12 sessions of sham acupuncture treatment (SE+SA) will be given twice a week for 6 weeks after randomization, followed by once a month for 3 months, for a total of 15 sessions of treatments. | Procedure: Sham Electroacupuncture (SE) and Sham Auricular Acupressure (SA)<br>* SE: The sham acupuncture treatment procedure, including the acupoint selection principle, sterilization procedure and treatment schedule, will be the same as in the acupuncture treatment group, except that sham points 1 to 2 cm exterior and inferior to the real points will be used, and no needle penetration or electric stimulation will be performed. SA: Three sham auricular points in the helix region (HX7, HX8, HX9) will be selected. Instead of Vaccaria seeds, soft Junci Medulla (1 to 2 mm in length, dyed black) will be used to mimic real AA with no pressure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insomnia Severity Index (ISI) | The primary outcome will be the change of ISI score between the baseline and the end of the 6-week treatment. The ISI is a seven-item questionnaire devised to diagnose and assess the severity of insomnia. | Baseline, 3 week, 6 week, 10 week, 14 week, 18 week, 30 week, 42 week. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actiwatch | The subjects will wear Actiwatch for 1 week at baseline period and the end of 6-week treatment. | Baseline, 6 week. | 
| Sleep diary | Subjects will be given daily sleep diary for 1 week at baseline period and the end of 6-week treatment. | Baseline, 6 week. | 
| Pittsburgh Sleep Quality Index (PSQI) | The PSQI is a reliable and valid self-reported questionnaire that assesses sleep quality over 1 month. | Baseline, 3 week, 6 week, 10 week, 14 week, 18 week, 30 week, 42 week. | 
| Hospital Anxiety and Depression Scale (HADS) | The HADS, a 14-item self-rated questionnaire, evaluates the severity of depressive and anxiety symptoms. | Baseline, 3 week, 6 week, 10 week, 14 week, 18 week, 30 week, 42 week. | 
| Brief Pain Inventory-Short Form (BPI-SF) | The BFI is a brief screening tool designed to assess the severity and impact of cancer-related fatigue on daily functioning. | Baseline, 3 week, 6 week, 10 week, 14 week, 18 week, 30 week, 42 week. | 
| Brief Fatigue Inventory (BPI) | The BPI is a self-administered questionnaire designed to assess cancer pain. | Baseline, 3 week, 6 week, 10 week, 14 week, 18 week, 30 week, 42 week. | 
| Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) | The FACT-B is a patient-reported outcome measure used to assess health-related quality of life in breast cancer patients. | Baseline, 3 week, 6 week, 10 week, 14 week, 18 week, 30 week, 42 week. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acupuncture, Insomnia, Breast cancer, Chemotherapy