Efficacy of Acupuncture Treatment for Breast Cancer-associated Insomnia

Study Overview
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Brief Summary
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Through a scientific and standardized multicenter, randomized, and controlled study method, the investigators evaluated the clinical efficacy and safety of acupuncture in the treatment of breast cancer-related insomnia, with a view to providing a reliable theoretical basis for the treatment of breast cancer-related insomnia with acupuncture.

Detailed Description
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Insomnia associated with breast cancer is one of the most common symptoms among breast cancer patients, which seriously affects the life quality of breast cancer patients. Therefore, how to better improve their life quality and insomnia symptoms is of important clinical significance. Previous studies have shown that acupuncture may be beneficial for improving sleep disorders in cancer patients. However, the available clinical evidence is mixed, and clinical studies on acupuncture for breast cancer-associated insomnia lack well-designed, high-quality clinical evidence. The purpose of this study was to evaluate the clinical efficacy and safety of acupuncture for breast cancer-associated insomnia.

Official Title
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Acupuncture for Breast Cancer-related Insomnia : a Multicenter Randomized Controlled Clinical Trial

Conditions
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Breast Neoplasms, Insomnia

Intervention / Treatment
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* Device: Acupuncture
* Device: Sham acupuncture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the diagnostic criteria for breast cancer in the 2022 V2 edition of the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology and the American Joint Committee on Cancer (AJCC) Cancer Staging Manual (8th edition) for breast cancer staging criteria meet the diagnostic criteria for breast cancer with TNM stage I to III; meet the diagnostic criteria for insomnia within the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and insomnia related to the cancer itself or to cancer-related treatment occurred after breast cancer diagnosis and lasted for at least 1 month. Female patients aged 18-75 years. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Sleep severity index scale (ISI) score ≥ 8. Predicted survival of ≥ 6 months. Patients had never received acupuncture treatment. No mental or intellectual abnormalities, able to understand the provisions of the scales and complete the assessment. Consent to participate in this study and sign a written informed consent. Exclusion Criteria: Combination of more serious heart, liver, kidney, and other major diseases. f applicable, indicate if participant eligibility is based on self-representation of gender identity. Patients who are pregnant or breastfeeding. Those with planned surgery during the trial. Previous history of drug abuse or addiction. Those who have taken sedative-hypnotic drugs or antipsychotic drugs 2 weeks prior to the baseline visit, or received other treatment for insomnia (e.g., cognitive behavioral therapy, etc.) 3 months prior to the baseline visit, which may affect the efficacy of the observation. Insomnia due to cancer pain with an numeric rating scale (NRS) score ≥ 4, or insomnia due to other physical diseases. Long-term night work or irregular rest and relaxation. Ulcers, abscesses, skin infections, etc. at the site of needling. Participation in other clinical medical trial studies within the last month.

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 |
| --- | --- |
| Experimental: Acupuncture group<br>Participants will be given sleep hygiene instructions. Participants will receive acupuncture treatment at Nei Guan (PC 6), Shen Men (HT 7), Shen Ting (GV 24), Yin Tang (GV 29), Zhong Wan (CV 12), San Yin Jiao (SP 6), Zhao Hai (KI 6), and Shen Mai (BL 62). Among the above acupoints, Nei Guan (PC 6), Shen Men (HT 7), San Yin Jiao (SP 6), Zhao Hai (KI 6), and Shen Mai (BL 62) are all taken from both sides. Participants will receive three treatments per week (every other day), each lasting 30 minutes, for a total of 12 sessions over the course of four weeks. The follow-up observation will be recorded on week 8 and 16. | Device: Acupuncture<br>* All acupuncture locations will be sterilized on a routine basis. As acupuncture needles are inserted, all points will be lifted, twisted, and stabbed to activate de qi, a sensation generally associated with acupuncture, including swelling, soreness, numbness, and heaviness.<br>|
| Sham Comparator: Sham acupuncture group<br>Participants will be given sleep hygiene instructions. To match the true acupuncture points, sham treatment at sham Nei Guan (PC 6), Shen Men (HT 7), Shen Ting (GV 24), Yin Tang (GV 29), Zhong Wan (CV 12), San Yin Jiao (SP 6), Zhao Hai (KI 6), and Shen Mai (BL 62) will be used. Participants will have the same needle retention time, treatment time, and follow-up time as the acupuncture group. | Device: Sham acupuncture<br>* The placebo needles selected for this study are flat-tipped needles without a tip that cannot be pierced into the skin. Also, an external patch device will hold the needles in place and these needles are visually pierced into the skin. At the end of the treatment, the acupuncturist will press the acupuncture point with a dry cotton ball to allow the patient to feel the needles being pulled out.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response rate of Insomnia Severity Index (ISI) | The percentage of people whose total Insomnia Severity Index (ISI) score decreased by ≥8 points at the end of week 4 treatment compared to the baseline score. The ISI consists of 7 items to assess the nature and symptoms of the subject's sleep disorders. Questions addressed subjects' subjective ratings of sleep quality, including the severity of symptoms, subjects' satisfaction with their sleep patterns, the impact of the degree of insomnia on daily functioning, subjects' awareness of the impact of insomnia on themselves, and their level of frustration due to their sleep disorders. The scores were 0 to 4, with a total score range from 0 to 28. Higher scores indicate more severe insomnia. ISI levels can be classified as no clinically significant insomnia (0 to 7), mild insomnia (8 to 14), moderate insomnia (15 to 21), and severe insomnia (22 to 28). | Week 4 (end of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment remission rate of Insomnia Severity Index (ISI) | The percentage of people with a total score of <8 points in total Insomnia Severity Index (ISI) score at the end of week 4, 8 and 16 of treatment compared to the baseline score. The ISI consists of 7 items to assess the nature and symptoms of the subject's sleep disorders. Questions addressed subjects' subjective ratings of sleep quality, including the severity of symptoms, subjects' satisfaction with their sleep patterns, the impact of the degree of insomnia on daily functioning, subjects' awareness of the impact of insomnia on themselves, and their level of frustration due to their sleep disorders. The scores were 0 to 4, with a total score range from 0 to 28. Higher scores indicate more severe insomnia. ISI levels can be classified as no clinically significant insomnia (0 to 7), mild insomnia (8 to 14), moderate insomnia (15 to 21), and severe insomnia (22 to 28). | Week 4 (end of treatment), week 8 (follow-up), and week 16(follow-up) | 
| Sleep Efficiency (SE) with Sleep Diary | It will be determined by sleep diary subjectively. Sleep Efficiency(SE) is the percentage of time spent asleep while in bed. It is calculated by (TST / TIB) × 100%. Sleep parameters measured by sleep diary include Sleep Onset Latency (SOL),Wake After Sleep Onset(WASO),Early morning awakening(EMA), and Total Time in Bed (TIB). Total Sleep Time (TST) is calculated by subtracting SOL, WASO and EMA from TIB. | At baseline, weeks 1, 2, 3, and 4 (end of treatment) | 
| Generalized Anxiety Disorder Scale (GAD-7) | It is a concise anxiety self-assessment instrument consisting of 7 items to assess patients' anxiety over the past two weeks. This questionnaire has a score of 0-3 for each entry and a total score of 21. The scores are 5-9 for mild anxiety, 10-14 for moderate anxiety, and 15-21 for severe anxiety. | At baseline and week 4 (end of treatment) | 
| Patient Health Questionnaire-9 (PHQ-9) | It is a simple and validated 9-item depression self-assessment tool that assesses patients' depression over the past 2 weeks. Each item is scored 0-3, with a total score of 27. Among them, 5-9 are mild depression, 10-14 are moderate depression, 15-19 are severe depression, and 20-27 are very severe depression. | At baseline and week 4 (end of treatment) | 
| Quality of Life Core Scale (QLQ-C30) | It contains 30 entries with six dimensions. Widely used in clinical studies, it is currently used to assess the quality of life situation of patients. | At baseline and week 4 (end of treatment) | 
| Sleep Efficiency (SE) with Actigraphy | The actigraphy device (wGT3X-BT. LLC, Pensacola, USA) can monitor sleep quality objectively. Sleep Efficiency(SE) is the percentage of time spent asleep while in bed. It is calculated by (TST / TIB) × 100%. The actigraphy device record Sleep Onset Latency (SOL),Wake After Sleep Onset(WASO), Early morning awakening(EMA), and Total Time in Bed (TIB). Total Sleep Time (TST) is calculated by subtracting SOL, WASO and EMA from TIB. | At baseline, weeks 1 and 4 (end of treatment) | 
| Weekly usage of remedial drugs | The percentage of participants who used emergency drugs. | At weeks 1, 2, 3, and 4 (end of treatment), week 8 (follow-up), and week 16(follow-up) | 
| Incidence of adverse events | The adverse events (AEs) assessment aims at evaluating the AEs of acupuncture treatment. | During 1-4 weeks | 
| Treatment response rate of Insomnia Severity Index (ISI) at follow-up visits | The percentage of people whose total Insomnia Severity Index (ISI) score decreased by ≥8 points at the end of week 8 and 16 of the treatment compared to the baseline score. The ISI consists of 7 items to assess the nature and symptoms of the subject's sleep disorders. Questions addressed subjects' subjective ratings of sleep quality, including the severity of symptoms, subjects' satisfaction with their sleep patterns, the impact of the degree of insomnia on daily functioning, subjects' awareness of the impact of insomnia on themselves, and their level of frustration due to their sleep disorders. The scores were 0 to 4, with a total score range from 0 to 28. Higher scores indicate more severe insomnia. ISI levels can be classified as no clinically significant insomnia (0 to 7), mild insomnia (8 to 14), moderate insomnia (15 to 21), and severe insomnia (22 to 28). | Week 8 (follow-up), and week 16(follow-up) | 
| The mean changes of Insomnia Severity Index (ISI) from baseline | The ISI consists of 7 items to assess the nature and symptoms of the subject's sleep disorders. Questions addressed subjects' subjective ratings of sleep quality, including the severity of symptoms, subjects' satisfaction with their sleep patterns, the impact of the degree of insomnia on daily functioning, subjects' awareness of the impact of insomnia on themselves, and their level of frustration due to their sleep disorders. The scores were 0 to 4, with a total score range from 0 to 28. Higher scores indicate more severe insomnia. ISI levels can be classified as no clinically significant insomnia (0 to 7), mild insomnia (8 to 14), moderate insomnia (15 to 21), and severe insomnia (22 to 28). | Week 4 (end of treatment), week 8 (follow-up), and week 16(follow-up) | 
| Sleep Awakening (SA) with Actigraphy | It is the number of sleep awakenings during the night that recorded with actigraphy device (wGT3X-BT. LLC, Pensacola, USA). | At baseline, weeks 1 and 4 (end of treatment) | 
| Average Awaken Time (AA) with Actigraphy | It is estimated by (Wake After Sleep Onset(WASO) / Sleep Awakening(SA)) measured in minutes that recorded with actigraphy device (wGT3X-BT. LLC, Pensacola, USA). | At baseline, weeks 1 and 4 (end of treatment) |