Effect of Acupuncture on Psychoneurological Symptom Cluster in Breast Cancer Survivors

Overview

This clinical trial aims to assess whether electroacupuncture (EA) can alleviate the psychoneurological symptom cluster (including pain, fatigue, insomnia, anxiety, depression and subjective cognitive decline) in breast cancer survivors, and to evaluate the safety of this therapy. Researchers will conduct a randomized controlled trial of electroacupuncture (EA) as compared to sham electroacupuncture (SA) in breast cancer survivors with the psychoneurological symptom cluster who are currently being treated with endocrine therapy. Participants will receive 16 treatments over 8 weeks. The EA group will receive true acupuncture with continuous wave stimulation (2Hz, intensity as tolerated) administered for 30 minutes per session. The SA group will receive sham acupuncture using blunt (non-penetrating) needles that contact the skin without penetration, along with a 30-second transient device activation instead of the 30-minute continuous stimulation. Treatment outcomes for pain, fatigue, insomnia, anxiety, depression and subjective cognitive function will be assessed. The primary outcome is response rate of the psychoneurological symptom cluster after 8 weeks of treatment. Secondary outcomes include changes from baseline in the scores of each of the six psychoneurological symptoms.

Interventions

• Device electroacupuncture
  A semi-standardized protocol is used for participants in the EA group, which includes (1) standardized acupoints (Midline: Baihui \[GV20\], Shenting \[GV24\], Qihai \[CV6\], Guanyuan \[CV4\]; Bilateral: Fengchi \[GB20\], Taiyang \[EX-HN5\], Zusanli \[ST36\], Hegu \[LI4\], Taichong \[LR3\]); and (2) additional acupoints (Sishencong \[EX-HN1\] and bilateral Benshen \[GB13\] for anxiety/depression/subjective cognitive decline; 1-2 Ashi points for pain; no additional points for insomnia/fatigue). Me
• Device sham electroacupuncture
  In the SA group, noninsertive simulated acupuncture and sham electrical stimulation(30-second transient device activation instead of 30-minute continuous stimulation) are used, while maintaining the same treatment duration and course as the EA group. Blunt needles are placed on 12 acupoints (Bilateral: Fengchi \[GB20\], Taiyang \[EX-HN5\], Zusanli \[ST36\], Hegu \[LI4\], Taichong \[LR3\]; Midline: Qihai \[CV6\], Guanyuan \[CV4\]) without skin penetration. Electrical stimulation is conducted on t

Primary outcome measures

• Response rate of psychoneurological symptom cluster (after 8 weeks of treatment) [Time frame: Week 8]

Secondary outcome measures (11)

• Response rate of psychoneurological symptom cluster (after 4 weeks of treatment and 12-week follow-up) [Time frame: Week 4, Week 12]
• Change from Baseline in the Functional Assessment of Cancer Therapy-Breast (FACT-B) Score [Time frame: Baseline (Week 0), Week 4, Week 8, Week 12]
• Change from Baseline in the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Total and Subscale Scores [Time frame: Baseline (Week 0), Week 4, Week 8, Week 12]
• Change from Baseline in the Visual Analogue Scale (VAS) Score for Cancer/Treatment-Related Pain [Time frame: Baseline (Week 0), Week 2, Week 4, Week 6, Week 8, Week 12]
• Change from Baseline in the Pittsburgh Sleep Quality Index (PSQI) Score [Time frame: Baseline (Week 0), Week 2, Week 4, Week 6, Week 8, Week 12]
• Change from Baseline in the Brief Fatigue Inventory-Chinese Version (BFI-C) Score [Time frame: Baseline (Week 0), Week 2, Week 4, Week 6, Week 8, Week 12]
• Change from Baseline in the Hospital Anxiety and Depression Scale-Anxiety Subscale (HADS-A) Score [Time frame: Baseline (Week 0), Week 2, Week 4, Week 6, Week 8, Week 12]
• Change from Baseline in the Hospital Anxiety and Depression Scale-Depression Subscale (HADS-D) Score [Time frame: Baseline (Week 0), Week 2, Week 4, Week 6, Week 8, Week 12]
• Acupuncture Expectation Evaluation [Time frame: Within 5 minutes after the first treatment]
• Blinding assessment [Time frame: Within 5 minutes after the first treatment， Within 5 minutes after the last treatment]
• Safety Assessment [Time frame: The entire study period (Week 0 [Baseline] to Week 12 [Follow-up])]

Eligibility criteria

Inclusion Criteria：

• Female, aged 18-75 years;
• Histologically confirmed Stage 0, I, II, or III breast cancer (according to the AJCC 8th edition)；
• Completed active treatment (surgery, chemotherapy, and/or radiotherapy) at least 1 month prior to study initiation , and are currently receiving endocrine therapy；
• Meet at least 2 of the following 6 criteria:

(1)Visual Analogue Scale (VAS) score for pain ≥ 4 (2)Pittsburgh Sleep Quality Index (PSQI) score ≥ 8 (3)Brief Fatigue Inventory-Chinese version (BFI-C) score ≥ 4 (4)Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A) score ≥ 8 (5)Hospital Anxiety and Depression Scale-Depression subscale (HADS-D) score ≥ 8 (6)Functional Assessment of Cancer Therapy-Cognitive Function-Perceived Cognitive Impairments (FACT-Cog-PCI) score < 60 ; 5.Has signed the informed consent form and voluntarily participates in this study.

Exclusion criteria

• History of psychiatric disorders (e.g., bipolar disorder, schizophrenia, substance addiction)
• Presence of diseases that may impair cognitive function or interfere with study assessments (e.g., Alzheimer's disease, Parkinson's disease, brain tumors).
• Fatigue attributable to a treatable condition (e.g., hypothyroidism).
• Severe debilitation or significant organic disease (e.g., heart failure, severe hepatic/renal insufficiency, severe anemia, uncontrolled infection).
• Use of anxiolytics, antidepressants, psychostimulants, or sedative-hypnotics within the past 4 weeks.
• Chronic use of corticosteroids.
• Prior acupuncture treatment within 3 months, or participation in an acupuncture or drug clinical trial within 6 months.
• History of hemorrhagic disease, severe coagulation dysfunction, or current use of anticoagulants (e.g., warfarin).
• Implanted cardiac pacemaker.
• Pregnancy or breastfeeding.
• Concurrent participation in another clinical study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 6 centers

• Senior Department of Oncology，Chinese PLA General Hospital — Beijing
• Xiyuan Hospital of CACMS — Beijing
• Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University) — Nanjing
• Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingda — Qingdao
• Tianjin Medical University Cancer Institute & Hospital (TMUCIH) — Tianjin
• First Teaching Hospital of Tianjin University of Traditional Chinese Medicine — Tianjin

Publications

• Lu Y, Zhao Q, Zou J, Yan S, Tamaresis JS, Nelson L, Tu XM, Chen J, Tian L. A Composite Endpoint for Treatment Benefit According to Patient Preference. Stat Biopharm Res. 2022;14(4):408-422. doi: 10.1080/19466315.2022.2085783. Epub 2022 Jul 19. PMID 37981982
• Kwon KK, Lacey J, Kerin-Ayres K, Heller G, Grant S. Acupuncture for the treatment of the pain-fatigue-sleep disturbance-numbness/tingling symptom cluster in breast cancer survivors: a feasibility trial. Support Care Cancer. 2024 May 7;32(6):332. doi: 10.1007/s00520-024-08529-9. PMID 38713422
• Li H, Doorenbos AZ, Chen Z, Choi H, Ma W, Danciu O, Patil CL, Gao S, Lif N, Schlaeger JM. Feasibility and Acceptability of Integrating Acupuncture for Management of Multiple Symptoms in Medically Underserved Breast Cancer Survivors. Cancers (Basel). 2025 Jan 18;17(2):304. doi: 10.3390/cancers17020304. PMID 39858086
• Liao HY, Satyanarayanan SK, Lin YW, Su KP. Clinical efficacy and immune effects of acupuncture in patients with comorbid chronic pain and major depression disorder: A double-blinded, randomized controlled crossover study. Brain Behav Immun. 2023 May;110:339-347. doi: 10.1016/j.bbi.2023.03.016. Epub 2023 Mar 21. PMID 36948325
• Cui J, Song W, Jin Y, Xu H, Fan K, Lin D, Hao Z, Lin J. Research Progress on the Mechanism of the Acupuncture Regulating Neuro-Endocrine-Immune Network System. Vet Sci. 2021 Jul 30;8(8):149. doi: 10.3390/vetsci8080149. PMID 34437474
• Sun B, Cao X, Xin M, Guan R. Treatment of Depression with Acupuncture Based on Pathophysiological Mechanism. Int J Gen Med. 2024 Jan 31;17:347-357. doi: 10.2147/IJGM.S448031. eCollection 2024. PMID 38314195
• George MA, Lustberg MB, Orchard TS. Psychoneurological symptom cluster in breast cancer: the role of inflammation and diet. Breast Cancer Res Treat. 2020 Nov;184(1):1-9. doi: 10.1007/s10549-020-05808-x. Epub 2020 Aug 15. PMID 32803635
• Li H, Lockwood MB, Schlaeger JM, Liu T, Danciu OC, Doorenbos AZ. Tryptophan and Kynurenine Pathway Metabolites and Psychoneurological Symptoms Among Breast Cancer Survivors. Pain Manag Nurs. 2023 Feb;24(1):52-59. doi: 10.1016/j.pmn.2022.09.002. Epub 2022 Oct 10. PMID 36229337

Identifiers

NCT: NCT07481903 · 7252224

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗