The goal of this clinical trial is to evaluate the clinical effectiveness and understand the biological mechanisms of electroacupuncture (EA) in reducing cognitive toxicity among cancer survivors. The study aims are: * To evaluate the clinical effectiveness of a 10-week EA regimen targeting neuropsychiatric-related acupoints in reducing cognitive toxicity among cancer survivors in Singapore. * To explore the biological mechanisms underlying EA's effects on cognitive function. * To assess the early implementation of EA for managing cognitive toxicity in cancer survivors. Researchers will compare results from the true EA arm, sham EA arm and waitlist control arm, to see if electroacupuncture can help improve cognitive issues related to cancer and its treatment, how it may work, and what factors may affect how it is delivered in cancer care. Participants will: * Be assigned to either of the 3 arms (true EA, sham EA, waitlist control) * Received 10 EA sessions (if assigned to true or sham EA arm) * Complete 3 study assessment visits at baseline, Week 13, and Week 17 * Be invited to a one-time interview to share their study experience (optional, if selected)
Electroacupuncture (EA) is a promising, emerging intervention to manage cognitive toxicity among patients with cancer. The primary goal of the EAST-ALIGN study is to evaluate the clinical effectiveness and understand the biological mechanisms of EA in reducing cognitive toxicity among cancer survivors through a randomized, blinded sham and waitlist controlled, clinical trial. Simultaneously, the investigators will collect implementation data on engaging community Traditional Chinese Medicine (TCM) practitioners to deliver EA. This approach facilitates the early identification and resolution of implementation barriers, accelerating EA adoption into clinical practice if proven effective.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
DOUBLE
Enrollment
168
Electroacupuncture is administered at 13 predefined acupoints: Shenting (GV24), Baihui (DU20), Sishencong (EX-HN1), Zhongwan (CV12), Guanyuan (CV4), Neiguan (PC6, bilateral), Shenmen (HT7, bilateral), Zusanli (ST36, bilateral), Sanyinjiao (SP6, bilateral), Taixi (KI3, bilateral), Zhaohai (KI6, bilateral), Hegu (LI4, bilateral), and Taichong (LIV3, bilateral.
Electroacupuncture is administered at predefined non-disease related acupoints: Pianli (LI6) bilateral, Wenliu (LI7) bilateral, Futu (ST32) bilateral, Xiajuxu (ST39) bilateral, Daheng (SP15) bilateral, and Jiaosun (TE20) bilateral.
National Cancer Center Singapore
Singapore, Singapore
Objective cognitive function - multitasking
Assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB®) Multitasking Test, a computerized cognitive testing software. Score ranges from 0-160, with a lower score reflecting better performance. Clinically significant improvement is defined as a Reliable Change Index (RCI) exceeding 1.96 from baseline in at least one out of five tests (including this Multitasking Test).
Time frame: Baseline, 13 weeks after baseline, and 17 weeks after baseline.
Objective cognitive function - learning and memory
Assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB®) Paired Associates Learning Test, a computerized cognitive testing software. Score ranges from 0-70, with a lower score reflecting better performance. Clinically significant improvement is defined as a Reliable Change Index (RCI) exceeding 1.96 from baseline in at least one out of five tests (including this Paired Associates Learning Test).
Time frame: Baseline, 13 weeks after baseline, and 17 weeks after baseline.
Objective cognitive function - sustained attention
Assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB®) Rapid Visual Information Processing Test, a computerized cognitive testing software. Score ranges from 0-1, with a higher score reflecting better performance. Clinically significant improvement is defined as a Reliable Change Index (RCI) exceeding 1.96 from baseline in at least one out of five tests (including this Rapid Visual Information Processing Test).
Time frame: Baseline, 13 weeks after baseline, and 17 weeks after baseline.
Objective cognitive function - response speed
Assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB®) Reaction Time Test, a computerized cognitive testing software. Score ranges from 100-5100 ms, with a lower score reflecting faster reaction time. Clinically significant improvement is defined as a Reliable Change Index (RCI) exceeding 1.96 from baseline in at least one out of five tests (including this Reaction Time Test).
Time frame: Baseline, 13 weeks after baseline, and 17 weeks after baseline.
Objective cognitive function - working memory
Assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB®) Spatial Working Memory Test, a computerized cognitive testing software. Score ranges from 0-153, with a lower score reflecting better performance. Clinically significant improvement is defined as a Reliable Change Index (RCI) exceeding 1.96 from baseline in at least one out of five tests (including this Spatial Working Memory Test).
Time frame: Baseline, 13 weeks after baseline, and 17 weeks after baseline.
Subjective cognitive function
The Functional Assessment of Cancer Therapy-Cognition (FACT-Cog) version 3 is a validated 37-item questionnaire assessing self-perceived subjective cognitive function. The total FACT-Cog score is summed from all items (range: 0-148), with higher scores indicating better subjective cognitive functioning.
Time frame: Baseline, 13 weeks after baseline, and 17 weeks after baseline.
Fatigue
The Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) is a validated questionnaire that comprises 30 items and contains 5 subscales, each with 6 items: general fatigue, physical fatigue, emotional fatigue, mental fatigue, and vigor. The total MFSI-SF score is obtained by subtracting the vigor subscale from the sum of all items (range: 24-96), with a higher score indicating higher fatigue level.
Time frame: Baseline, 13 weeks after baseline, and 17 weeks after baseline.
Symptom burden
The Rotterdam Symptom Checklist (RSCL) is a validated self-report measure of quality of life in patients with cancer. It includes 30 symptom items, 8 activity items, and 1 overall quality-of-life item. The symptom distress score combines the physical symptom distress scale (23 items, range 23-92) and, psychological distress scale (7 items, range 7-28), for a total range of 30-120. Higher scores indicate greater symptom burden, distress, or quality of life.
Time frame: Baseline, 13 weeks after baseline, and 17 weeks after baseline.
Work productivity
The Work Productivity and Activity Impairment (WPAI) questionnaire is a patient-reported outcome measure that assesses the impact of health problems on work productivity and regular activities, including absenteeism, presenteeism, overall work impairment, and activity impairment. Scores in each of these four areas are expressed as a percentage from 0% to 100%, with higher scores indicating greater impairment and worse productivity.
Time frame: Baseline, 13 weeks after baseline, and 17 weeks after baseline.
Health utility
EuroQOL Group 5-Dimension (EQ-5D-5L) contains a 5-item descriptive system measuring 5 dimensions: mobility, self-care, usual activities, pain/ discomfort, anxiety/ depression; a visual analogue scale (VAS) measuring overall health status. EQ-5D Index Value (Utility Score) ranges from 0 to 1.0 with higher value indicating better health-related quality of life. The VAS ranges from 0 to 100, with higher scores reflecting better self-rated health.
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Time frame: Baseline, 13 weeks after baseline, and 17 weeks after baseline.
Biomarkers - plasma BDNF
Plasma brain-derived neurotropic factor levels at each time point will be analyzed from blood samples collected.
Time frame: Baseline, 13 weeks after baseline, and 17 weeks after baseline.
Biomarkers - plasma cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-alpha)
Plasma concentrations of interleukin-1 beta (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha) will be measured from blood samples. Each cytokine will be reported in picograms per milliliter (pg/mL). Higher values indicate higher plasma cytokine concentrations.
Time frame: Baseline, 13 weeks after baseline, and 17 weeks after baseline.
Biomarkers - epigenetic ageing
Epigenetic ageing will be assessed using DNA methylation-based biological age metrics derived from blood samples.
Time frame: Baseline, 13 weeks after baseline, and 17 weeks after baseline.
Safety assessment
Participants will be monitored for adverse events and the severity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE).
Time frame: 13 weeks after baseline and 17 weeks after baseline.
Implementation - acceptability of electroacupuncture treatment
Participants in the true and sham EA arms will complete a questionnaire evaluating their perceptions towards the true/sham EA treatment. Participants will be asked if they are satisfied and benefited from the treatment, and whether they would consider undergoing treatment again outside of a trial setting.
Time frame: 13 weeks after baseline.
Implementation - adoption of EA
Adoption will be evaluated by tracking study enrollment logs, including the number of eligible individuals approached, the number recruited, and documented reasons for non-participation when available.
Time frame: From commencement of study recruitment till the end of recruitment, assessed up to 3 years.
Implementation - treatment fidelity
Treatment fidelity will be assessed from standardized treatment logs for each true/sham EA session by the TCM practitioners. For blinding assessment, participants in the true and sham EA arms will be asked to guess their treatment arm allocation (True EA/ Sham EA/ Don't know).
Time frame: 13 weeks after baseline.
Implementation - feasibility
Semi-structured interviews conducted using an interview guide developed based on the Consolidated Framework for Implementation Research (CFIR). Semi-structured interviews with key stakeholders (TCM practitioners, tertiary healthcare providers, clinical operations staff) to identify barriers and facilitators to integrating EA into routine oncology care.
Time frame: 17 weeks after baseline, through study completion, estimated as up to 3 years.
Implementation - implementation cost
Implementation cost will be assessed using a time-driven activity-based costing approach. A structured activity log will be maintained by study personnel to document the time and resources required for each implementation activity, including personnel effort and fixed consumable resources.
Time frame: From commencement of study recruitment, through study completion, estimated as up to 3 years.