Cancer-related Cognitive Impairment
Conditions
Keywords
Electroacupuncture, Acupuncture, Traditional Chinese Medicine, Cancer-related Cognitive Impairment, Cognitive Toxicity, Oncology, Survivor
Brief summary
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)
Detailed description
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.
Interventions
DEVICETrue electroacupuncture
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.
DEVICESham electroacupuncture
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.
Sponsors
National Cancer Centre, Singapore
Singapore Thong Chai Medical Institution
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
This is a randomized, sham- and waitlist-controlled trial.
Eligibility
Sex/Gender
ALL
Age
21 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Survivor participants * Aged 21-85 years * Documented cancer diagnosis in electronic health records * Perceived by the survivor or oncology care provider that cognitive function has worsened since cancer diagnosis and/or beginning of cancer treatment * Able to understand English or Mandarin * Able to provide informed consent Stakeholder participants * Aged ≥21 years * Identified as having a relevant role, experience, or perspective relating to the delivery, referral, coordination, or implementation of EA or supportive cancer care in the study context * Able to provide informed consent
Exclusion criteria
Survivor participants * Presence of brain metastases * Severe needle phobia * Known bleeding disorder (e.g. hemophilia, von Willebrand disease, thrombocytopenia). * Current use of antiplatelet or anticoagulant therapy (e.g. aspirin, clopidogrel, warfarin, enoxaparin, rivaroxaban, dabigatran) * Known blood-borne communicable disease (e.g. hepatitis B, hepatitis C, human immunodeficiency virus) * Presence of a pacemaker or other electronic implant, or a history of epilepsy * Current acupuncture treatment or acupuncture received within the past 3 months * Current pregnancy, planned pregnancy over the next 5 months, or breastfeeding. * Incapable of providing informed consent * Unable to complete study procedures Stakeholder participants * Incapable of providing informed consent * Unable to complete study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective cognitive function - multitasking | Baseline, 13 weeks after baseline, and 17 weeks after baseline. | 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). |
| Objective cognitive function - learning and memory | Baseline, 13 weeks after baseline, and 17 weeks after baseline. | 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). |
| Objective cognitive function - sustained attention | Baseline, 13 weeks after baseline, and 17 weeks after baseline. | 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). |
| Objective cognitive function - response speed | Baseline, 13 weeks after baseline, and 17 weeks after baseline. | 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). |
| Objective cognitive function - working memory | Baseline, 13 weeks after baseline, and 17 weeks after baseline. | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Implementation - adoption of EA | From commencement of study recruitment till the end of recruitment, assessed up to 3 years. | 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. |
| Implementation - treatment fidelity | 13 weeks after baseline. | 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). |
| Implementation - feasibility | 17 weeks after baseline, through study completion, estimated as up to 3 years. | 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. |
| Implementation - implementation cost | From commencement of study recruitment, through study completion, estimated as up to 3 years. | 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. |
| Subjective cognitive function | Baseline, 13 weeks after baseline, and 17 weeks after baseline. | 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. |
| Fatigue | Baseline, 13 weeks after baseline, and 17 weeks after baseline. | 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. |
| Symptom burden | Baseline, 13 weeks after baseline, and 17 weeks after baseline. | 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. |
| Work productivity | Baseline, 13 weeks after baseline, and 17 weeks after baseline. | 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. |
| Biomarkers - plasma BDNF | Baseline, 13 weeks after baseline, and 17 weeks after baseline. | Plasma brain-derived neurotropic factor levels at each time point will be analyzed from blood samples collected. |
| Health utility | Baseline, 13 weeks after baseline, and 17 weeks after baseline. | 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. |
| Biomarkers - plasma cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-alpha) | Baseline, 13 weeks after baseline, and 17 weeks after baseline. | 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. |
| Biomarkers - epigenetic ageing | Baseline, 13 weeks after baseline, and 17 weeks after baseline. | Epigenetic ageing will be assessed using DNA methylation-based biological age metrics derived from blood samples. |
| Safety assessment | 13 weeks after baseline and 17 weeks after baseline. | Participants will be monitored for adverse events and the severity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE). |
| Implementation - acceptability of electroacupuncture treatment | 13 weeks after baseline. | 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. |
Countries
Singapore
Contacts
CONTACTYu KE, PhD
CONTACTBenton PT TAM, MSc
STUDY_CHAIRYu KE, PhD
National Cancer Centre, Singapore
Outcome results
None listed