Cancer, Chemotherapy-induced Peripheral Neuropathy (CIPN)
Conditions
Keywords
Chemotherapy-induced peripheral neuropathy, Acupuncture, Exercise training
Brief summary
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment that causes numbness, pain, and balance issues in a patient's hands and feet. This study focuses on finding a non-drug approach to help cancer survivors manage these uncomfortable symptoms. The main purpose of this research is to evaluate whether combining Electroacupuncture(EA) with a exercise training program works better than using electroacupuncture alone. Electroacupuncture uses gentle electrical pulses through acupuncture needles to stimulate nerves, while the exercise program aims to improve a patient's balance, physical strength, and movement safety. Participants will be randomly assigned to receive either the combination therapy or electroacupuncture alone. The study involves scheduled hospital visits along with home-based practice guided by instructional videos. The researchers aim to evaluate the efficacy of combined EA and exercise training program on neurological symptoms and quality of life in CIPN patients across different CTCAE grades.
Detailed description
I. Rationale and Synergistic Mechanisms Chemotherapy-induced peripheral neuropathy (CIPN) represents a highly prevalent and debilitating neurotoxic syndrome in cancer survivors treated with taxanes or platinum-based agents. Clinically, it presents as persistent symmetrical paresthesia, burning sensations, neuropathic pain, and significant proprioceptive deficits in the extremities. While conventional pharmacological management frequently yields suboptimal efficacy or introduces intolerable central nervous system adverse effects, this protocol investigates a non-pharmacological, integrative medical strategy combining Electro-Acupuncture (EA) with progressive multi-modal exercise training. The scientific rationale predicates on a dual-pathway synergistic mechanism: EA serves as an internal neuro-modulatory intervention that delivers stable micro-currents to deep acupoints, thereby stimulating the endogenous opioid system, down-regulating systemic and local pro-inflammatory cytokines, optimizing microcirculation, and facilitating axonal myelin sheath regeneration. Concurrently, the progressive exercise training serves as an external functional rehabilitation mechanism. By driving neuromuscular retraining, exercise reinforces cortical-peripheral functional connectivity and enhances dynamic postural control, thereby counteracting the structural proprioceptive deficits unaddressed by acupuncture alone. II. Technical Standardization of Interventions The therapeutic protocol is rigorously standardized over an 8-week duration, leveraging an integrated in-hospital and digital home-based framework to guarantee a uniform total dosage of three intervention sessions per week for all participants. A. Electroacupuncture (EA) Protocol: Acupuncture is delivered by certified clinical practitioners targeting predefined bilateral acupoints to elicit the characteristic "de-qi" sensation (soreness, numbness, distension). Stimulus is applied via an electrical stimulator configured to a dense-disperse wave frequency of 2/100 Hz for a fixed duration of 20 minutes. 1. Upper Extremity Acupoints: Quze (PC3), Neiguan (PC6), and Daling (PC7). 2. Lower Extremity Acupoints: Zusanli (ST36), Sanyinjiao (SP6), Taixi (KI3), and Taichong (LR3). 3. Frequency Allocation: The protocol's frequency is determined by the in-hospital attendance cohorts. Participants under Tier 1 are allocated to receive 1 in-hospital session/week, whereas participants under Tier 2 are allocated to receive 2 in-hospital sessions/week. B. Progressive Multi-Modal Exercise Training (Experimental Group Only): Immediately following the termination of EA, participants engage in 30 minutes of supervised, progressive balance and neuromuscular exercises. The exercise intensity is strictly regulated within a moderate range, corresponding to a Rating of Perceived Exertion (RPE) of 11 to 14. The dynamic regimen incorporates: 1. Multi-directional single-leg stepping tasks. 2. Single-leg stance coupled with active trunk rotation control. 3. Dynamic balance training integrated with synchronous upper extremity proprioceptive tasks and visual tracking. 4. Progressive lunge ambulation combined with axial trunk rotations. 5. Unilateral cross-knee touch balance-strength maneuvers. C. Digital Home Support and Dosage Synchronization: To equalize the cumulative therapeutic volume across different baseline severity cohorts, a structured home support system is deployed via a dedicated intelligent digital platform: 1. Tier 1 : Completes 1 in-hospital session and 2 home-based sessions per week. 2. Tier 2 : Completes 2 in-hospital sessions and 1 home-based session per week. Home compliance is enforced via customized QR codes linking to institutional instructional videos for standardized exercise execution and complementary acupressure. Participants maintain a structured electronic "Home Exercise Diary" to log adherence, task completion frequencies, and subjective post-exercise fatigue. III. Statistical Analysis Considerations To accommodate clinical attrition common among oncology patient populations undergoing post-chemotherapy surveillance, the total sample size incorporates an anticipated 15% drop-out rate to secure evaluable final data datasets. The longitudinal therapeutic effects across multiple discrete intervals (Baseline, Week 4, and Week 8) will be primarily evaluated using Repeated Measures Analysis of Variance (RM-ANOVA) to isolate inter-group and intra-group variances. Subgroup analyses will be systematically executed based on baseline symptom stratifications to detect severity-specific treatment responses, with Pearson's correlation coefficients utilized to ascertain the specific mathematical relationship between home exercise compliance and functional balance increments.
Interventions
DEVICEElectroacupuncture
A standardized electroacupuncture stimulation administered to specific upper limb acupoints (PC6, LI11, HT7) and lower limb acupoints (ST36, SP6, KI3, LR3) for 20 minutes per session. A dense-disperse wave profile at a frequency of 2/100 Hz is applied, with the intensity adjusted to the participant's maximum comfortable level without inducing pain ("De-Qi" sensation).
BEHAVIORALExercise Training
A 30-minute structured, progressive exercise regimen focusing on balance, muscle strength, sensory integration, and coordination. The program features moderate-intensity activities (RPE 11-14) including multi-directional stepping, trunk rotation control, dynamic balance integrated with upper limb proprioception/visual tracking, progressive squat-walking, and cross-knee touch balance training.
BEHAVIORALStructured Home-Based Health Education and Dose-Controlled Exercise Program
Participants in the experimental group will receive a structured home support and health education program designed to enhance the therapeutic effects of the in-hospital intervention. The intervention includes: Daily Safety and Protection Guidance: Education on environmental safety and peripheral neuropathy protection . Dose-Controlled Home Exercise \& Acupressure: Participants will practice home-based exercises and acupressure guided by instructional videos via QR codes. To maintain an identical total weekly intervention dose across the group, the frequency is tailored based on stratification: Tier 1 (1 in-hospital session) will practice 2 times/week at home; Tier 2 (2 in-hospital sessions) will practice 1 time/week at home. This ensures a total exercise volume of 3 sessions per week for all participants in this group. Home Exercise Log: Participants are required to maintain a daily log to track practice frequency and recording subjective feedback.
BEHAVIORALGeneral Health Education
Participants in the control group will receive routine, standard-of-care health education delivered by clinical staff during their hospital visits. This educational session covers general, non-structured advice on daily care and safety precautions for patients undergoing chemotherapy.
Sponsors
Show Chwan Memorial Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Due to the nature of electro-acupuncture and progressive balance training, blinding of the therapists (acupuncturists and physical therapists) and participants is not feasible. Therefore, this study adopts a single-blind (outcomes assessor-blinded) design. To maintain masking, outcomes assessors responsible for performing the neurological assessments and functional tests (including TNS-r, Mini-BESTest, and Semmes-Weinstein Monofilaments) are strictly separated from the therapists administering the interventions. These assessors perform all measurements in an independent, designated examination room and are prohibited from discussing group allocations with the participants. Furthermore, participants are explicitly instructed during education sessions not to disclose or discuss their specific treatment components with the assessors during any follow-up evaluations.
Intervention model description
This prospective, stratified randomized controlled trial (1:1 allocation) evaluates the synergistic efficacy of Electroacupuncture (EA) combined with progressive exercise training for chemotherapy-induced peripheral neuropathy (CIPN). Participants are stratified into two discrete tiers based on baseline CTCAE severity grades to minimize data deviation and optimize decision-making: Tier 1 (1 in-hospital) and Tier 2 (2 in-hospital). Within each tier, a third-party researcher uses a computer-generated sequence (block size of 4) to assign participants to the Experimental Group (EA + progressive exercise training) or Control Group (EA only). To ensure dosage consistency, weekly intervention frequency is tailored to the severity tier via a digital platform, standardizing the total cumulative exercise volume for both Tier 1 (1 in-hospital + 2 home sessions) and Tier 2 (2 in-hospital + 1 home session) to exactly 3 sessions per week.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed cancer diagnosis with prior taxane or platinum-based chemotherapy. 2. CIPN symptoms staged as CTCAE Grade 1, 2, or 3. 3. Life expectancy \> 6 months and capable of independent ambulation.
Exclusion criteria
1. Presence of a cardiac pacemaker. 2. Severe coagulation disorders. 3. Neuropathy from other etiologies (non-chemotherapy induced).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Neuropathy Score-reduced (TNS-r) | Baseline (Week 0), Mid-intervention (Week 4), and Post-intervention (Week 8). | The Total Neuropathy Score-reduced (TNS-r) is a validated clinical composite scale used in this study to quantitatively assess the severity of chemotherapy-induced peripheral neuropathy (CIPN). It integrates patient-reported symptoms with objective clinical signs, including ankle reflexes, pinprick and vibration thresholds, muscle strength, and nerve conduction. The assessment evaluates seven items, each graded on a scale from 0 (normal or no symptoms) to 4 (very severe). This grading provides a standardized measure where higher scores indicate more severe peripheral nerve impairment and neurological symptoms. In this trial, the TNS-r serves as the primary outcome measure to determine if the combined electro-acupuncture and exercise intervention effectively reduces neurological symptoms and promotes nerve repair over the 8-week study period. |
| Mini-Balance Evaluation Systems Test (Mini-BESTest) | Baseline (Week 0), Mid-intervention (Week 4), and Post-intervention (Week 8). | The Mini-Balance Evaluation Systems Test (Mini-BESTest) is a 14-item clinical instrument validated to quantitatively assess dynamic balance across four distinct contexts: anticipatory postural adjustments, reactive postural control, sensory orientation, and dynamic gait. Each item is scored from 0 to 2, yielding a total score range of 0 to 28, where higher scores represent superior dynamic postural control, enhanced functional mobility, and a reduced risk of falls. In this trial, the Mini-BESTest serves as a co-primary outcome measure to evaluate the external functional rehabilitation efficacy of combining electroacupuncture with progressive multi-modal exercise training. It specifically detects improvements in dynamic postural stability, neuromuscular control, and proprioception over the 8-week intervention period. |
| Semmes-Weinstein Monofilaments | Baseline (Week 0), Mid-intervention (Week 4), and Post-intervention (Week 8). | Tactile sensation and sensory thresholds are objectively measured at specific anatomical sites on the bilateral upper and lower extremities using Semmes-Weinstein Monofilaments (SWM). Results will be analyzed based on the smallest filament size perceived by the participant. Lower filament values indicate finer tactile discrimination and improved sensory neurological function. |
| Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity(FACT/GOG-NTX) | Baseline (Week 0), Mid-intervention (Week 4), and Post-intervention (Week 8). | This questionnaire specifically measures the impact of chemotherapy-induced neurotoxicity on a participant's daily functional status. It comprises five subscales: Physical Well-Being (7 items, scored 0-4), Social/Family Well-Being (7 items, scored 0-4), Emotional Well-Being (6 items, scored 0-4), Functional Well-Being (7 items, scored 0-4), and an Additional Concerns/Neurotoxicity subscale (NTX subscale: 11 items assessing numbness, tingling, and dexterity, scored 0-4). Individual items are scored such that higher scores on well-being items and reverse-scored neurotoxicity items represent less symptom distress, reduced neurotoxic impact, and a higher level of daily functional well-being. |
| European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Baseline (Week 0), Mid-intervention (Week 4), and Post-intervention (Week 8). | This 30-item instrument evaluates the overall physical, psychological, and social functional status of cancer patients. Items 1-28 are scored on a 4-point scale (1: Not at all, to 4: Very much), and items 29-30 assess global health status and overall quality of life on a 7-point scale (1: Very poor, to 7: Excellent). All scores are linearly transformed to a 0-100 scale according to the EORTC scoring manual. For functional scales and global quality of life, higher scores represent better functioning; for symptom scales (e.g., pain, fatigue, insomnia), higher scores indicate greater symptom severity and distress. |
| World Health Organization Quality of Life-BREF (WHOQOL-BREF) | Baseline (Week 0), Mid-intervention (Week 4), and Post-intervention (Week 8). | This questionnaire measures the participant's subjective life satisfaction across four comprehensive domains: Physical Health, Psychological, Social Relationships, and Environment. It includes 26 core items scored on a 5-point Likert scale (1 to 5), plus 2 local items assessing respect and food availability (scored 1 to 5). Domain scores are calculated and transformed into a scale ranging from 4 to 20, aligned with the WHOQOL scoring guideline. Higher domain scores indicate a better subjective perception of quality of life and higher satisfaction. |
Countries
Taiwan
Contacts
CONTACTI-Ting Lee, Bachelor
CONTACTCHI-CHUAN, KAO
PRINCIPAL_INVESTIGATORI-Ting Lee
Changhua Show Chwan Memorial Hospital
Outcome results
None listed