Chemotherapy-induced NeuropathyCINNCT07877558

Home-Based Exercise and Vagus Nerve Stimulation for Chemotherapy-Induced Neuropathy

A study testing Active non-invasive vagus nerve stimulation (nVNS) and Home-based aerobic and resistance exercise program in people with Chemotherapy-induced Neuropathy, run by The Hong Kong Polytechnic University at 3 sites in Hong Kong.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Chemotherapy-induced Neuropathy
What is being tested?: Active non-invasive vagus nerve stimulation (nVNS) and Home-based aerobic and resistance exercise program
Type of treatment: Medical device, Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 60 participants
Where: 3 sitesHong Kong
Study dates: 21 Dec 2026to 20 Dec 2028
Phase: Interventional
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Hong Kong residents who can communicate in Cantonese, Mandarin, or English;
Aged 18 years or older;
Cancer survivors with complete disease remission after radical treatment;
Completed a chemotherapy regimen with radical intent that included at least one of the following agents for a minimum of 3 months:
Platinum compounds (e.g., cisplatin, carboplatin, oxaliplatin);
Taxanes (e.g., paclitaxel, docetaxel);

Show all 9Show fewer

Have CIN of at least grade 2 assessed by a clinician based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE 5.0), or self-rate ≥ 2 points on at least one item in the 4-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire;
Physically capable of engaging in exercise and assessments, as determined by the ability to complete the 6MWT;
Able to provide written informed consent.

Who cannot join

Known history of peripheral neuropathy or related symptoms prior to chemotherapy;
History of heart disease;
Bradycardia (heart rate < 60 beats per minute);
Pregnancy;
Presence of active implants, such as cardiac pacemakers, cochlear implants, and implanted neurostimulators;
Known metastasis to the central or peripheral nervous system;

Show all 13Show fewer

Any physical or mental handicap;
History of alcohol or illegal drug abuse;
Using a hearing aid device on the left ear;
Receiving other non-pharmacological treatments for CIN within the past 2 months;
Engaging in over 30 minutes of exercise for 2 or more days per week prior to enrollment;
Any wound, infection, skin allergy, or deformity in the left ear;
Any other medical contraindication to exercise and/or nVNS as determined by the treating oncologist.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Mian Wang, PhD contact

Hong Kong SAR, +852 6879 9254

robbie-m.wang@polyu.edu.hk

Fenglin Zhang, MPhil contact

Hong Kong SAR, +852 7018 5728

reyna.zhang@polyu.edu.hk

Hong Kong3 sites

Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital
Hong Kong
Sze Man Chan, +852 64600530, csm446@ha.org.hk
Department of Clinical Oncology, Tuen Mun Hospital
Hong Kong
Pui Shan Ho, +852 70724661, hps754@ha.org.hk
Department of Surgery, Kwong Wah Hospital
Hong Kong
Oi Kwan Chun, +852 46585123, cok702@ha.org.hk

Other trials in Hong Kong

About this study

Official title: Combining Home-Based Exercise and Non-Invasive Vagus Nerve Stimulation to Enhance Rehabilitation for Cancer Survivors With Chemotherapy-Induced Neuropathy: A Phase II Randomized Controlled Trial

Background: Studies highlight the potential benefits of home-based exercise for cancer survivors with chemotherapy-induced neuropathy (CIN); however, its effectiveness in alleviating CIN-related sensorimotor impairments and symptoms has been inconsistent and generally modest. Non-invasive vagus nerve stimulation (nVNS) has emerged as a promising adjunct for CIN rehabilitation. Preliminary studies suggest that nVNS can enhance the therapeutic effects of exercise-based rehabilitation, leading to greater improvements in sensorimotor impairments. A recent trial found that nVNS alleviated CIN-related pain and improved mental well-being, but did not significantly enhance physical well-being or clinician-rated CIN severity.

Objectives: To evaluate the efficacy, safety, and feasibility of combining home-based exercise with non-invasive vagus nerve stimulation (nVNS) to alleviate chemotherapy-induced neuropathy (CIN) and improve quality of life in cancer survivors.

Design and Subjects: This phase II randomized controlled trial will enroll 60 cancer survivors with established CIN following treatment with platinum compounds or taxanes. Participants will be randomly assigned in a 1:1:1 ratio to one of three groups: exercise with real nVNS (ERS), exercise with sham nVNS (ESS), or usual care.

Interventions: Participants in the experimental groups will engage in a 12-week home-based exercise program, with the ERS group receiving real nVNS and the ESS group receiving sham stimulation.

Study Instruments and Main Outcome Measures: The primary outcome, patient-reported CIN, will be assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-item (EORTC QLQ-CIPN20). Secondary outcomes will include the Total Neuropathy Score-nurse for clinician-reported CIN, the Symptom Distress Scale for general symptoms, functional performance measures (Timed Up and Go Test and 6-Minute Walk Test), and the EORTC QLQ-Core 30-item for quality of life.

Data Analysis and Expected Results: Generalized Estimating Equations will be used for efficacy outcome analysis. It is anticipated that the combined intervention may lead to improvements in CIN, functioning, and quality of life, thereby supporting further research in larger trials.

Conditions: Chemotherapy-induced Neuropathy
Being tested: Active non-invasive vagus nerve stimulation (nVNS), Sham non-invasive vagus nerve stimulation (nVNS), Home-based aerobic and resistance exercise program
Keywords: Chemotherapy-induced neuropathy, Exercise, Non-invasive vagus nerve stimulation, Cancer survivors, Phase II, Randomized controlled trial
Medical subject headings: Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Active non-invasive vagus nerve stimulation (nVNS)Device
nVNS will be applied to the left auricular region during the 12-week home-based exercise program. The ERS group will receive real stimulation at a frequency of 25 Hz, a pulse width of 250 µs, a pulse-train duration of 30 seconds on and 30 seconds off, and an intensity set at the maximum tolerable level for each participant (0.25-2.0 mA). Stimulation will be stopped during rest and after exercise. A portable device (tVNS501; Changzhou Rishena Medical Device Co., Ltd., Jiangsu, China) will be used to deliver the stimulation. During the first face-to-face training session, a trained research associate will configure the device parameters and position the electrode on the participant's left cymba concha. Subsequently, participants will be trained to self-administer the stimulation during home-based exercise.
Sham non-invasive vagus nerve stimulation (nVNS)Device
The ESS group will undergo sham stimulation using the same device and electrode placement as the ERS group. Sham stimulation will be administered by the same trained research associate during the first face-to-face training session and subsequently self-administered by the participants during the 12-week home-based exercise program. However, the stimulator will be set to deliver a low stimulation frequency of 1 Hz at an intensity that elicits only the minimum perceptible sensation, with the aim of inducing a subtherapeutic placebo effect by mimicking active stimulation. The pulse width will be set to the lowest output of the stimulator, 100 µs, and the pulse-train duration will be 10 seconds on and 50 seconds off, thereby minimizing any potential physiological effects.
Home-based aerobic and resistance exercise programBehavioural
The home-based exercise program includes aerobic and resistance training at moderate intensity (modified Borg 3-5/10). Aerobic: daily walking 30 min, initial step goal based on pre-intervention average daily steps, increased by 5-20% each week for 12 weeks, with self-monitoring of Borg and weekly follow-up guidance. Resistance: upper- and lower-body elastic band exercises (shoulder flexion/extension, horizontal abduction, elbow flexion/extension, heel raises, partial squats), 1-2 sets of 6 repetitions per set, completed within 1 minute, with 1-1.5 minutes of rest between sets, for a total of up to 30 minutes, progressing to a maximum of 15 repetitions per set. Participants receive an instruction booklet, three elastic bands, and a wrist pedometer. A 60-min face-to-face training session is delivered by a trained research associate at a study hospital, a university teaching room, or the participant's home.

Study groups in NCT07877558
Study group	Role	What they receive
Exercise with Real nVNS (ERS) group	Experimental	Participants will receive active non-invasive vagus nerve stimulation (nVNS) concurrently with a standardized 12-week home-based exercise program after baseline assessment and randomization. The exercise program will include moderate-intensity aerobic walking (30 min daily; initial step goal based on pre-intervention average daily steps; weekly increase of 5-20%) and resistance training, targeting Borg 3-5/10. Active nVNS will be applied to the left cymba concha using tVNS501 at 25 Hz with a pulse width of 250 µs, 30 seconds on and 30 seconds off, and an intensity of 0.25-2.0 mA (maximum tolerable level) during exercise. It will be stopped during rest and after exercise. Receives: Device: Active non-invasive vagus nerve stimulation (nVNS); Behavioral: Home-based aerobic and resistance exercise program
Exercise with Sham nVNS (ESS) group	Sham comparator	The ESS group will receive the same 12-week home-based exercise program as the ERS group following baseline assessment and randomization, including moderate-intensity aerobic walking and resistance training. However, the stimulator will deliver a low frequency of 1 Hz at an intensity that elicits only the minimum perceptible sensation, with the aim of inducing a subtherapeutic placebo effect by mimicking active stimulation. Sham stimulation will be administered by the same research associate during the first face-to-face training session, after which participants will self-administer it concurrently with the home-based exercise program. Receives: Device: Sham non-invasive vagus nerve stimulation (nVNS); Behavioral: Home-based aerobic and resistance exercise program
Usual Care (UC) group	No intervention	The UC group will receive routine follow-up and consultation with doctors and/or nurses, without any supplementary information regarding home-based exercise or nVNS during the study period. However, they will have the opportunity to access the home-based exercise program, including a face-to-face session and an instruction booklet containing information regarding only the home-based exercise program, but not nVNS stimulator operation, after completing the final post-intervention assessment at Week 12.

What is being measured

The primary outcome is the main question the study is designed to answer.

Patient-Reported Chemotherapy-Induced Neuropathy as Assessed by the Chinese Version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ-CIPN20)
The Chinese version of the EORTC QLQ-CIPN20 will be utilized to assess patient-reported chemotherapy-induced neuropathy. This 20-item questionnaire is an effective tool recommended by the National Cancer Institute for evaluating the CIPN phenotype, which includes sensory, motor, and autonomic symptoms in clinical trials. Both the Chinese and English versions demonstrate good internal consistency (Cronbach's α = 0.78-0.90), test-retest reliability (r = 0.73-0.84), and responsiveness to change (Cohen's d = 0.42-1.42).
Measured: From enrollment to the end of treatment at Week 12.

Secondary outcomes (5)

Clinician-Reported Chemotherapy-Induced Neuropathy as Assessed by the Total Neuropathy Score-Nurse (TNSn)
The TNSn will be used. This tool includes three symptom-related questions that evaluate sensory symptom distribution, motor symptom impact, and autonomic symptom presence, along with assessments of vibration and pinprick sensations. Each symptom and sign is rated on a scale from 0 to 4, with higher scores indicating more severe conditions. The TNSn has been validated in clinimetric studies, showing a Minimal Clinically Important Difference of 2.79 points.
Measured: At baseline (before intervention), Week 6, and Week 12 after randomization.
General Symptoms as Assessed by the Symptom Distress Scale (SDS)
The SDS will be used to assess general symptoms, including nausea, loss of appetite, insomnia, pain, fatigue, constipation and diarrhea, concentration difficulties, and changes in physical appearance. The scale employs a 5-point Likert-type scoring system, where 1 indicates normal symptom levels and 5 represents the highest degree of distress. Total scores range from 10 to 50, with higher scores reflecting greater symptom distress. Previous studies have shown that the SDS has acceptable internal consistency, with Cronbach's α values between 0.71 and 0.88.
Measured: At baseline (before intervention), Week 6, and Week 12 after randomization.
Timed Up and Go Test
The TUGT measures dynamic balance and mobility by timing how long it takes a participant to rise from a seated position, walk three meters, turn around, walk back, and sit down. Participants will perform the task twice, and the average time will be recorded.
Measured: At baseline (before intervention), Week 6, and Week 12 after randomization.
6-Minute Walk Test
The 6MWT evaluates endurance and physical performance by measuring the distance participants can walk at their usual speed for six minutes along a flat corridor, with the total distance recorded in meters. This test quantitatively reflects functional performance and exercise capacity, making it relevant for this population.
Measured: At baseline (before intervention), Week 6, and Week 12 after randomization.
Health-Related Quality of Life as Assessed by the Chinese Version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
The EORTC QLQ-C30 will be used to assess health-related quality of life. Previous studies indicate moderate to good test-retest reliability (r = 0.54-0.86) and person separation reliability (r = 0.47-0.89) for both the English and Chinese versions.
Measured: At baseline (before intervention), Week 6, and Week 12 after randomization.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Dec 202620 Dec 2028

First posted16 Oct 2026
Study start21 Dec 2026 (estimated)
Primary completion20 Dec 2028 (estimated)
Study completion20 Dec 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (40)Papers the sponsor has linked to this study.
Other trials for Chemotherapy-induced NeuropathyStudies of the same condition, open and under way.
More trials run by The Hong Kong Polytechnic UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 60 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07877558
Sponsor's protocol ID: 23241001
Other IDs: 23241001
Acronym: CIN
Status last verified: Sep 2026
First submitted: 4 Oct 2026
Last updated: 16 Oct 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: All individual participant data underlying the results reported in the publication will be made available.

Publications

Hurst H, Bolton J. Assessing the clinical significance of change scores recorded on subjective outcome measures. J Manipulative Physiol Ther. 2004 Jan;27(1):26-35. doi: 10.1016/j.jmpt.2003.11.003.
PubMed 14739871
Shih CL, Chen CH, Sheu CF, Lang HC, Hsieh CL. Validating and improving the reliability of the EORTC qlq-c30 using a multidimensional Rasch model. Value Health. 2013 Jul-Aug;16(5):848-54. doi: 10.1016/j.jval.2013.05.004. Epub 2013 Jul 17.
PubMed 23947980
McCrary JM, Goldstein D, Wyld D, Henderson R, Lewis CR, Park SB. Mobility in survivors with chemotherapy-induced peripheral neuropathy and utility of the 6-min walk test. J Cancer Surviv. 2019 Aug;13(4):495-502. doi: 10.1007/s11764-019-00769-7. Epub 2019 Jun 6.
PubMed 31172429
Winters-Stone KM, Krasnow SM, Horak FB, Mancini M, Cameron MH, Dieckmann NF, Stoyles SA, Roeland EJ. Identifying trajectories and predictors of chemotherapy-induced peripheral neuropathy symptoms, physical functioning, and falls across treatment and recovery in adults treated with neurotoxic chemotherapy: the PATTERN observational study protocol (NCT05790538). BMC Cancer. 2023 Nov 10;23(1):1087. doi: 10.1186/s12885-023-11546-2.
PubMed 37946117
Stapleton SJ, Holden J, Epstein J, Wilkie DJ. A Systematic Review of the Symptom Distress Scale in Advanced Cancer Studies. Cancer Nurs. 2016 Jul-Aug;39(4):E9-E23. doi: 10.1097/NCC.0000000000000292.
PubMed 26252436
Alberti P, Bernasconi DP, Cornblath DR, Merkies ISJ, Park SB, Velasco R, Bruna J, Psimaras D, Koeppen S, Pace A, Dorsey SG, Argyriou AA, Kalofonos HP, Briani C, Schenone A, Faber CG, Mazzeo A, Grisold W, Valsecchi M, Cavaletti G; CI-PeriNomS group. Prospective Evaluation of Health Care Provider and Patient Assessments in Chemotherapy-Induced Peripheral Neurotoxicity. Neurology. 2021 Aug 17;97(7):e660-e672. doi: 10.1212/WNL.0000000000012300. Epub 2021 Jun 2.
PubMed 34078718
Cheng HL, Molassiotis A. Longitudinal validation and comparison of the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life-Chemotherapy-Induced Peripheral Neuropathy Questionnaire (EORTC QLQ-CIPN20) and the Functional Assessment of Cancer-Gynecologic Oncology Group-Neurotoxicity subscale (FACT/GOG-Ntx). Asia Pac J Clin Oncol. 2019 Feb;15(1):56-62. doi: 10.1111/ajco.13000. Epub 2018 Jun 5.
PubMed 29873180
Dorsey SG, Kleckner IR, Barton D, Mustian K, O'Mara A, St Germain D, Cavaletti G, Danhauer SC, Hershman DL, Hohmann AG, Hoke A, Hopkins JO, Kelly KP, Loprinzi CL, McLeod HL, Mohile S, Paice J, Rowland JH, Salvemini D, Segal RA, Smith EL, Stevens WM, Janelsins MC. The National Cancer Institute Clinical Trials Planning Meeting for Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy. J Natl Cancer Inst. 2019 Jun 1;111(6):531-537. doi: 10.1093/jnci/djz011.
PubMed 30715378
Cocks K, Torgerson DJ. Sample size calculations for pilot randomized trials: a confidence interval approach. J Clin Epidemiol. 2013 Feb;66(2):197-201. doi: 10.1016/j.jclinepi.2012.09.002. Epub 2012 Nov 27.
PubMed 23195919
Pan L, Wang J, Wu W, Wang Y, Zhu Y, Song Y. Transcutaneous auricular vagus nerve stimulation improves working memory in temporal lobe epilepsy: A randomized double-blind study. CNS Neurosci Ther. 2024 Feb;30(2):e14395. doi: 10.1111/cns.14395. Epub 2023 Aug 8.
PubMed 37553557
Steidel K, Krause K, Menzler K, Strzelczyk A, Immisch I, Fuest S, Gorny I, Mross P, Hakel L, Schmidt L, Timmermann L, Rosenow F, Bauer S, Knake S. Transcutaneous auricular vagus nerve stimulation influences gastric motility: A randomized, double-blind trial in healthy individuals. Brain Stimul. 2021 Sep-Oct;14(5):1126-1132. doi: 10.1016/j.brs.2021.06.006. Epub 2021 Jun 27.
PubMed 34187756
Bauer S, Baier H, Baumgartner C, Bohlmann K, Fauser S, Graf W, Hillenbrand B, Hirsch M, Last C, Lerche H, Mayer T, Schulze-Bonhage A, Steinhoff BJ, Weber Y, Hartlep A, Rosenow F, Hamer HM. Transcutaneous Vagus Nerve Stimulation (tVNS) for Treatment of Drug-Resistant Epilepsy: A Randomized, Double-Blind Clinical Trial (cMPsE02). Brain Stimul. 2016 May-Jun;9(3):356-363. doi: 10.1016/j.brs.2015.11.003. Epub 2016 Jan 20.
PubMed 27033012
Zhang J, Chen Q, Shen Q, Yan C, Jiang T, Li J, Sayer S, Ai Z, Yu X, Zeng Q, Chen G. Effectiveness of Transcutaneous Auricular Vagal Nerve Stimulation on Alleviating Postoperative Pain Following Thoracoscopic Lobectomy: A Participant- and Assessor-blinded, Randomized Controlled Trial. Clin J Pain. 2025 Oct 1;41(10):e1315. doi: 10.1097/AJP.0000000000001315.
PubMed 40775700
Pudkasam S, Feehan J, Talevski J, Vingrys K, Polman R, Chinlumprasert N, Stojanovska L, Apostolopoulos V. Motivational strategies to improve adherence to physical activity in breast cancer survivors: A systematic review and meta-analysis. Maturitas. 2021 Oct;152:32-47. doi: 10.1016/j.maturitas.2021.06.008. Epub 2021 Jun 24.
PubMed 34674806
Nishijima TF, Shimokawa M, Hamabe T, Komoda M, Okumura Y, Arimizu K, Morita M, Esaki T, Nyrop KA. Development of a Leg And Walking Self-exercise (LAWS) program for older adults during cancer treatment. Support Care Cancer. 2024 Nov 5;32(12):773. doi: 10.1007/s00520-024-08965-7.
PubMed 39499396

Interested in taking part?

Mian Wang, PhD

Hong Kong SAR, +852 6879 9254

robbie-m.wang@polyu.edu.hk

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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NeuroGuard: Psilocybin Trial for Preventing Chemo-induced Neuropathy
Psilocybin, Neuropathy
RecruitingObservational study
Relationship Between Great Toe Strength And Symptoms of Chemotherapy-Induced Peripheral Neuropathy (CIPN)
Chemotherapy-induced Peripheral Neuropathy (CIPN), Healthy
RecruitingEarly Phase 1
Neuroprotective Potential of Cannabidiol (CBD) in Preventing Oxaliplatin (Ox)-Induced Neuropathy
Oxaliplatin Induced Peripheral Neuropathy in Cancer Patients, Metastatic Colorectal Cancer (CRC)

All Chemotherapy-induced Neuropathy trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Combining Home-Based Exercise and Non-Invasive Vagus Nerve Stimulation to Enhance Rehabilitation for Cancer Survivors With Chemotherapy-Induced Neuropathy: A Phase II Randomized Controlled Trial
ClinicalTrials.gov ID: NCT07877558
Acronym / sponsor ID: CIN / 23241001
Conditions: Chemotherapy-induced Neuropathy
Keywords: Chemotherapy-induced neuropathy, Exercise, Non-invasive vagus nerve stimulation, Cancer survivors, Phase II, Randomized controlled trial
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 60 participants (estimated)
Lead sponsor: The Hong Kong Polytechnic UniversityUniversity, hospital or other
Collaborators: Pamela Youde Nethersole Eastern Hospital, Kwong Wah Hospital, Tuen Mun Hospital
Study start: 21 Dec 2026 (estimated)
Primary completion: 20 Dec 2028 (estimated)
Study completion: 20 Dec 2028 (estimated)
First posted: 16 Oct 2026 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Interventions: Participants in the experimental groups will engage in a 12-week home-based exercise program, with the ERS group receiving real nVNS and the ESS group receiving sham stimulation.

Study design

Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Exercise with Real nVNS (ERS) group	Experimental	Device: Active non-invasive vagus nerve stimulation (nVNS), Behavioral: Home-based aerobic and resistance exercise programParticipants will receive active non-invasive vagus nerve stimulation (nVNS) concurrently with a standardized 12-week home-based exercise program after baseline assessment and randomization. The exercise program will include moderate-intensity aerobic walking (30 min daily; initial step goal based on pre-intervention average daily steps; weekly increase of 5-20%) and resistance training, targeting Borg 3-5/10. Active nVNS will be applied to the left cymba concha using tVNS501 at 25 Hz with a pulse width of 250 µs, 30 seconds on and 30 seconds off, and an intensity of 0.25-2.0 mA (maximum tolerable level) during exercise. It will be stopped during rest and after exercise.
Exercise with Sham nVNS (ESS) group	Sham comparator	Device: Sham non-invasive vagus nerve stimulation (nVNS), Behavioral: Home-based aerobic and resistance exercise programThe ESS group will receive the same 12-week home-based exercise program as the ERS group following baseline assessment and randomization, including moderate-intensity aerobic walking and resistance training. However, the stimulator will deliver a low frequency of 1 Hz at an intensity that elicits only the minimum perceptible sensation, with the aim of inducing a subtherapeutic placebo effect by mimicking active stimulation. Sham stimulation will be administered by the same research associate during the first face-to-face training session, after which participants will self-administer it concurrently with the home-based exercise program.
Usual Care (UC) group	No intervention	–The UC group will receive routine follow-up and consultation with doctors and/or nurses, without any supplementary information regarding home-based exercise or nVNS during the study period. However, they will have the opportunity to access the home-based exercise program, including a face-to-face session and an instruction booklet containing information regarding only the home-based exercise program, but not nVNS stimulator operation, after completing the final post-intervention assessment at Week 12.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Hong Kong residents who can communicate in Cantonese, Mandarin, or English;
Aged 18 years or older;
Cancer survivors with complete disease remission after radical treatment;
Completed a chemotherapy regimen with radical intent that included at least one of the following agents for a minimum of 3 months:
Have CIN of at least grade 2 assessed by a clinician based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE 5.0), or self-rate ≥ 2 points on at least one item in the 4-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire;

Key exclusion criteria (13 listed)

Known history of peripheral neuropathy or related symptoms prior to chemotherapy;
History of heart disease;
Bradycardia (heart rate < 60 beats per minute);
Pregnancy;
Presence of active implants, such as cardiac pacemakers, cochlear implants, and implanted neurostimulators;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Active non-invasive vagus nerve stimulation (nVNS)nVNS will be applied to the left auricular region during the 12-week home-based exercise program. The ERS group will receive real stimulation at a frequency of 25 Hz, a pulse width of 250 µs, a pulse-train duration of 30 seconds on and 30 seconds off, and an intensity set at the maximum tolerable level for each participant (0.25-2.0 mA). Stimulation will be stopped during rest and after exercise. A portable device (tVNS501; Changzhou Rishena Medical Device Co., Ltd., Jiangsu, China) will be used to deliver the stimulation. During the first face-to-face training session, a trained research associate will configure the device parameters and position the electrode on the participant's left cymba concha. Subsequently, participants will be trained to self-administer the stimulation during home-based exercise.	Device	Exercise with Real nVNS (ERS) group
Sham non-invasive vagus nerve stimulation (nVNS)The ESS group will undergo sham stimulation using the same device and electrode placement as the ERS group. Sham stimulation will be administered by the same trained research associate during the first face-to-face training session and subsequently self-administered by the participants during the 12-week home-based exercise program. However, the stimulator will be set to deliver a low stimulation frequency of 1 Hz at an intensity that elicits only the minimum perceptible sensation, with the aim of inducing a subtherapeutic placebo effect by mimicking active stimulation. The pulse width will be set to the lowest output of the stimulator, 100 µs, and the pulse-train duration will be 10 seconds on and 50 seconds off, thereby minimizing any potential physiological effects.	Device	Exercise with Sham nVNS (ESS) group
Home-based aerobic and resistance exercise programThe home-based exercise program includes aerobic and resistance training at moderate intensity (modified Borg 3-5/10). Aerobic: daily walking 30 min, initial step goal based on pre-intervention average daily steps, increased by 5-20% each week for 12 weeks, with self-monitoring of Borg and weekly follow-up guidance. Resistance: upper- and lower-body elastic band exercises (shoulder flexion/extension, horizontal abduction, elbow flexion/extension, heel raises, partial squats), 1-2 sets of 6 repetitions per set, completed within 1 minute, with 1-1.5 minutes of rest between sets, for a total of up to 30 minutes, progressing to a maximum of 15 repetitions per set. Participants receive an instruction booklet, three elastic bands, and a wrist pedometer. A 60-min face-to-face training session is delivered by a trained research associate at a study hospital, a university teaching room, or the participant's home.	Behavioural	Exercise with Real nVNS (ERS) group, Exercise with Sham nVNS (ESS) group

Primary outcome

Patient-Reported Chemotherapy-Induced Neuropathy as Assessed by the Chinese Version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ-CIPN20)
Time frame: From enrollment to the end of treatment at Week 12.
The Chinese version of the EORTC QLQ-CIPN20 will be utilized to assess patient-reported chemotherapy-induced neuropathy. This 20-item questionnaire is an effective tool recommended by the National Cancer Institute for evaluating the CIPN phenotype, which includes sensory, motor, and autonomic symptoms in clinical trials. Both the Chinese and English versions demonstrate good internal consistency (Cronbach's α = 0.78-0.90), test-retest reliability (r = 0.73-0.84), and responsiveness to change (Cohen's d = 0.42-1.42).

5 secondary outcomes

Clinician-Reported Chemotherapy-Induced Neuropathy as Assessed by the Total Neuropathy Score-Nurse (TNSn)
Time frame: At baseline (before intervention), Week 6, and Week 12 after randomization.
General Symptoms as Assessed by the Symptom Distress Scale (SDS)
Time frame: At baseline (before intervention), Week 6, and Week 12 after randomization.
Timed Up and Go Test
Time frame: At baseline (before intervention), Week 6, and Week 12 after randomization.
6-Minute Walk Test
Time frame: At baseline (before intervention), Week 6, and Week 12 after randomization.
Health-Related Quality of Life as Assessed by the Chinese Version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
Time frame: At baseline (before intervention), Week 6, and Week 12 after randomization.

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
Background: PubMed 14739871Hurst H, Bolton J. Assessing the clinical significance of change scores recorded on subjective outcome measures. J Manipulative Physiol Ther. 2004 Jan;27(1):26-35. doi: 10.1016/j.jmpt.2003.11.003.
Background: PubMed 23947980Shih CL, Chen CH, Sheu CF, Lang HC, Hsieh CL. Validating and improving the reliability of the EORTC qlq-c30 using a multidimensional Rasch model. Value Health. 2013 Jul-Aug;16(5):848-54. doi: 10.1016/j.jval.2013.05.004. Epub 2013 Jul 17.
Background: PubMed 31172429McCrary JM, Goldstein D, Wyld D, Henderson R, Lewis CR, Park SB. Mobility in survivors with chemotherapy-induced peripheral neuropathy and utility of the 6-min walk test. J Cancer Surviv. 2019 Aug;13(4):495-502. doi: 10.1007/s11764-019-00769-7. Epub 2019 Jun 6.
Background: PubMed 37946117Winters-Stone KM, Krasnow SM, Horak FB, Mancini M, Cameron MH, Dieckmann NF, Stoyles SA, Roeland EJ. Identifying trajectories and predictors of chemotherapy-induced peripheral neuropathy symptoms, physical functioning, and falls across treatment and recovery in adults treated with neurotoxic chemotherapy: the PATTERN observational study protocol (NCT05790538). BMC Cancer. 2023 Nov 10;23(1):1087. doi: 10.1186/s12885-023-11546-2.
Background: PubMed 26252436Stapleton SJ, Holden J, Epstein J, Wilkie DJ. A Systematic Review of the Symptom Distress Scale in Advanced Cancer Studies. Cancer Nurs. 2016 Jul-Aug;39(4):E9-E23. doi: 10.1097/NCC.0000000000000292.
Background: PubMed 34078718Alberti P, Bernasconi DP, Cornblath DR, Merkies ISJ, Park SB, Velasco R, Bruna J, Psimaras D, Koeppen S, Pace A, Dorsey SG, Argyriou AA, Kalofonos HP, Briani C, Schenone A, Faber CG, Mazzeo A, Grisold W, Valsecchi M, Cavaletti G; CI-PeriNomS group. Prospective Evaluation of Health Care Provider and Patient Assessments in Chemotherapy-Induced Peripheral Neurotoxicity. Neurology. 2021 Aug 17;97(7):e660-e672. doi: 10.1212/WNL.0000000000012300. Epub 2021 Jun 2.
Background: PubMed 29873180Cheng HL, Molassiotis A. Longitudinal validation and comparison of the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life-Chemotherapy-Induced Peripheral Neuropathy Questionnaire (EORTC QLQ-CIPN20) and the Functional Assessment of Cancer-Gynecologic Oncology Group-Neurotoxicity subscale (FACT/GOG-Ntx). Asia Pac J Clin Oncol. 2019 Feb;15(1):56-62. doi: 10.1111/ajco.13000. Epub 2018 Jun 5.
Background: PubMed 30715378Dorsey SG, Kleckner IR, Barton D, Mustian K, O'Mara A, St Germain D, Cavaletti G, Danhauer SC, Hershman DL, Hohmann AG, Hoke A, Hopkins JO, Kelly KP, Loprinzi CL, McLeod HL, Mohile S, Paice J, Rowland JH, Salvemini D, Segal RA, Smith EL, Stevens WM, Janelsins MC. The National Cancer Institute Clinical Trials Planning Meeting for Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy. J Natl Cancer Inst. 2019 Jun 1;111(6):531-537. doi: 10.1093/jnci/djz011.
Background: PubMed 23195919Cocks K, Torgerson DJ. Sample size calculations for pilot randomized trials: a confidence interval approach. J Clin Epidemiol. 2013 Feb;66(2):197-201. doi: 10.1016/j.jclinepi.2012.09.002. Epub 2012 Nov 27.
Background: PubMed 37553557Pan L, Wang J, Wu W, Wang Y, Zhu Y, Song Y. Transcutaneous auricular vagus nerve stimulation improves working memory in temporal lobe epilepsy: A randomized double-blind study. CNS Neurosci Ther. 2024 Feb;30(2):e14395. doi: 10.1111/cns.14395. Epub 2023 Aug 8.
Background: PubMed 34187756Steidel K, Krause K, Menzler K, Strzelczyk A, Immisch I, Fuest S, Gorny I, Mross P, Hakel L, Schmidt L, Timmermann L, Rosenow F, Bauer S, Knake S. Transcutaneous auricular vagus nerve stimulation influences gastric motility: A randomized, double-blind trial in healthy individuals. Brain Stimul. 2021 Sep-Oct;14(5):1126-1132. doi: 10.1016/j.brs.2021.06.006. Epub 2021 Jun 27.
Background: PubMed 27033012Bauer S, Baier H, Baumgartner C, Bohlmann K, Fauser S, Graf W, Hillenbrand B, Hirsch M, Last C, Lerche H, Mayer T, Schulze-Bonhage A, Steinhoff BJ, Weber Y, Hartlep A, Rosenow F, Hamer HM. Transcutaneous Vagus Nerve Stimulation (tVNS) for Treatment of Drug-Resistant Epilepsy: A Randomized, Double-Blind Clinical Trial (cMPsE02). Brain Stimul. 2016 May-Jun;9(3):356-363. doi: 10.1016/j.brs.2015.11.003. Epub 2016 Jan 20.
Individual participant dataSharing planned: Yes. All individual participant data underlying the results reported in the publication will be made available.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Mian Wang, PhD contact

Hong Kong SAR, +852 6879 9254

robbie-m.wang@polyu.edu.hk

Fenglin Zhang, MPhil contact

Hong Kong SAR, +852 7018 5728

reyna.zhang@polyu.edu.hk

Mian Wang, PhD principal investigator

The Hong Kong Polytechnic University

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Mian Wang, PhD (Hong Kong SAR, +852 6879 9254, robbie-m.wang@polyu.edu.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Patient-Reported Chemotherapy-Induced Neuropathy as Assessed by the Chinese Version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ-CIPN20) (time frame: From enrollment to the end of treatment at Week 12.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07877558, which also lists 40 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.