Feasibility and Expansion Trial of Transcutaneous Vagus Nerve Stimulation (tVNS) for Immune-Related Fatigue in Patients Receiving Immune Checkpoint Inhibitors

NCT07529431 | Not Yet Recruiting DMC

• 1 other identifier: STUDY00004152/UVMCC2603
• Study Type: interventional
• Target: 13
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study evaluates whether a non-invasive device called transcutaneous vagus nerve stimulation (tVNS) can be safely and feasibly used to help reduce fatigue in patients receiving immunotherapy for cancer. Fatigue is a common and often severe side effect of immune checkpoint inhibitors, and there are currently limited effective treatment options. In this study, participants will use a small device at home that delivers mild electrical stimulation to the ear for 60 minutes each day over a 6-week period. The study will assess whether patients are able to use the device as prescribed (feasibility), how well it is tolerated, and whether it may improve fatigue and quality of life. The study will also explore changes in biological markers of inflammation and measures of nervous system function to better understand how tVNS may work. The results of this study will help determine whether this approach should be tested in larger future trials.

Conditions

Cancer-related Fatigue

Keywords

Cancer-related fatigue; Vagus nerve stimulation

Outcome Measures

Primary Outcomes (1)

• Feasibility of Daily tVNS Use

  Feasibility will be assessed based on adherence to the prescribed tVNS regimen. Feasibility is defined as the proportion of participants who complete at least 80% of prescribed tVNS sessions over the 6-week intervention period, as measured by concordance between participant-reported use and device-recorded usage.

  Up to 6 weeks

Secondary Outcomes (5)

• Safety and Tolerability of tVNS

  Up to 6 weeks

• Change in Fatigue Severity (FACIT-F)

  Baseline to 6 weeks

• Change in Health-Related Quality of Life (EORTC QLQ-C30)

  Health-related quality of life will be assessed using the EORTC QLQ-C30 global health status scale. Changes from baseline to Week 6 will be evaluated.

• Change in Heart Rate Variability

  Baseline to 6 weeks

• Change in Inflammatory Biomarkers

  Baseline to 6 weeks

Study Arms (1)

Transcutaneous Vagus Nerve Stimulation (tVNS)

EXPERIMENTAL

Participants will self-administer transcutaneous vagus nerve stimulation (tVNS) at home using a non-invasive auricular stimulation device for 60 minutes per day over a 6-week period. Participants will continue standard cancer therapy, including immune checkpoint inhibitors, during the study. Study assessments will include adherence monitoring, adverse event evaluation, patient-reported outcomes, and collection of blood samples and physiologic data.

Device: Participants will self-administer transcutaneous vagus nerve stimulation (tVNS) at home using a non-invasive auricular stimulation device for 60 minutes per day over a 6-week period. Participants will

Interventions

Participants will self-administer transcutaneous vagus nerve stimulation (tVNS) at home using a non-invasive auricular stimulation device for 60 minutes per day over a 6-week period. Participants will DEVICE

Participants will self-administer transcutaneous vagus nerve stimulation (tVNS) at home using a non-invasive auricular stimulation device for 60 minutes per day over a 6-week period. Participants will continue standard cancer therapy, including immune checkpoint inhibitors, during the study. Study assessments will include adherence monitoring, adverse event evaluation, patient-reported outcomes, and collection of blood samples and physiologic data.

Transcutaneous Vagus Nerve Stimulation (tVNS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• Histologically confirmed advanced or metastatic solid tumor
• Receiving immune checkpoint inhibitor therapy and completed at least two cycles
• Clinically significant fatigue (FACIT-F score ≤ 34)
• ECOG performance status 0-2
• Life expectancy of at least 3 months
• Ability to provide informed consent
• Access to a smartphone or tablet

You may not qualify if:

• Current or planned chemotherapy, targeted therapy, or radiation during the 4-week intervention period.
• Have received targeted therapy in the last 2 weeks
• Have received chemotherapy or radiation therapy in the last 4 weeks
• Symptomatic brain metastases defined as active neurologic complaint (headache, blurry vision, neurologic deficits or other symptom requiring treatment with steroids)
• Long term steroid use \>10 mg prednisone equivalent daily
• Active autoimmune disease requiring systemic immunosuppression
• Implanted electronic medical devices (e.g., pacemakers, defibrillators)
• History of epilepsy or vagal hypersensitivity
• Known arrhythmia or bradycardia (Baseline HR \< 50 bpm)
• Open wounds or dermatologic issues at the stimulation site
• Pregnancy or breastfeeding
• Participation in other fatigue-focused intervention trials
• Severe uncontrolled psychiatric illness (PHQ-9 \>20)

Sponsors & Collaborators

• University of Vermont Medical Center: lead

Central Study Contacts

Rohit Singh, MD

CONTACT

1 (802) 656-2021; rohit.singh@uvmhealth.org

Randall F Holcombe, MD

CONTACT

1 (802) 656-2021; randall.holcombe@med.uvm.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 14, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2035
• Last Updated: April 14, 2026

Record last verified: 2026-04