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

Overview

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.

Detailed description

This is a single-arm, open-label feasibility and expansion study evaluating transcutaneous vagus nerve stimulation (tVNS) as a supportive care intervention for immune-related fatigue in patients receiving immune checkpoint inhibitor therapy.

Eligible participants are adults with advanced or metastatic solid tumors who are currently receiving immune checkpoint inhibitors and experiencing clinically significant fatigue. Participants will self-administer tVNS at home once daily for 60 minutes over a 6-week intervention period using a non-invasive auricular stimulation device.

The primary objective is to evaluate feasibility, defined as adherence to the prescribed tVNS regimen. Secondary objectives include assessment of safety and tolerability, as well as changes in fatigue severity and health-related quality of life. Exploratory objectives include evaluation of changes in autonomic function, measured by heart rate variability, and inflammatory biomarkers obtained from blood samples.

Participants will complete study visits at baseline, Week 3, and Week 6, which include patient-reported outcome measures, adverse event assessments, and biospecimen collection. Heart rate variability will be continuously monitored using a wearable device throughout the intervention period.

This study is designed to generate feasibility and preliminary clinical and biological data to inform the design of future randomized trials evaluating tVNS as a treatment for immune-related fatigue.

Interventions

• 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
  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.

Primary outcome measures

• Feasibility of Daily tVNS Use [Time frame: Up to 6 weeks]

Secondary outcome measures (5)

• Safety and Tolerability of tVNS [Time frame: Up to 6 weeks]
• Change in Fatigue Severity (FACIT-F) [Time frame: Baseline to 6 weeks]
• Change in Health-Related Quality of Life (EORTC QLQ-C30) [Time frame: 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 [Time frame: Baseline to 6 weeks]
• Change in Inflammatory Biomarkers [Time frame: Baseline to 6 weeks]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Supportive care

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07529431 · STUDY00004152/UVMCC2603

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗