Alleviating Dyspnea With Non-Invasive Neuromodulation

NCT06985628 | Completed FDA Device

• 1 other identifier: 2025-5604
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this feasibility sham-controlled randomized trial is to assess the feasibility of studying non-invasive neuromodulation techniques, specifically transcutaneous vagal nerve stimulation (tVNS) and transcutaneous electrical nerve stimulation (TENS) of the trigeminal nerve to alleviate dyspnea in patients with chronic pulmonary disease. The main question it aims to answer is: Despite challenges in dyspnea generation and measurement, could non-invasive neuromodulation be reliably studied in chronic obstructive pulmonary disease (COPD) with severe dyspnea? Researchers will compare tVNS and trigeminal TENS to a sham (where the device is applied, but without stimulation) in order to see if non-invasive neuromodulation could relieve dyspnea. At the time of rehabilitation pre-assessment, participants routinely undergo a baseline maximal Cardiopulmonary Exercise Testing (CPET) on ergocycle to measure VO2max with repetitive assessments of the Borg scale and continuous monitoring of vital signs (oxygen saturation, heart rate, blood pressure, respiratory rate) throughout the test. Spirometry and symptom questionnaires (CAT score) are also routinely measured. In two dedicated study visits conducted 2 weeks apart from each other, n=8 participants will perform a submaximal constant workrate (CRW) at 80% workload of the VO2 max, either with cervical tVNS (n=4) or trigeminal TENS (n=4). In a cross-over design, both patient groups will undergo sham and active treatment of the neuromodulation technique in a randomly assigned number.

Conditions

Dyspnea; Chronic Obstructive Pulmonary Disease Severe

Keywords

Dyspnea; Breathlessness; Neuromodulation; Transcutaneous electrical nerve stimulation (TENS); Vagal nerve stimulation (VNS); Trigeminal nerve; Chronic obstructive pulmonary disease (COPD); Cardiopulmonary exercise test (CPET)

Outcome Measures

Primary Outcomes (1)

• Sample study completion proportion

  Percentage of recruited patients attending all visits and completing all tests

  At every visit until the visit 2 (at week 2)

Secondary Outcomes (7)

• General acceptability of the study procedures (exercise testing and interventions)

  At the end of the visit 2 (at week 2)

• Recruitment results

  At the visit 1 (at week 0)

• Adverse effects and undesirable events regarding the study procedures (exercise testing and interventions)

  At every visit until the visit 2 (at week 2)

• Occurrence of any adverse effects and undesirable events

  At every visit until the visit 2 (at week 2)

• Change from baseline for each intervention (tVNS and trigeminal TENS)

  At every visit until the visit 2 (at week 2)

Study Arms (2)

tVNS

EXPERIMENTAL

Two options of schedule (according to crossover randomization): \- VNSsa : Visit 1 : sham → Visit 2 : active tVNS \- VNSac : Visit 1 : active tVNS → Visit 2 : sham

Device: Transcutaneous vagal nerve stimulation (tVNS)

Trigeminal TENS

EXPERIMENTAL

Two options of schedule (according to crossover randomization): \- TENSsa : Visit 1 : sham → Visit 2 : active trigeminal TENS \- TENSac : Visit 1 : active trigeminal TENS → Visit 2 : sham

Device: Transcutaneous electrical nerve stimulation (TENS)

Interventions

Transcutaneous vagal nerve stimulation (tVNS) DEVICE

tVNS will be applied at the cervical level of the vagal nerve.

Also known as: gammaCore

tVNS

Transcutaneous electrical nerve stimulation (TENS) DEVICE

TENS will be applied facially on the trigeminal nerve.

Trigeminal TENS

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Severe COPD (between FEV1 20-50%, FEV1/FVC \< 0.7, and smoking history of ≥ 10 pack-years, 3rd-4th grade on the dyspnea scale modified Medical Research Council (mMRC), COPD Assessment Test (CAT) score ≥ 10)
• Significant chronic dyspnea for at least 6 months
• Referred for pulmonary rehabilitation
• Physical capability to undergo submaximal constant work rate (CRW)
• Ability to comprehend the implications of the procedures and follow-up visits and provide free informed consent

You may not qualify if:

• Presence of concurrent pulmonary restrictive features
• Neurological disorders susceptible to be influenced by neurostimulation procedures, including epilepsy, Parkinson's disease, trigeminal neuralgia, dysautonomia, and vagal disorders
• Unstable arrhythmias, and other cardiac instabilities
• Patients with cardiac pacemakers, defibrillators, or other metal implants
• Patients who have undergone pulmonary resection resulting in the absence of pulmonary lobe(s) or complete lung
• Other serious dyspneic conditions, such as anemia, heart failure with decreased ejection fraction, or mitochondrial dysfunction
• Pregnancy
• Active infections
• Known reactions or intolerance to tVNS or trigeminal TENS
• Patients must have no moderate-to-severe exacerbations (defined as an increase in symptoms for more than 3 days requiring corticosteroids or antibiotics, or hospitalisation) for at least one month before the baseline visit and at least one month before the first experimental visit (W0 visit). Participants that were randomized yet experience an exacerbation between the first (at week 0) and second (at week 2) experimental visits will be removed from the trial.
• \*Abbreviations : COPD : chronic obstructive pulmonary disease FEV1 : Forced Expiratory Volume in one second FVC : Forced vital capacity tVNS : Transcutaneous vagal nerve stimulation TENS : Transcutaneous electrical nerve stimulation

Sponsors & Collaborators

• Association Pulmonaire du Quebec: collaborator
• Québec Air-Intersectorialité-Respiratoire-Son network: collaborator
• Université de Sherbrooke: lead
• Fonds de la Recherche en Santé du Québec: collaborator

Study Sites (1)

Centre hospitalier universitaire de Sherbrooke (CHUS)

Sherbrooke, Quebec, J1H 5H3, Canada

Location

Related Publications (1)

• St-Pierre J, Mailhot-Larouche S, Garand G, Vezina FA, Leonard G, Iorio-Morin C, Couillard S. Non-invasive neuromodulation for alleviating dyspnoea: protocol for a feasibility sham-controlled randomised trial. BMJ Open. 2025 Jul 22;15(7):e103891. doi: 10.1136/bmjopen-2025-103891.

  PMID: 40701604 DERIVED

MeSH Terms

Conditions

Dyspnea; Pulmonary Disease, Chronic Obstructive

Interventions

Transcutaneous Electric Nerve Stimulation

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lung Diseases, Obstructive; Lung Diseases; Chronic Disease; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Physical Therapy Modalities; Rehabilitation; Analgesia; Anesthesia and Analgesia

Study Officials

• Joël St-Pierre, MD MSc candidate

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

• Simon Couillard, MD MSc

  Université de Sherbrooke

  STUDY DIRECTOR

• Christian Iorio-Morin, MD PhD

  Université de Sherbrooke

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This study employs a single-blinded format, where participants are unaware if they are receiving the sham or the real interventions, but the researchers in charge of data collection or of the analysis are not blinded.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D. M.Sc., Assistant-professor in medicine, Respirology Service, Department of Medicine

Model Details: At visit 1, participants will be randomized to one of four schedules for subsequent study procedures: VNSsa (visit 1 sham → visit 2 active), VNSac (visit 1 active → visit 2 sham), TENSsa (visit 1 sham → visit 2 active), or TENSac (visit 1 active → visit 2 sham) in a 1:1:1:1 ratio through the randomization function of REDCap. VNS : Vagal nerve stimulation TENS : Transcutaneous electrical nerve stimulation

Study Record Dates

• First Submitted: August 15, 2024
• First Posted: May 22, 2025
• Study Start: November 18, 2024
• Primary Completion: December 10, 2025
• Study Completion: December 10, 2025
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: Up to 2035
• Access Criteria: Data of this study may be shared if the investigators proposed use of the data has been approved by the study principal investigator and an institutional research ethics committee.

Locations

CA (1)