Feasibility of Noninvasive Trigeminal Nerve Stimulation During Exercise

Noninvasive Trigeminal Nerve Stimulation for Dyspnea: Mechanistic Characterization in Healthy Volunteers and Feasibility in COPD

The purpose of this study is to examine 1) effects of cutaneous electrical trigeminal nerve stimulation (eTNS) on respiratory control in healthy volunteers and 2) explore the potential of this approach to mitigate dyspnea in patients with chronic obstructive lung disease (COPD).

Study Overview

• Status: Not yet recruiting
• Conditions: COPD
• Intervention / Treatment: Procedure: Active Stimulation; Procedure: Sham Stimulation; Procedure: Fan therapy

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luu Pham, MD; Phone Number: 410-550-2118; Email: luu.pham@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Arm1 - Healthy Volunteers

Inclusion Criteria:

• Adults aged 18-50 years
• BMI 18-30 kg/m²
• Ability to provide informed consent and complete study procedures in English

Exclusion Criteria:

• Current daytime respiratory impairment such as uncontrolled asthma, uncontrolled COPD, pneumonia, or interstitial lung disease
• Use of supplemental oxygen
• Pregnancy or breastfeeding
• Current use of acetazolamide, Sodium-glucose cotransporter-2 (SGLT2) inhibitors, or daily opioids
• History of claustrophobia or panic disorder
• Metallic implants in the craniofacial or cervical region that may interfere with electrode placement or electrical stimulation
• Implanted cardiac or neuroelectric device (e.g., pacemaker, implantable cardioverter-defibrillator (ICD), deep brain stimulator, vagus nerve stimulator, implanted drug pump)
• Open, broken, inflamed, infected, or healing skin lesions at or near facial electrode placement sites
• Resting heart rate <60 Beats Per Minute
• History of seizure disorder or epilepsy

Arm 2 -COPD

Inclusion Criteria:

• Adults aged 40-75 years
• Confirmed diagnosis of COPD by spirometry (post-bronchodilator Forced Expiratory Volume (FEV1) /Forced Vital Capacity (FVC) <0.70) or provider documentation in medical records
• Modified Medical Research Council (mMRC) dyspnea grade ≥2
• Stable COPD (no exacerbation requiring hospitalization, systemic corticosteroids, or antibiotic therapy within the preceding 6 weeks)
• On stable COPD therapy for at least 4 weeks prior to enrollment
• Ability to provide informed consent and complete questionnaires in English
• Resting Peripheral Capillary Oxygen Saturation (SpO₂) ≥88% on room air or prescribed supplemental oxygen

Exclusion Criteria:

• Unstable cardiovascular disease (e.g., unstable angina, decompensated heart failure, recent MI within 6 months, uncontrolled arrhythmia) or peripheral vascular disease
• Patients with cardiovascular disease, including chest pain, heart failure, and aortic stenosis
• Resting heart rate <60 BPM
• Implanted cardiac or neuroelectric device (e.g., pacemaker, ICD, deep brain stimulator, vagus nerve stimulator, implanted drug pump)
• Metallic implants in the craniofacial or cervical region that may interfere with electrode placement or stimulation
• Open, broken, inflamed, infected, or healing skin lesions at or near facial electrode placement sites
• Active trigeminal neuralgia or other cranial neuropathy
• History of seizure disorder or epilepsy
• Severe or uncontrolled psychiatric disorder (e.g., psychosis, severe untreated anxiety or panic disorder) that would impair the ability to participate
• Pregnancy or breastfeeding
• COPD exacerbation requiring hospitalization, systemic corticosteroids, or antibiotics within the preceding 3 months
• Musculoskeletal pain, injury, or any other condition that precludes the use of a stationary bike for Cardiopulmonary Exercise Test (CPET)
• Any condition that, in the opinion of the investigator, would compromise participant safety or data integrity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Volunteers	Procedure: Active Stimulation; Active Non-Invasive Trigeminal Nerve Stimulation; Procedure: Sham Stimulation; Sham Stimulation
Experimental: Participants With COPD	Procedure: Active Stimulation; Active Non-Invasive Trigeminal Nerve Stimulation; Procedure: Sham Stimulation; Sham Stimulation; Procedure: Fan therapy; Handheld fan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with a >4 bpm decrease in heart rate	Trigeminal autonomic engagement. Proportion of participants with a >4 bpm decrease in heart rate during active eTNS compared to sham stimulation.	1 day
Proportion of enrolled participants who complete all randomized stimulation conditions	Protocol completion rate measured by proportion of enrolled participants who complete all randomized stimulation conditions.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minute Ventilation	Minute Ventilation	1 day
Dyspnea severity as assessed by the Borg CR10 scale	Borg CR10 score before and during stimulation. Scale range 0-10 higher score worse severity	1 day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in heart rate	changes in heart rate in response to stimulation	1 day
Change in heart rate variability	changes in heart rate variability in response to stimulation	1 day

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Center for Bioengineering Innovation and Design
• Investigators: Principal Investigator: Luu Pham, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: June 30, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: dyspnea; Control of breathing; neural stimulation
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Lung Diseases, Obstructive; Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Dyspnea
• Other Study ID Numbers: IRB00551380

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No