Neuromodulation for Pulmonary Arterial Hypertension

(NIP Trial)

Overseen By Tarun Dasari, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Oklahoma

Disqualifiers: Inability to walk, wheelchair-bound, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a gentle nerve stimulation technique can aid individuals with pulmonary arterial hypertension, a type of high blood pressure affecting the lungs. Researchers aim to determine if daily low-level tragus stimulation (a small area on the ear) can enhance walking distance, heart function, and certain blood markers. Participants will receive either the actual treatment or a placebo for four weeks. This trial suits individuals diagnosed with Group 1 pulmonary hypertension who can walk and experience moderate symptoms. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that low-level tragus stimulation is safe for patients with pulmonary hypertension?

Research has shown that low-level tragus stimulation (LLTS) is generally safe. Studies have found that it can lower blood pressure in young adults with hypertension without causing major problems, indicating that LLTS has been well-tolerated in past research.

In these studies, LLTS also demonstrated potential for protecting the heart, which is promising for conditions like pulmonary hypertension. However, while early results are encouraging, more research is needed to confirm its long-term safety and effectiveness.

For those considering joining a trial, it's important to know that past studies have not linked LLTS to serious side effects. The current trial is in its early stages, with a strong focus on safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary hypertension?

Researchers are excited about low-level tragus stimulation (LLTS) for pulmonary arterial hypertension because it offers a novel approach by modulating the autonomic nervous system. Unlike current treatments that primarily focus on dilating blood vessels, LLTS targets the vagus nerve to potentially reduce inflammation and improve heart function. This non-invasive technique involves simple daily stimulation of the tragus, a part of the outer ear, which could lead to fewer side effects and a more convenient treatment regimen compared to traditional medications. The placebo arm provides a critical comparison to validate LLTS's effectiveness, as it involves stimulation of a non-innervated ear area, ensuring any observed benefits are due to the specific nerve-targeted approach.

What evidence suggests that low-level tragus stimulation is effective for pulmonary hypertension?

This trial will compare low-level tragus stimulation with a placebo treatment for pulmonary arterial hypertension. Research has shown that gently stimulating the tragus, a small part of the ear, might help lower blood pressure. In studies with young adults who have high blood pressure, this method led to noticeable reductions. Some research also suggests that this technique could improve heart health by affecting the body's nervous system. These benefits might occur because it changes the balance of certain chemicals and nerve signals in the body. While more research is needed, early results suggest this could be a promising treatment for heart-related issues. ^{1 2 3 5 6}

Who Is on the Research Team?

Tarun Dasari, MD

Principal Investigator

University of Oklahoma

Are You a Good Fit for This Trial?

This trial is for patients with Group 1 pulmonary hypertension. Participants should be able to undergo daily low-level tragus stimulation and return after 4 weeks for follow-up tests, including a walking test, vascular function assessment, and heart function evaluation via echocardiography.

Exclusion Criteria

I can walk and am not wheelchair-bound or expecting to live less than 3 to 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Baseline tests including 6-minute walk distance, vascular function testing, blood samples, and echocardiography

1 day

1 visit (in-person)

Treatment

Participants undergo low-level tragus stimulation for 1 hour every day for 4 weeks

4 weeks

Daily self-administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including repeat tests

1 day

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Low-level tragus stimulation

Trial Overview The study is testing if low-level tragus stimulation (neuromodulation) can improve blood vessel function, exercise capacity measured by a walking test, and certain blood markers in patients with pulmonary hypertension over a period of 4 weeks.

How Is the Trial Designed?

Group I: LLTS arm Experimental Treatment 1 Intervention

Patients in this group will undergo low-level tragus stimulation for 1 hour every day for 4 weeks.

Group II: Placebo arm Placebo Group 1 Intervention

Patient will undergo stimulation but on the ear lobule which is devoid of any vagus nerve innervation. This will be used as a sham comparison group.

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.032269

Low‐Level Tragus Stimulation Attenuates Blood Pressure ... LL‐TS led to significant blood pressure reductions in young patients with essential hypertension. Further larger trials are needed to confirm ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39868455

Low-level tragus stimulation as a treatment for primary ... LL-TS triggering a complex systemic response may offer a broader cardioprotective potential than expected as a recent investigation outlined blood pressure [BP ...

3. journals.physiology.org journals.physiology.org/doi/full/10.1152/jn.00575.2024?doi=10.1152/jn.00575.2024

Low-level tragus stimulation as a treatment for primary ... LL-TS shows potential as a safe, nondrug option for lowering BP in young adults with hypertension and may also offer a broader cardioprotective potential apart ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2405500X23002943

Insights Into the Effects of Low-Level Vagus Nerve ... Low-level vagus nerve stimulation through the tragus (tLLVNS) is increasingly acknowledged as a therapeutic strategy to prevent and treat atrial fibrillation.

5. heartrhythmopen.com heartrhythmopen.com/article/S2666-5018(22)00350-6/fulltext

Low-level tragus stimulation improves autoantibody ... LLTS suppressed the postural tachycardia, improved the sympathovagal balance with increased acetylcholine secretion, and attenuated the ...

6. withpower.com withpower.com/clinical-trials/for-hypertension

Top Hypertension Clinical Trials | Power Investigators hypothesized that low-level tragus stimulation (neuromodulation) will lead to improvement in vascular function, 6-minute walk distance and blood ...