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

50 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Low-level tragus stimulation for Pulmonary Arterial Hypertension?

Research on similar treatments, like vagus nerve stimulation (VNS), shows promise in treating pulmonary arterial hypertension by improving heart function and reducing blood pressure in the lungs. VNS has been effective in other heart-related conditions, suggesting that neuromodulation techniques could help manage this disease. ^{1 2 3 4 5}

Is neuromodulation, like vagus nerve stimulation, safe for humans?

Vagus nerve stimulation (VNS) has been used in other heart-related conditions and can have unwanted effects, but it is generally considered safe. However, there are concerns about potential unwanted effects in sensitive patients, so more research is needed to fully understand its safety in humans. ^{1 2 3 6 7}

How does low-level tragus stimulation differ from other treatments for pulmonary arterial hypertension?

Low-level tragus stimulation is unique because it involves neuromodulation, specifically targeting the vagus nerve to restore balance in the autonomic nervous system, which can help reduce pulmonary artery pressure and improve heart function. Unlike traditional drug treatments, this approach aims to address the underlying autonomic imbalance contributing to the disease. ^{1 2 3 8 9}

What is the purpose of this trial?

Patients with Group 1 pulmonary hypertension will be enrolled in this study. Investigators will test the hypothesis of low-level tragal stimulation in patients with pulmonary hypertension. The study will be conducted over 4 weeks and patients will undergo low-level tragus stimulation for 1 hour every day for 4 weeks. At baseline the following tests will be conducted-6-minute walk distance, vascular function testing using noninvasive device and blood samples will be collected. Patient will also undergo a limited echocardiography to assess right ventricular function. After 4 weeks of stimulation patients will come back to undergo these tests again. Investigators hypothesized that low-level tragus stimulation (neuromodulation) will lead to improvement in vascular function, 6-minute walk distance and blood based biomarkers in patients with pulmonary hypertension.

Research Team

Tarun Dasari, MD

Principal Investigator

University of Oklahoma

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

Electrical Vagal Nerve Stimulation Ameliorates Pulmonary Vascular Remodeling and Improves Survival in Rats With Severe Pulmonary Arterial Hypertension. [2020]

2. China pubmed.ncbi.nlm.nih.gov

[Advances in neuromodulation of pulmonary hypertension]. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Pulmonary arterial hypertension: the case for a bioelectronic treatment. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The Evolution of Pulmonary Artery Denervation for Treatment of Pulmonary Arterial Hypertension. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Increased sympathetic nerve activity in pulmonary artery hypertension. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Long-term treatment with sildenafil citrate in pulmonary arterial hypertension: the SUPER-2 study. [2017]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Update on the clinical utility of sildenafil in the treatment of pulmonary arterial hypertension. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Intrathecal fentanyl blockade of afferent neural feedback from skeletal muscle during exercise in heart failure patients: Influence on circulatory power and pulmonary vascular capacitance. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Current status of pulmonary artery denervation. [2022]