Clinical trial NCT06802380: Neuromodulation in Patients With Pulmonary Arterial Hypertension
Official title: Neuromodulation in Patients With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pulmonary Hypertension
Keywords: Neuromodulation
Endothelial function
6-minute walk distance
Right ventricular function
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
First posted: 2025-01-31
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized clinical study using low-level tragus stimulation compared to sham stimulation.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Investigators propose the following aims:

Aim 1: Quantitatively measure effects of LLTS on exercise capacity and quality of life in Pulmonary hypertension. A 6MWD and QoL (using Pulmonary hypertension questionnaire) will be performed at baseline and follow up (1 months).

Hypothesis 1: Short term LLTS would lead to improvement in exercise capacity and QoL.

Aim 2: Measure effect of neuromodulation on autonomic tone and inflammation. Heart rate variability (frequency and time domains) will be measured at baseline and after 1 months of LLTS. Serum will be used to analyze NT-Pro BNP, circulating inflammatory markers (IL-6,IL-18,TNF-a, IL1ra and CRP).

Hypothesis 2: Short term LLTS would lead to improvement in autonomic tone and inflammation.

Aim 3: Measure the effect of LLTS on endothelial function . Endothelial function (using ENDOPAT test) will be determined at baseline and at 1 months.

Results from this study will help investigators better understand PAH pathogenesis and provide investigators with further therapeutic targets and opportunities.

EXPERIMENTAL DESIGN:

For this application, investigators propose a prospective randomized double-blind study of LLTS vs. sham treatment.

Inclusion criteria: Patients older than 18 years of age, with pulmonary arterial hypertension (Group 1 PH) and WHO functional class II/III Exclusion:Patients with Inability to walk, wheelchair-bound, amputations, expected survival less than 3 to 6 months, active malignancy patients who are Spanish-speaking. would be excluded from the study.

PROPOSED PROCEDURE:

Patients with PAH would be screened from the Pulmonary Hypertension clinic located at OU Physicians building by the pulmonary hypertension facutly. Patients who meet inclusion criteria and consent to the study would be recruited.

Demographic data, medications used for PH, co-morbid conditions would be recorded. Patients would be escorted to the cardiovascular lab at the O-Donoghue building by the PH co-ordinator. EKG for heart rate variability, Six minute walk test, Endopat test for endothelial dysfunction would re recorded. The visit is expected to take close to 60 minutes.

Device administration and treatment protocol: Subjects will be trained on the day of enrollment to use PARASYM unit for self-administration of LLTS. Investigators will spend ample time explaining the nuances of the devices and provide time to subjects to familiarize with the device. Patients will be instructed to apply LLTS to the Tragus or ear lobe. Instruction manual and batteries will be provided.

In case of device malfunction, new devices will be provided to subjects within 48-72 hours (via mail or in person). Device parameters will be set to pulse width of 200 us and pulse frequency of 20 Hz. Amplitude will be titrated to level of sensory threshold (minimum 1 mA). The frequency and pulse width settings have been chosen based on our preliminary studies of LLTS in atrial fibrillation, diastolic HF and systolic HF. The final stimulation strength will be below the threshold (final output ³1mA) and subjects will be barely able to sense it. Patients will maintain a diary log for 4 weeks and perform stimulation for 1 hour daily (typically between 4-8pm, during the 2nd diurnal phase of high sympathetic tone). The time between 4-8 pm was selected for patient convenience as certain patients work hours may restrict use during the first diurnal phase in the morning. Sympathetic tone is highest during these diurnal phases, hence the rationale to target therapy during those times. The PARASYMTM device is also equipped with a treatment time recorder to get accurate logs of treatment. Patients will be asked to avoid caffeine for 4 hrs. and alcohol, smoking, and exercise for 12 h before the visit to avoid any interference with the functional tests that are performed

Eligibility criteria: Inclusion criteria: Patients older than 18 years of age, with pulmonary arterial hypertension (Group 1 PH) and WHO functional class II/III

Exclusion:Patients with Inability to walk, wheelchair-bound, amputations, expected survival less than 3 to 6 months, active malignancy patients who are Spanish-speaking. would be excluded from the study.

Primary outcomes:
measure: Heart rate variability
timeFrame: 4 weeks
Secondary outcomes:
measure: 6-minute walk distance
timeFrame: 4 weeks
Other outcomes:
measure: Right ventricular function
timeFrame: 4 weeks
measure: Endothelial oxidative stress
timeFrame: 4 weeks
Locations:
city: Oklahoma City
country: United States
facility: University of Oklahoma health sciences Center
state: Oklahoma
Study officials:
affiliation: University of Oklahoma
name: Tarun Dasari, MD
role: PRINCIPAL_INVESTIGATOR
References: