Pulmonary HypertensionPhase 1/2NIPNCT06802380
Neuromodulation in Patients With Pulmonary Arterial Hypertension
A Phase 1/2 study testing Low-level tragus stimulation in people with Pulmonary Hypertension, run by University of Oklahoma at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Pulmonary Hypertension
- What is being tested?
- Low-level tragus stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2025to 31 Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of Oklahoma health sciences Center
Oklahoma City, Oklahoma, 73104
Tarun Dasari, 405-271-4742, tarun-dasari@ouhsc.edu
Tarun Dasari, MD
About this study
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.
Read the 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
- Conditions
- Pulmonary Hypertension
- Being tested
- Low-level tragus stimulation, Sham stimulation
- Keywords
- Neuromodulation, Endothelial function, 6-minute walk distance, Right ventricular function
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-level tragus stimulationDevice
Low-level tragus stimulation will recruit the fibers from the inner part of the tragus of the external ear and sent afferent signals through the greater auricular branch of the vagus nerve. Ultimately the stimulation is transmitted to the dorsal vagal complex and the brainstem thereby modulating the neuronal activity in the vehicle output. Sham stimulation will be performed by clipping the electrode to the ear lobule which will not relay any afferent signals through the greater auricular branch of the vagus nerve.
Sham stimulationDevice
In the sham stimulation the electrodes will be attached to the ear lobule which are devoid of any afferent nerves traveling to the greater auricular branch of the vagus nerve.
| Study group | Role | What they receive |
|---|---|---|
| LLTS arm | Experimental | Patients in this group will undergo low-level tragus stimulation for 1 hour every day for 4 weeks. Receives: Device: Low-level tragus stimulation |
| Placebo arm | Sham comparator | 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. Receives: Device: Sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart rate variability
Change in the heart rate variability metrics. These are reflective of the autonomic tone and the imbalance. Investigators hypothesized that using low-level tragus stimulation in patients with pulmonary hypertension the heart rate variability will be favorably affected using low-level tragus stimulation compared to sham stimulation.
Time domain metrics are usually measured using variation of the standard R-R interval on the EKG in milliseconds.
Measured: 4 weeks
Secondary outcomes (1)
6-minute walk distance
A 6-minute walk test will be performed and the distance walked in 6 minutes as measured in meters will be quantified. Investigators hypothesized that using low-level tragus stimulation 6-minute walk distance will improve in patients with pulmonary hypertension after using the device for 4 weeks. This is in comparison to sham stimulation.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2025
- Study start1 Sep 2025 (estimated)
- Primary completion1 Nov 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by University of OklahomaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized clinical study using low-level tragus stimulation compared to sham stimulation.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tarun Dasari, MD, Principal investigator, University of Oklahoma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06802380
- Sponsor's protocol ID
- 17677
- Other IDs
- 17677
- Acronym
- NIP
- Status last verified
- Aug 2025
- First submitted
- 6 Dec 2024
- Last updated
- 27 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuromodulation in Patients With Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT06802380
- Acronym / sponsor ID
- NIP / 17677
- Conditions
- Pulmonary Hypertension
- Keywords
- Neuromodulation, Endothelial function, 6-minute walk distance, Right ventricular function
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Study start
- 1 Sep 2025 (estimated)
- Primary completion
- 1 Nov 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 31 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized clinical study using low-level tragus stimulation compared to sham stimulation.
| Arm | Type | Receives |
|---|---|---|
| LLTS arm | Experimental | Device: Low-level tragus stimulationPatients in this group will undergo low-level tragus stimulation for 1 hour every day for 4 weeks. |
| Placebo arm | Sham comparator | Device: Sham stimulationPatient 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 may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-level tragus stimulationLow-level tragus stimulation will recruit the fibers from the inner part of the tragus of the external ear and sent afferent signals through the greater auricular branch of the vagus nerve. Ultimately the stimulation is transmitted to the dorsal vagal complex and the brainstem thereby modulating the neuronal activity in the vehicle output. Sham stimulation will be performed by clipping the electrode to the ear lobule which will not relay any afferent signals through the greater auricular branch of the vagus nerve. | Device | LLTS arm |
| Sham stimulationIn the sham stimulation the electrodes will be attached to the ear lobule which are devoid of any afferent nerves traveling to the greater auricular branch of the vagus nerve. | Device | Placebo arm |
Primary outcome
Heart rate variability
Time frame: 4 weeks
Change in the heart rate variability metrics. These are reflective of the autonomic tone and the imbalance. Investigators hypothesized that using low-level tragus stimulation in patients with pulmonary hypertension the heart rate variability will be favorably affected using low-level tragus stimulation compared to sham stimulation. Time domain metrics are usually measured using variation of the standard R-R interval on the EKG in milliseconds.
1 secondary outcome
6-minute walk distance
Time frame: 4 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2025.
- Individual participant dataSharing planned: Undecided
Related trials for Pulmonary Hypertension
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tarun Dasari, MD principal investigator
University of Oklahoma
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Low-level tragus stimulation in people with Pulmonary Hypertension, run by University of Oklahoma at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 27 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tarun Dasari, MD (4052714742, tarun-dasari@ouhsc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart rate variability (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2025.