Systolic Heart FailureNCT05230732
Neuromodulation of Inflammation and Endothelial Function
A study testing neuromodulation device in people with Systolic Heart Failure, run by University of Oklahoma at 1 site in United States.
Trial summary
Heart failure with reduced ejection fraction (HFrEF) is a major cause of mortality in United States. Aging is a major risk factor for adverse outcomes associated with HFrEF, with majority of the patient's over the age of 50, continuing to experience symptoms, reduced exercise capacity and poor quality of life. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Systolic Heart Failure
- What is being tested?
- neuromodulation device
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 158 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2022to 27 Feb 2027
- Phase
- Interventional
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Systolic heart failure with EF < or equal to 50%.
Who cannot join
- patients in overt congestive heart failure / recent acute myocardial infarction (< 4 weeks) or Unstable angina
- Active malignancy
- unilateral or bilateral vagotomy
- pregnant patients
- End stage liver disease
- history of recurrent vasovagal syncope, Sick sinus syndrome with no pacemaker, 2nd or 3rd degree AV block.
- Significant hypotension (Blood pressure < 90 mm Hg) secondary to autonomic dysfunction
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, 1 recruiting
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73117
Juvaria Anum, 4052713480, juvaria-anum@ouhsc.edu
Brittany Karfonta, 4052713480, brittany-karfonta@ouhsc.edu
About this study
Official title: Neuromodulation of Inflammation and Endothelial Function to Treat Elderly Patients With Systolic Heart Failure
Heart failure with reduced ejection fraction (HFrEF) is a major cause of mortality in United States. Aging is a major risk factor for adverse outcomes associated with HFrEF, with majority of the patient's over the age of 50, continuing to experience symptoms, reduced exercise capacity and poor quality of life. We have previously demonstrated that low level transcutaneous electrical stimulation of the vagus nerve at the tragus (LLTS) suppresses inflammation in patients with atrial fibrillation and diastolic dysfunction and improved endothelial dysfunction in patients with chronic heart failure. The overall objective of this proposal is to examine the effects of LLTS on heart failure symptoms, exercise capacity and quality of life in patients with HFrEF and simultaneously determine the impact of LLTS on the suppression of inflammation and improvement in endothelial function. Our specific aims include: 1. To examine the medium term effect of intermittent (1 hour daily for 3 months) LLTS on exercise capacity and quality of life, related to sham stimulation, in patients with HFrEF, 2. To determine the effects of medium-term LLTS on sympathovagal/autonomic balance (assessed by heart rate variability) and systemic inflammation in patients with HFrEF and 3. To determine the effects of medium-term LLTS on endothelial function in patients with HFrEF. The proposed proof-of-concept human studies will provide the basis for the design of further human studies using LLTS among larger populations with HFrEF. In light of the increasing number of elderly patients who continue to experience HFrEF symptoms, recognized is a key point of interest in this funding mechanism, and the suboptimal success of the currently available treatment options to ameliorate the problems mentioned above, an alternative novel approach such as LLTS has the potential to impact clinical practice and improve health outcomes among the large number of patients. It is anticipated that these investigations will contribute to a broader understanding of the role of autonomic imbalance, inflammation and endothelial dysfunction in the pathogenesis of HFrEF and how its inhibition can be used to provide therapeutic effects. Moreover, it is anticipated that a better understanding of how modulation of autonomic tone, inflammation and endothelial function affects one of the hallmarks of HFrEF will lead to the development of normal nonpharmacological and pharmacological approaches to treat this disease.
Read the detailed description
Prospective randomized double-blind study of Lowlevel Tragus stimulation-LLTS vs. sham treatment.
We will require n=108 participants (54 in each group) to reach statistical significance and to account for potential drop-out (anticipated <5%, based on previous study in atrial fibrillation) from the study and 50 subjects below the age of 50 will be enrolled in the control group 2 for comparison purposes, for a total of 158 patients.
Aim 1:
Objective 1: measure the medium-term effects of LLTS on exercise capacity in subjects with HF - 6-minute walk distance (6MWD) will be performed at baseline and after 3 months of LLTS. Change in 6MWD from baseline to 3 months will be compared between experimental and sham groups. Duration of test: <10 minutes. A dedicated quite hallway exists in the translational geroscience laboratory which will enable performance of the test. Study will be performed by the research coordinator.
Objective 2: assess the effects of medium-term LLTS on quality of life in subjects with HF - quality of life will be determined using standard HF questionnaire (MLWHF score). This questionnaire will be administered at baseline and after 3 months. Duration of test: <15 minutes. Study will be administered by our research coordinator either on paper or tablet.
Aim2:
Objective 1: measure the effects of medium-term LLTS on sympathovagal balance in subjects with HF - Heart rate variability (HRV), a well-established, noninvasive measure of autonomic function, will be measured and analyzed via 10 min ECG using standard Labscribe and Kubios software. The amplitude and changes of the low (0.04-0.15Hz), high (0.15-0.4Hz) and the low frequency/high frequency ratio along with specific time domain variables (SDNN,SDANN,pNN50,rMSSD) will be determined to reflect autonomic imbalance.
Objective 2: assess the effects of medium-term LLTS stimulation on HF biomarkers, inflammation - using high sensitivity ELISA kits, NT-Pro BNP, sST2, Interleukins (6, 1), TNF-α, hsCRP will be assayed.
Aim 3:
Objective 1: assess the effects of medium-term LLTS on vascular endothelial function -Flow-mediated vasodilatation (FMD) will be used to assess %-change in brachial artery diameter upon the release of temporary 5-min blood flow occlusion to the extremity using ultrasonography (Phillips Affinity X70). This is a standard, validated technique to assess FMD. Average time to perform this study is ~20 minutes.
- Conditions
- Systolic Heart Failure
- Being tested
- neuromodulation device, SHAM
- Medical subject headings
- Heart Failure, Systolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
neuromodulation deviceDevice
Active LLTS will be performed by use of a neuromodulation device with electrodes attached to the tragus of the ear. Stimulator will be applied continuously for 1 hour daily for 12 weeks
SHAMDevice
Sham LLTS will be performed by use of a neuromodulation device with electrodes attached to the ear lobule. Stimulator will be applied continuously for 1 hour daily for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Active LLTS will be performed by use of a neuromodulation device with electrodes attached to the tragus of the ear. Stimulator will be applied continuously for 1 hour daily for 12 weeks. Receives: Device: neuromodulation device |
| Control arm | Sham comparator | Sham LLTS will be performed by use of a neuromodulation device with electrodes attached to the ear lobule. Stimulator will be applied continuously for 1 hour daily for 12 weeks. Receives: Device: SHAM |
What is being measured
The primary outcome is the main question the study is designed to answer.
6MWD
6 minute walk distance
Measured: Change in 6MWD after 12 weeks compared to baseline
Secondary outcomes (1)
QoL
Quality of life will be assessed using the Minnesota living with heart failure questionnaire
Measured: Change in QoL after 12 weeks compared to baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2022
- Study start1 Sep 2022
- Primary completion27 Feb 2027 (estimated)
- Study completion27 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systolic Heart FailureStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 158 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Tarun Dasari, MD, MPH, Principal investigator, University of Oklahoma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05230732
- Sponsor's protocol ID
- 14101
- Other IDs
- 5R21AG075639-02
- Status last verified
- Aug 2026
- First submitted
- 10 Jan 2022
- Last updated
- 11 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuromodulation of Inflammation and Endothelial Function to Treat Elderly Patients With Systolic Heart Failure
- ClinicalTrials.gov ID
- NCT05230732
- Acronym / sponsor ID
- 14101
- Conditions
- Systolic Heart Failure
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 158 participants (estimated)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 27 Feb 2027 (estimated)
- Study completion
- 27 Feb 2027 (estimated)
- First posted
- 9 Feb 2022 (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.
Heart failure with reduced ejection fraction (HFrEF) is a major cause of mortality in United States. Aging is a major risk factor for adverse outcomes associated with HFrEF, with majority of the patient's over the age of 50, continuing to experience symptoms, reduced exercise capacity and poor quality of life. We have previously demonstrated that low level transcutaneous electrical stimulation of the vagus nerve at the tragus (LLTS) suppresses inflammation in patients with atrial fibrillation and diastolic dysfunction and improved endothelial dysfunction in patients with chronic heart failure. The overall objective of this proposal is to examine the effects of LLTS on heart failure symptoms, exercise capacity and quality of life in patients with HFrEF and simultaneously determine the impact of LLTS on the suppression of inflammation and improvement in endothelial function. Our specific aims include: 1. To examine the medium term effect of intermittent (1 hour daily for 3 months) LLTS on exercise capacity and quality of life, related to sham stimulation, in patients with HFrEF, 2. To determine the effects of medium-term LLTS on sympathovagal/autonomic balance (assessed by heart rate variability) and systemic inflammation in patients with HFrEF and 3. To determine the effects of medium-term LLTS on endothelial function in patients with HFrEF. The proposed proof-of-concept human studies will provide the basis for the design of further human studies using LLTS among larger populations with HFrEF. In light of the increasing number of elderly patients who continue to experience HFrEF symptoms, recognized is a key point of interest in this funding mechanism, and the suboptimal success of the currently available treatment options to ameliorate the problems mentioned above, an alternative novel approach such as LLTS has the potential to impact clinical practice and improve health outcomes among the large number of patients. It is anticipated that these investigations will contribute to a broader understanding of the role of autonomic imbalance, inflammation and endothelial dysfunction in the pathogenesis of HFrEF and how its inhibition can be used to provide therapeutic effects. Moreover, it is anticipated that a better understanding of how modulation of autonomic tone, inflammation and endothelial function affects one of the hallmarks of HFrEF will lead to the development of normal nonpharmacological and pharmacological approaches to treat this disease.
Detailed description
Prospective randomized double-blind study of Lowlevel Tragus stimulation-LLTS vs. sham treatment.
We will require n=108 participants (54 in each group) to reach statistical significance and to account for potential drop-out (anticipated <5%, based on previous study in atrial fibrillation) from the study and 50 subjects below the age of 50 will be enrolled in the control group 2 for comparison purposes, for a total of 158 patients.
Aim 1:
Objective 1: measure the medium-term effects of LLTS on exercise capacity in subjects with HF - 6-minute walk distance (6MWD) will be performed at baseline and after 3 months of LLTS. Change in 6MWD from baseline to 3 months will be compared between experimental and sham groups. Duration of test: <10 minutes. A dedicated quite hallway exists in the translational geroscience laboratory which will enable performance of the test. Study will be performed by the research coordinator.
Objective 2: assess the effects of medium-term LLTS on quality of life in subjects with HF - quality of life will be determined using standard HF questionnaire (MLWHF score). This questionnaire will be administered at baseline and after 3 months. Duration of test: <15 minutes. Study will be administered by our research coordinator either on paper or tablet.
Aim2:
Objective 1: measure the effects of medium-term LLTS on sympathovagal balance in subjects with HF - Heart rate variability (HRV), a well-established, noninvasive measure of autonomic function, will be measured and analyzed via 10 min ECG using standard Labscribe and Kubios software. The amplitude and changes of the low (0.04-0.15Hz), high (0.15-0.4Hz) and the low frequency/high frequency ratio along with specific time domain variables (SDNN,SDANN,pNN50,rMSSD) will be determined to reflect autonomic imbalance.
Objective 2: assess the effects of medium-term LLTS stimulation on HF biomarkers, inflammation - using high sensitivity ELISA kits, NT-Pro BNP, sST2, Interleukins (6, 1), TNF-α, hsCRP will be assayed.
Aim 3:
Objective 1: assess the effects of medium-term LLTS on vascular endothelial function -Flow-mediated vasodilatation (FMD) will be used to assess %-change in brachial artery diameter upon the release of temporary 5-min blood flow occlusion to the extremity using ultrasonography (Phillips Affinity X70). This is a standard, validated technique to assess FMD. Average time to perform this study is ~20 minutes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Device: neuromodulation deviceActive LLTS will be performed by use of a neuromodulation device with electrodes attached to the tragus of the ear. Stimulator will be applied continuously for 1 hour daily for 12 weeks. |
| Control arm | Sham comparator | Device: SHAMSham LLTS will be performed by use of a neuromodulation device with electrodes attached to the ear lobule. Stimulator will be applied continuously for 1 hour daily for 12 weeks. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Systolic heart failure with EF < or equal to 50%.
Key exclusion criteria (7 listed)
- patients in overt congestive heart failure / recent acute myocardial infarction (< 4 weeks) or Unstable angina
- Active malignancy
- unilateral or bilateral vagotomy
- pregnant patients
- End stage liver disease
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 |
|---|---|---|
| neuromodulation deviceActive LLTS will be performed by use of a neuromodulation device with electrodes attached to the tragus of the ear. Stimulator will be applied continuously for 1 hour daily for 12 weeks | Device | Experimental |
| SHAMSham LLTS will be performed by use of a neuromodulation device with electrodes attached to the ear lobule. Stimulator will be applied continuously for 1 hour daily for 12 weeks | Device | Control arm |
Primary outcome
6MWD
Time frame: Change in 6MWD after 12 weeks compared to baseline
6 minute walk distance
1 secondary outcome
QoL
Time frame: Change in QoL after 12 weeks compared to baseline
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 11 Aug 2026.
- Individual participant dataSharing planned: No
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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, MPH 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 study testing neuromodulation device in people with Systolic Heart Failure, 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?
The sponsor lists 1 inclusion and 7 exclusion criteria. 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: looking for participants now, as of the sponsor's last update on 11 Aug 2026. 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.
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,MPH (4052714742, tdasari@ouhsc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6MWD (time frame: Change in 6MWD after 12 weeks compared to baseline). 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 11 Aug 2026.