Acute Decompensated Heart FailureTREAT-HFNCT02898181
Low Level Tragus Stimulation in Acute Decompensated Heart Failure
A study testing Neuromodulation in people with Acute Decompensated Heart Failure, run by University of Oklahoma at 1 site in United States.
Trial summary
Acute Decompensated Heart Failure (ADHF) is a major cause of morbidity and mortality. It is associated with increased systemic inflammation. Previous studies have demonstrated increased levels of cytokines such as C-reactive protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10) and Tumor… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Decompensated Heart Failure
- What is being tested?
- Neuromodulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Sep 2016to Dec 2026
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients admitted with ADHF
Who cannot join
- Refusal to consent
- Complex congenital heart disease (Tetralogy of Fallot patients, single ventricle physiology)
- Recurrent vaso-vagal syncopal episodes
- Unilateral or bilateral vagotomy
- Sick sinus syndrome
- 2nd or 3rd degree AV block
Show all 11Show fewer
- bifascicular block or prolonged 1st degree AV block (PR>300ms)
- Pregnant patients
- Prisoners
- End stage renal disease on dialysis
- Acute Myocardial infarction
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
OUHSC
Oklahoma City, Oklahoma, 73104
Tarun Dasari, 405-271-4742 ext. 44761, tarun-dasari@ou.edu
Diana Dalton, 4052714742 ext. 44761, diana-dalton@ou.edu
About this study
Official title: Low Level Transcutaneous Tragus Stimulation to Reduce Inflammation, Dyspnea and Improve Heart Rate Variability in Acute Decompensated Heart Failure
Acute Decompensated Heart Failure (ADHF) is a major cause of morbidity and mortality. It is associated with increased systemic inflammation. Previous studies have demonstrated increased levels of cytokines such as C-reactive protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10) and Tumor Necrosis Factor alpha (TNFα) in patients with heart failure (HF). Increased activity of sympathetic nervous system in ADHF is linked to inflammation. Previous anti-inflammatory drug therapies in HF have demonstrated no significant impact on cardiovascular outcomes. Low-level vagus nerve stimulation (LLVNS) is a non-invasive way to modulate autonomic tone and thereby inflammation. Vagal nerve stimulation is thought to increase the parasympathetic activity and suppress the sympathetic activity. Clinical studies of vagal stimulation in chronic HF have been negative. Recent experimental and clinical data suggest that low level tragus nerve stimulation (LLTNS) may produce the same desired neuromodulator effect compared to LLVNS. It is however unknown if LLTNS in ADHF will directly lead to a reduction in the levels of pro-inflammatory cytokines (CRP, IL-1, IL-6 and TNF-α) and an increase in the level of anti-inflammatory marker IL-10. heart rate variability may also be abnormal in ADHF. The objective of this proposal is to determine the impact of LLTS on inflammatory cytokines, heart failure biomarkers(Pro BNP) and HRV in patients with ADHF.In addition we will study the impact on dyspnea resolution and change in renal function during hospitalization.
Patients will be randomized to either active or sham stimulation (2 hours daily). Serum collected will (post-admission and discharge day) will be used for cytokine measurement. We will also measure daily ECG to assess HRV and patient assessed dyspnea scale.This investigation will likely establish the first evidence of the effects of LLTS on the suppression of inflammation and improvement in dyspnea, natriuretic peptides, renal function and HRV in patients presenting with ADHF.
Read the detailed description
Acute Decompensated Heart Failure (ADHF) is a major cause of morbidity and mortality. It is associated with increased systemic inflammation and poor outcomes.
Previous studies have demonstrated increased inflammation in patients with heart failure (HF). Increased activity of sympathetic nervous system in ADHF is linked to inflammation. Previous anti-inflammatory drug therapies in HF have demonstrated no significant impact on cardiovascular outcomes.
Low-level vagus nerve stimulation via stimulation of teh Tragus (LLTS) is a non-invasive way to modulate autonomic tone and thereby inflammation. Vagal nerve stimulation is thought to increase the parasympathetic activity and suppress the sympathetic activity. Recent experimental and clinical data suggest that low level tragus nerve stimulation (LLTS) may produce the same desired neuromodulator effect compared to LLVNS.
It is however unknown if LLTS in ADHF will directly lead to sympathetic tone reduction and increase in parasympathetic tone, or neuromodulation and lead to reduction in the levels of pro-inflammatory cytokines (CRP, IL-1, IL-6 and TNF-α) and an increase in the level of anti-inflammatory marker IL-10.
Autonomic tone could be assessed using heart rate variability. The objective of this proposal is to determine the impact of LLTS on inflammatory cytokines and HRV in patients with ADHF.
Patients will be randomized to either active or sham stimulation (2 hours daily).
Serum collected will (post admission and discharge day) will be used for cytokine and biomarker measurement. We will also measure 10-15 minute ECG to assess HRV. Dyspnea will be determined using patient assessment tool(visual analog scale).This investigation will likely establish the first evidence of effects of LLTS on suppression of inflammation and improvement in dyspnea scale, renal function and HRV in patients presenting with ADHF.
- Conditions
- Acute Decompensated Heart Failure
- Being tested
- Neuromodulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeuromodulationDevice
Active LLTS will be performed by use of a transcutaneous electrical nerve stimulation Parasym neuromodulation system with electrodes attached to the ear. Neuromodulation will be applied continuously for 2 hours daily.
| Study group | Role | What they receive |
|---|---|---|
| Tragus Stimulation | Experimental | In this group patients will receive neuromodulation for 2 hours daily Receives: Device: Neuromodulation |
| Control group | No intervention | Sham neuromodulation will be done |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Interleukin (IL) levels
Interleukin level
Measured: From admission to discharge- over average 3-6 days
Change in TNF-alpha levels
TNF level
Measured: From admission to discharge- over average 3-6 days
Change in CRP levels
CRP level
Measured: From admission to discharge- over average 3-6 days
Change in Pro BNP and renal function(creatinine) levels
Pro BNP level
Measured: From admission to discharge- over average 3-6 days
Secondary outcomes (1)
Change in HRV
Heart rate variability measures such time and frequency domains
Measured: From admission to discharge- over average 3-6 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2016 (estimated)
- Study start16 Sep 2016
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Decompensated Heart FailureStudies of the same condition, open and under way.
- 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Collaborators
- Oklahoma Heart Hospital
- Responsible party
- Sponsor
- Investigators
- Tarun Dasari, MD,MPH, Principal investigator, OUHSC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02898181
- Sponsor's protocol ID
- 6778
- Acronym
- TREAT-HF
- Status last verified
- Oct 2026
- First submitted
- 1 Sep 2016
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- Individual data sharing
- No
Publications
Dasari TW, Chakraborty P, Mukli P, Akhtar K, Yabluchanskiy A, Cunningham MW, Csiszar A, Po SS. Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure. Clin Auton Res. 2023 Dec;33(6):767-775. doi: 10.1007/s10286-023-00997-z. Epub 2023 Nov 9.
PubMed 37943335Dasari T, Chakraborty P, Mukli P, Akhtar K, Yabluchanskiy A, Cunningham MW, Csiszar A, Po SS. Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure. Res Sq [Preprint]. 2023 Sep 11:rs.3.rs-3323086. doi: 10.21203/rs.3.rs-3323086/v1.
PubMed 37790298
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Level Transcutaneous Tragus Stimulation to Reduce Inflammation, Dyspnea and Improve Heart Rate Variability in Acute Decompensated Heart Failure
- ClinicalTrials.gov ID
- NCT02898181
- Acronym / sponsor ID
- TREAT-HF / 6778
- Conditions
- Acute Decompensated Heart Failure
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Collaborators
- Oklahoma Heart Hospital
- Study start
- 16 Sep 2016 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 13 Sep 2016 (estimated)
- 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.
Acute Decompensated Heart Failure (ADHF) is a major cause of morbidity and mortality. It is associated with increased systemic inflammation. Previous studies have demonstrated increased levels of cytokines such as C-reactive protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10) and Tumor Necrosis Factor alpha (TNFα) in patients with heart failure (HF). Increased activity of sympathetic nervous system in ADHF is linked to inflammation. Previous anti-inflammatory drug therapies in HF have demonstrated no significant impact on cardiovascular outcomes. Low-level vagus nerve stimulation (LLVNS) is a non-invasive way to modulate autonomic tone and thereby inflammation. Vagal nerve stimulation is thought to increase the parasympathetic activity and suppress the sympathetic activity. Clinical studies of vagal stimulation in chronic HF have been negative. Recent experimental and clinical data suggest that low level tragus nerve stimulation (LLTNS) may produce the same desired neuromodulator effect compared to LLVNS. It is however unknown if LLTNS in ADHF will directly lead to a reduction in the levels of pro-inflammatory cytokines (CRP, IL-1, IL-6 and TNF-α) and an increase in the level of anti-inflammatory marker IL-10. heart rate variability may also be abnormal in ADHF. The objective of this proposal is to determine the impact of LLTS on inflammatory cytokines, heart failure biomarkers(Pro BNP) and HRV in patients with ADHF.In addition we will study the impact on dyspnea resolution and change in renal function during hospitalization.
Patients will be randomized to either active or sham stimulation (2 hours daily). Serum collected will (post-admission and discharge day) will be used for cytokine measurement. We will also measure daily ECG to assess HRV and patient assessed dyspnea scale.This investigation will likely establish the first evidence of the effects of LLTS on the suppression of inflammation and improvement in dyspnea, natriuretic peptides, renal function and HRV in patients presenting with ADHF.
Detailed description
Acute Decompensated Heart Failure (ADHF) is a major cause of morbidity and mortality. It is associated with increased systemic inflammation and poor outcomes.
Previous studies have demonstrated increased inflammation in patients with heart failure (HF). Increased activity of sympathetic nervous system in ADHF is linked to inflammation. Previous anti-inflammatory drug therapies in HF have demonstrated no significant impact on cardiovascular outcomes.
Low-level vagus nerve stimulation via stimulation of teh Tragus (LLTS) is a non-invasive way to modulate autonomic tone and thereby inflammation. Vagal nerve stimulation is thought to increase the parasympathetic activity and suppress the sympathetic activity. Recent experimental and clinical data suggest that low level tragus nerve stimulation (LLTS) may produce the same desired neuromodulator effect compared to LLVNS.
It is however unknown if LLTS in ADHF will directly lead to sympathetic tone reduction and increase in parasympathetic tone, or neuromodulation and lead to reduction in the levels of pro-inflammatory cytokines (CRP, IL-1, IL-6 and TNF-α) and an increase in the level of anti-inflammatory marker IL-10.
Autonomic tone could be assessed using heart rate variability. The objective of this proposal is to determine the impact of LLTS on inflammatory cytokines and HRV in patients with ADHF.
Patients will be randomized to either active or sham stimulation (2 hours daily).
Serum collected will (post admission and discharge day) will be used for cytokine and biomarker measurement. We will also measure 10-15 minute ECG to assess HRV. Dyspnea will be determined using patient assessment tool(visual analog scale).This investigation will likely establish the first evidence of effects of LLTS on suppression of inflammation and improvement in dyspnea scale, renal function and HRV in patients presenting with ADHF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tragus Stimulation | Experimental | Device: NeuromodulationIn this group patients will receive neuromodulation for 2 hours daily |
| Control group | No intervention | –Sham neuromodulation will be done |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients admitted with ADHF
Key exclusion criteria (11 listed)
- Refusal to consent
- Complex congenital heart disease (Tetralogy of Fallot patients, single ventricle physiology)
- Recurrent vaso-vagal syncopal episodes
- Unilateral or bilateral vagotomy
- Sick sinus syndrome
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 |
|---|---|---|
| NeuromodulationActive LLTS will be performed by use of a transcutaneous electrical nerve stimulation Parasym neuromodulation system with electrodes attached to the ear. Neuromodulation will be applied continuously for 2 hours daily. | Device | Tragus Stimulation |
Primary outcome
Change in Interleukin (IL) levels
Time frame: From admission to discharge- over average 3-6 days
Interleukin level
Change in TNF-alpha levels
Time frame: From admission to discharge- over average 3-6 days
TNF level
Change in CRP levels
Time frame: From admission to discharge- over average 3-6 days
CRP level
Change in Pro BNP and renal function(creatinine) levels
Time frame: From admission to discharge- over average 3-6 days
Pro BNP level
1 secondary outcome
Change in HRV
Time frame: From admission to discharge- over average 3-6 days
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 13 Oct 2026.
- Derived from this study: PubMed 37943335Dasari TW, Chakraborty P, Mukli P, Akhtar K, Yabluchanskiy A, Cunningham MW, Csiszar A, Po SS. Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure. Clin Auton Res. 2023 Dec;33(6):767-775. doi: 10.1007/s10286-023-00997-z. Epub 2023 Nov 9.
- Derived from this study: PubMed 37790298Dasari T, Chakraborty P, Mukli P, Akhtar K, Yabluchanskiy A, Cunningham MW, Csiszar A, Po SS. Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure. Res Sq [Preprint]. 2023 Sep 11:rs.3.rs-3323086. doi: 10.21203/rs.3.rs-3323086/v1.
- 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
OUHSC
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 in people with Acute Decompensated 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 11 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 13 Oct 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. 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 ext. 44761, tarun-dasari@ou.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Interleukin (IL) levels (time frame: From admission to discharge- over average 3-6 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02898181, which also lists 2 linked publications.
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 13 Oct 2026.