An interventional study of low level transcutaneous vagus nerve stimulation in Heart Failure With Normal Ejection Fraction, sponsored by University of Oklahoma. Completed at 1 site in United States. Open to participants aged 21 Years to 90 Years. Per ClinicalTrials.gov, last updated 2026-01-23.
Sponsored by University of Oklahoma · Not applicable, Interventional, and Treatment
Heart failure with preserved ejection fraction (HFpEF) is a leading cause of mortality in the elderly. Outcomes of patients with HFpEF are poor and so far, no treatment has been shown to decrease morbidity or mortality. Recent animal and human studies suggest that a systemic proinflammatory state, produced by comorbidities, including aging, plays a central role in the development of HFpEF, supporting the notion that attenuating the proinflammatory state is an attractive therapeutic target for HFpEF. We have previously shown that low-level transcutaneous electrical stimulation of the vagus nerve (tVNS) suppresses inflammation in patients with atrial fibrillation. The overall objective of this proposal is to examine the effects of tVNS on diastolic dysfunction, exercise capacity and inflammation in patients with HFpEF. Our specific aims include: 1. To examine the effect of intermittent (1 hour daily for 3 months) tVNS on diastolic dysfunction and exercise capacity, relative to sham stimulation, in patients with HFpEF and 2. To examine the effect of intermittent (1 hour daily for 3 months) LLTS on inflammatory cytokines relative to sham stimulation, in patients with HFpEF. The proposed proof-of-concept studies will provide the basis for the design of further human studies using LLTS among populations with HFpEF. In light of the increasing number of elderly patients with HFpEF and the poor success of the currently available treatment options, an alternative and novel approach such as tVNS has the potential to impact clinical practice and improve health outcomes among a large number of patients. It is anticipated that these investigations will contribute to the broader understanding of the role of inflammation in the pathogenesis of HFpEF and how its inhibition can be used to provide therapeutic effects. Moreover, it is anticipated that a better understanding of how modulation of inflammation affects one of the hallmarks of HFpEF, diastolic dysfunction, will lead to the development of novel pharmacological and non-pharmacological approaches to treat this disease.
3,536 studies on the registry are indexed under Inflammation; 642 are open to participants now.
This study's enrollment of 52 is close to the median of 50 across 2,577 interventional studies indexed under Inflammation.
Browse Inflammation studies →University of Oklahoma is the lead sponsor of 432 studies on the registry; 100 are open to participants now.
Of its 42 completed or terminated interventional studies of FDA-regulated products, 16 (38%) have results posted.
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HFpEF, defined as signs and symptoms of heart failure, LV ≥50%, brain natriuretic peptide ≥35pg/mL and echocardiographic evidence of diastolic dysfunction (left atrial volume index ≥34mL/m2, mitral E-wave velocity/mitral annular velocity ratio [E/e']≥13 and e'\<9cm/s) plus 2 of the following 4 comorbidities:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients will receive 1 hour of sham transcutaneous low level vagal stimulation daily for 3 months
Device: low level transcutaneous vagus nerve stimulation
Patients will receive 1 hour of active transcutaneous low level vagal stimulation daily for 3 months
Device: low level transcutaneous vagus nerve stimulation
Stimulation of the auricular branch of the vagus nerve
E/e' (Early Mitral Inflow Doppler Velocity to the Early Diastolic Mitral Annulus Velocity)
E/e' was measured by echocardiography. E/e' correlates very well with left ventricular end diastolic pressure. Higher numbers indicate elevated left ventricular end diastolic pressure.
Time frame: 3 months
Global Longitudinal Strain
Global longitudinal strain was measured by echocardiography. It is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values. Reduced global longitudinal strain has been associated with adverse clinical outcomes irrespective of left ventricular ejection fraction.
Time frame: 3 months
Exercise Capacity
6 minute walk test
Time frame: 3 months
Inflammatory Cytokines
Serum inflammatory cytokines (tumor necrosis factor-alpha)
Time frame: 3 months
Minnesota Living With Heart Failure Questionnaire
The Minnesota Living with Heart Failure Questionnaire is a well validated measure of quality of life in patients with heart failure. It can have a score 0 to 105, with higher scores reflecting worse quality of life.
Time frame: 3 months
| Milestone | Sham Control | Active Treatment |
|---|---|---|
| Started | 26 | 26 |
| Completed | 24 | 24 |
| Not completed | 2 | 2 |
E/e' was measured by echocardiography. E/e' correlates very well with left ventricular end diastolic pressure. Higher numbers indicate elevated left ventricular end diastolic pressure.
| ratio | Sham Control | Active Treatment |
|---|---|---|
| E/e' (Early Mitral Inflow Doppler Velocity to the Early Diastolic Mitral Annulus Velocity) | 10.4 ± 1.5 | 9.9 ± 1.5 |
Global longitudinal strain was measured by echocardiography. It is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values. Reduced global longitudinal strain has been associated with adverse clinical outcomes irrespective of left ventricular ejection fraction.
| percentage of myocardial shortening | Sham Control | Active Treatment |
|---|---|---|
| Global Longitudinal Strain | -16.1 ± 2.5 | -18.6 ± 2.5 |
6 minute walk test
| meters | Sham Control | Active Treatment |
|---|---|---|
| Exercise Capacity | 326.9 ± 140.4 | 352.7 ± 158.8 |
Serum inflammatory cytokines (tumor necrosis factor-alpha)
| pg/mL | Sham Control | Active Treatment |
|---|---|---|
| Inflammatory Cytokines | 11.3 ± 2.5 | 8.7 ± 2.2 |
The Minnesota Living with Heart Failure Questionnaire is a well validated measure of quality of life in patients with heart failure. It can have a score 0 to 105, with higher scores reflecting worse quality of life.
| units on a scale | Sham Control | Active Treatment |
|---|---|---|
| Minnesota Living With Heart Failure Questionnaire | 36.6 ± 14.8 | 23.8 ± 14.8 |
Collected over 3 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Sham Control | 0/24 (0%) | 0/24 (0%) | 3/24 (12.5%) |
| Active Treatment | 0/24 (0%) | 0/24 (0%) | 4/24 (16.7%) |
| Event | Sham Control | Active Treatment |
|---|---|---|
| hospitalizationCardiac disorders | 3/24 | 4/24 |
| Age, Categorical(Participants) | Sham Control | Active Treatment | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 8 | 7 | 15 |
| >=65 years | 16 | 17 | 33 |
| Age, Continuous(years) | Sham Control | Active Treatment | Total |
|---|---|---|---|
| Mean | 70.3 ± 9.1 | 69.8 ± 8.8 | 70.1 ± 8.9 |
| Sex: Female, Male(Participants) | Sham Control | Active Treatment | Total |
|---|---|---|---|
| Female | 16 | 16 | 32 |
| Male | 8 | 8 | 16 |
| Race (NIH/OMB)(Participants) | Sham Control | Active Treatment | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 1 | 1 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 4 | 4 | 8 |
| White | 20 | 19 | 39 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Sham Control | Active Treatment | Total |
|---|---|---|---|
| United States | 24 | 24 | 48 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — A biologic repository will be maintained and consideration of its use for future research (linked only to de-identified data) will be integrated into the initial informed consent process for this study. Data needed for independent verification of research results will be made publicly available within 12 months of the end of the funding period (and any no-cost extension).
Time frame: 12 months after study completion
Ran from Dec 2017 to primary completion in Mar 2021, 39 months.
Results were first posted in Sep 2022, 1 year 5 months after primary completion.
Of 877 non-industry interventional studies with no phase under Inflammation, half reached primary completion within 18 months of starting (the median), counting those still running; a quarter within 8 and three quarters within 36. This study's 39 months is above that.
Counting every sponsor, half of 924 studies reached it within 18 months; a quarter within 8 and three quarters within 36.
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This study is completed, as verified in Jan 2026. You cannot join it, but the record below documents what was studied.
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