Neuromodulation to Treat Patients With Heart Failure With Preserved Ejection Fraction

January 6, 2026 updated by: University of Oklahoma

Neuromodulation of Inflammation to Treat Heart Failure With Preserved Ejection Fraction

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

52

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • HFpEF, defined as signs and symptoms of heart failure, LV ejection fraction ≥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:

    • age ≥ 65,
    • diabetes,
    • hypertension and
    • obesity, defined as body mass index ≥30kg/m2

Exclusion Criteria:

  • LV ejection fraction <40%
  • significant valvular disorder (i.e., prosthetic valve or hemodynamically significant valvular diseases)
  • recent (<6 months) stroke, myocardial infarction or hospitalization for heart failure
  • severe heart failure (class III or IV)
  • end stage kidney disease
  • recurrent vasovagal syncope
  • history of vagotomy
  • pregnancy
  • sick sinus syndrome and 2nd or 3rd degree AV block (without a pacemaker).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Sham control
Patients will receive 1 hour of sham 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
Experimental: Active treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
E/e' (Early Mitral Inflow Doppler Velocity to the Early Diastolic Mitral Annulus Velocity)
Time Frame: 3 months
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.
3 months
Global Longitudinal Strain
Time Frame: 3 months
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.
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exercise Capacity
Time Frame: 3 months
6 minute walk test
3 months
Inflammatory Cytokines
Time Frame: 3 months
Serum inflammatory cytokines (tumor necrosis factor-alpha)
3 months
Minnesota Living With Heart Failure Questionnaire
Time Frame: 3 months
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.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oklahoma

Investigators

  • Principal Investigator: Stavros Stavrakis, MD, PhD, University of Oklahoma

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 12, 2017

Primary Completion (Actual)

March 30, 2021

Study Completion (Actual)

September 30, 2021

Study Registration Dates

First Submitted

October 27, 2017

First Submitted That Met QC Criteria

October 30, 2017

First Posted (Actual)

October 31, 2017

Study Record Updates

Last Update Posted (Actual)

January 23, 2026

Last Update Submitted That Met QC Criteria

January 6, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 8251

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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).

IPD Sharing Time Frame

12 months after study completion

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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