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Completed

NCT Number: NCT03327649

Neuromodulation to Treat Patients With 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.

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Key information

Conditions

Heart Failure With Normal Ejection Fraction Inflammation Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

21 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Low Level Transcutaneous Vagus Nerve Stimulation

Device

Stimulation of the auricular branch of the vagus nerve

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. Exercise Capacity

    Time frame: 3 months

    6 minute walk test

  2. Inflammatory Cytokines

    Time frame: 3 months

    Serum inflammatory cytokines (tumor necrosis factor-alpha)

  3. 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.

Sponsors and collaborators

Lead sponsor

University of Oklahoma

Other

Registry information

Official study title

Neuromodulation of Inflammation to Treat Heart Failure With Preserved Ejection Fraction

Important dates

Study start
2017
Primary completion
2021
Study completion
2021
First posted
Oct 31, 2017
Registry last updated
Jan 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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