Neuromodulation to Treat Patients With Heart Failure With Preserved Ejection Fraction

NCT ID: NCT03327649

Last Updated: 2022-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-12
• Study Completion Date: 2021-09-30

Brief Summary

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.

Conditions

Heart Failure With Normal Ejection Fraction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sham control

Patients will receive 1 hour of sham transcutaneous low level vagal stimulation daily for 3 months

Group Type: SHAM_COMPARATOR

low level transcutaneous vagus nerve stimulation

Intervention Type: DEVICE

Stimulation of the auricular branch of the vagus nerve

Active treatment

Patients will receive 1 hour of active transcutaneous low level vagal stimulation daily for 3 months

Group Type: EXPERIMENTAL

low level transcutaneous vagus nerve stimulation

Intervention Type: DEVICE

Stimulation of the auricular branch of the vagus nerve

Interventions

low level transcutaneous vagus nerve stimulation

Stimulation of the auricular branch of the vagus nerve

Intervention Type: DEVICE

Eligibility Criteria

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).

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Oklahoma

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stavros Stavrakis, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Oklahoma

Locations

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Countries

United States

References

Goggins E, Inoue H, Okusa MD. Neuroimmune Control of Inflammation in Acute Kidney Injury and Multiorgan Dysfunction. J Am Soc Nephrol. 2025 Jul 7. doi: 10.1681/ASN.0000000813. Online ahead of print.

Reference Type: DERIVED

PMID: 40622772 (View on PubMed)

Stavrakis S, Elkholey K, Morris L, Niewiadomska M, Asad ZUA, Humphrey MB. Neuromodulation of Inflammation to Treat Heart Failure With Preserved Ejection Fraction: A Pilot Randomized Clinical Trial. J Am Heart Assoc. 2022 Feb;11(3):e023582. doi: 10.1161/JAHA.121.023582. Epub 2022 Jan 13.

Reference Type: DERIVED

PMID: 35023349 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

8251

Identifier Type: -

Identifier Source: org_study_id