Neuromodulation of Inflammation and Endothelial Function

NCT05230732 | Recruiting DMC FDA Device

• 2 other identifiers: 141015R21AG075639-02
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 1

Brief Summary

Heart failure with reduced ejection fraction (HFrEF) is a major cause of mortality in United States. Aging is a major risk factor for adverse outcomes associated with HFrEF, with majority of the patient's over the age of 50, continuing to experience symptoms, reduced exercise capacity and poor quality of life. We have previously demonstrated that low level transcutaneous electrical stimulation of the vagus nerve at the tragus (LLTS) suppresses inflammation in patients with atrial fibrillation and diastolic dysfunction and improved endothelial dysfunction in patients with chronic heart failure. The overall objective of this proposal is to examine the effects of LLTS on heart failure symptoms, exercise capacity and quality of life in patients with HFrEF and simultaneously determine the impact of LLTS on the suppression of inflammation and improvement in endothelial function. Our specific aims include: 1. To examine the medium term effect of intermittent (1 hour daily for 3 months) LLTS on exercise capacity and quality of life, related to sham stimulation, in patients with HFrEF, 2. To determine the effects of medium-term LLTS on sympathovagal/autonomic balance (assessed by heart rate variability) and systemic inflammation in patients with HFrEF and 3. To determine the effects of medium-term LLTS on endothelial function in patients with HFrEF. The proposed proof-of-concept human studies will provide the basis for the design of further human studies using LLTS among larger populations with HFrEF. In light of the increasing number of elderly patients who continue to experience HFrEF symptoms, recognized is a key point of interest in this funding mechanism, and the suboptimal success of the currently available treatment options to ameliorate the problems mentioned above, an alternative novel approach such as LLTS has the potential to impact clinical practice and improve health outcomes among the large number of patients. It is anticipated that these investigations will contribute to a broader understanding of the role of autonomic imbalance, inflammation and endothelial dysfunction in the pathogenesis of HFrEF and how its inhibition can be used to provide therapeutic effects. Moreover, it is anticipated that a better understanding of how modulation of autonomic tone, inflammation and endothelial function affects one of the hallmarks of HFrEF will lead to the development of normal nonpharmacological and pharmacological approaches to treat this disease.

Conditions

Systolic Heart Failure

Outcome Measures

Primary Outcomes (1)

• 6MWD

  6 minute walk distance

  Change in 6MWD after 12 weeks compared to baseline

Secondary Outcomes (1)

• QoL

  Change in QoL after 12 weeks compared to baseline

Other Outcomes (3)

• FMD

  Change in FMD after 12 weeks compared to baseline

• HRV

  Change in HRV after 12 weeks compared to baseline

• Inflammation

  Change in inflammatory markers after 12 weeks compared to baseline

Study Arms (2)

Experimental

EXPERIMENTAL

Active LLTS will be performed by use of a neuromodulation device with electrodes attached to the tragus of the ear. Stimulator will be applied continuously for 1 hour daily for 12 weeks.

Device: neuromodulation device

Control arm

SHAM COMPARATOR

Sham LLTS will be performed by use of a neuromodulation device with electrodes attached to the ear lobule. Stimulator will be applied continuously for 1 hour daily for 12 weeks.

Device: SHAM

Interventions

neuromodulation device DEVICE

Active LLTS will be performed by use of a neuromodulation device with electrodes attached to the tragus of the ear. Stimulator will be applied continuously for 1 hour daily for 12 weeks

Experimental

SHAM DEVICE

Sham LLTS will be performed by use of a neuromodulation device with electrodes attached to the ear lobule. Stimulator will be applied continuously for 1 hour daily for 12 weeks

Control arm

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Systolic heart failure with EF \< or equal to 50%.

You may not qualify if:

• patients in overt congestive heart failure / recent acute myocardial infarction (\< 4 weeks) or Unstable angina
• Active malignancy
• unilateral or bilateral vagotomy
• pregnant patients
• End stage liver disease
• history of recurrent vasovagal syncope, Sick sinus syndrome with no pacemaker, 2nd or 3rd degree AV block.
• Significant hypotension (Blood pressure \< 90 mm Hg) secondary to autonomic dysfunction

Sponsors & Collaborators

• University of Oklahoma: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73117, United States

RECRUITING

MeSH Terms

Conditions

Heart Failure, Systolic

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases

Study Officials

• Tarun Dasari, MD, MPH

  University of Oklahoma

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tarun Dasari, MD,MPH

CONTACT

4052714742; tdasari@ouhsc.edu

Cheryl Adams, RN

CONTACT

4052714742; cheryl-adams@ouhsc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: February 9, 2022
• Study Start: September 1, 2022
• Primary Completion: February 27, 2026
• Study Completion: February 27, 2026
• Last Updated: April 15, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)