Paced Heart Rate Acceleration for Cardiac Conditioning

NCT06332391 | Recruiting DMC

• 2 other identifiers: 202308349R01HL168752
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

A clinical trial of exercise-similar heart rate acceleration delivered via cardiac pacing vs. sham intervention in subjects at rest will be performed. The study population comprises subjects with guideline-directed medically managed left ventricular dysfunction due to ischemic or non-ischemic cardiomyopathy and an existing implantable cardioverter defibrillator or biventricular implantable cardioverter defibrillator. The purpose of the study is to understand how the heart rate pattern of exercise contributes to the considerable cardiac conditioning effects of exercise and estimate whether the pacing approach may have translational clinical applicability. Fifty-two subjects will be randomized, single-blinded, to either the pacing intervention or a sham intervention which they will receive once daily, 3 days/week for 6 weeks. Baseline symptoms and clinical test results will be compared to the same measures at 2 weeks, 4 weeks and 6 weeks of intervention/sham and at 3 months and one-year post-intervention. The primary endpoint will be the change in left ventricular ejection fraction from baseline in intervention vs. sham groups (mixed effects linear regression with time and treatment arm as fixed effects and pre-specified covariates of sex and cardiomyopathy type as random effects). Secondary endpoints will include changes in quality of life, 6-minute walk distance, cardiopulmonary exercise test (CPET) measures, daily activity and major adverse cardiac events (MACE) at 3 and 12 months between pacing and sham groups. A "dose-response" analysis of outcomes at 2, 4, and 6 weeks of the intervention vs. sham compared with baseline will be performed.

Conditions

Heart Failure, Systolic

Keywords

heart failure; exercise; heart rate; implantable defibrillator; cardiac conditioning; exercise tolerance; pacing; cardiac output; quality of life; walking distance

Outcome Measures

Primary Outcomes (1)

• Change in left ventricular ejection fraction by echocardiogram

  The change in left ventricular ejection fraction from baseline as determined by echocardiography

  at baseline versus 2 weeks, 4 weeks, 6 weeks from start of intervention/sham and at 3 months and 12 months after completion of intervention vs. sham.

Secondary Outcomes (19)

• Quality of Life score on the Minnesota Living with Heart Failure questionnaire

  at baseline versus 2 weeks, 4 weeks, 6 weeks from start of intervention/sham and at 3 months and 12 months after completion of intervention vs. sham.

• Quality of Life score on the Kansas City Cardiomyopathy Questionnaire

  at baseline versus 2 weeks, 4 weeks, 6 weeks from start of intervention/sham and at 3 months and 12 months after completion of intervention vs. sham.

• 6-minute walk distance

  at baseline versus 2 weeks, 4 weeks, 6 weeks from start of intervention/sham and at 3 months and 12 months after completion of intervention vs. sham.

• Cardiopulmonary exercise test maximum oxygen consumption

  at baseline versus 2 weeks, 4 weeks, 6 weeks from start of intervention/sham and at 3 months and 12 months after completion of intervention vs. sham.

• Cardiopulmonary exercise test metabolic equivalents achieved

  at baseline versus 2 weeks, 4 weeks, 6 weeks from start of intervention/sham and at 3 months and 12 months after completion of intervention vs. sham.

Study Arms (2)

Exercise-similar cardiac pacing

EXPERIMENTAL

Atrial pacing to replicate exercise heart rate envelope once daily, 3 days per week, over 6 weeks while symptoms and vital signs are monitored and outcome measures assessed.

Device: Exercise-similar cardiac pacing

Sham cardiac pacing

SHAM COMPARATOR

Sham pacing to replicate exercise heart rate envelope once daily, 3 days per week, over 6 weeks while symptoms and vital signs are monitored and outcome measures assessed.

Device: Sham cardiac pacing

Interventions

Exercise-similar cardiac pacing DEVICE

Cardiac pacing using subjects already-implanted cardioverter defibrillator to reproduced exercise heart rate envelope.

Exercise-similar cardiac pacing

Sham cardiac pacing DEVICE

Simulated (rates selected using programmer but not initiated) cardiac pacing using subjects already-implanted cardioverter defibrillator to reproduced exercise heart rate envelope.

Sham cardiac pacing

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female sex
• Age 18 years or greater
• Available transportation for study visits
• Left ventricular ejection fraction \< or = 40% despite at least 3 months guideline-directed medial therapy
• NYHA class II-III heart failure symptoms
• Atrial-lead inclusive implantable cardioverter defibrillator or biventricular defibrillator in place \> 3 months
• Intrinsic or biventricular paced QRS duration of \<= 120 milliseconds

You may not qualify if:

• Age \< 18 years
• Inability to ambulate safely
• Congenital or primary valve disease
• Ongoing (not suppressed) atrial arrhythmias
• Left ventricular thrombus
• Severe peripheral arterial disease that limits mobility
• Hospital admission for life-threatening condition (e.g. heart failure, stroke) in the past 3 months
• Major surgery in the past 3 months or anticipated during the period of study
• Ventricular pacing indication in the absence of biventricular pacing
• Life expectancy \< 1 year
• Hemodialysis
• Hematocrit \< 30%
• Severe chronic lung disease that limits activity or requires oxygen
• Pregnancy
• Implantable cardioverter defibrillator battery longevity \< 1 year

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Denice Hodgson-Zingman, MD: lead
• The Cleveland Clinic: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

MeSH Terms

Conditions

Heart Failure, Systolic; Heart Failure; Motor Activity

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Behavior

Study Officials

• Denice Hodgson-Zingman, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Denice Hodgson-Zingman, MD

CONTACT

+1 319 384 2915; denice-zingman@uiowa.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Subjects and outcomes assessors are blinded to study group (intervention vs. sham) but investigator is not. During intervention vs. sham, subjects do not have access to vital sign data and sham procedures follow intervention procedures exactly with the exception that no change in pacing rate is delivered. A blinding questionnaire is given to subjects to assess adequacy of blinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Prospective, single blinded, randomized, controlled trial. Randomization to intervention versus sham groups in a 1:1 ratio.

Study Record Dates

• First Submitted: November 27, 2023
• First Posted: March 27, 2024
• Study Start: June 26, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

US (1)