Chronotropic Incompetence in Patients With HFpEF

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-06-30

Study Completion Date

2017-11-15

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this study is to determine the mechanisms of chronotropic incompetence (inability to increase heart rate with exercise) in patients with heart failure and preserved ejection fraction (HFpEF). The investigators will test both central command regulation and cardiac beta-receptor sensitivity over control of heart rate.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

The Role of Chronotropic Incompetence in Heart Failure With Normal Ejection Fraction (HFNEF)

NCT02354573

Heart Failure

COMPLETED NA

Pharmacokinetics, Pharmacodynamics, and Impact of Inorganic Nitrate on Exercise in HFpEF

NCT02256345

Heart Failure Diastolic Heart Failure

COMPLETED PHASE2

Control of Sinus Node Tachycardia as an Additional Therapy in Patients With Decompensated Heart Failure

NCT02236247

Decompensated Heart Failure

UNKNOWN PHASE1/PHASE2

Safety and Efficacy Study of Once and Twice Daily Doses of MCC-135 in Subjects With Congestive Heart Failure.

NCT00050076

Congestive Heart Failure

COMPLETED PHASE2

The Re-Prosper HF Study

NCT04551222

Heart Failure

COMPLETED PHASE2/PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

About half of all elderly patients with a diagnosis of congestive heart failure have apparently normal systolic function, so called "heart failure with a preserved ejection fraction" or HFpEF. To date, no effective therapy for HFpEF has been found, in part because of failure to discern key pathophysiologic pathways.

Although HFpEF is a complex disease with multiple pathophysiologic pathways leading to the phenotype of heart failure, virtually all proposed mechanisms involve some impairment of diastolic function - the inability of the heart to fill adequately at a low enough pressure to avoid congestion which during physical activity or exercise, prevent an increase in heart rate. A number of studies have purported the inability to increase heart rate (chronotropic incompetence) is responsible for the diminished exercise capacity.

Alternatively, the investigators hypothesize that the stiff, slowly relaxing heart of patients with HFpEF causes a marked elevation in pulmonary capillary pressure during exercise which leads to premature fatigue prior to achieving maximal heart rate, thus causing apparent "chronotropic incompetence".

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Heart Failure

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

HFpEF

Patients with HFpEF will provide data from their cardiologist or primary care physician that confirm the following: a) signs and symptoms of heart failure; b) an ejection fraction \> 0.50; and c) objective evidence of diastolic dysfunction.

Intervention: Static handgrip and Autonomic Blockade (Dexmedetomidine, Glycopyrrolate, Isoproterenol)

Group Type EXPERIMENTAL

Static Handgrip

Intervention Type OTHER

Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.

Dexmedetomidine

Intervention Type DRUG

Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.

Glycopyrrolate

Intervention Type DRUG

Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.

Isoproterenol

Intervention Type DRUG

Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.

Healthy Young

Fifteen volunteers \<45 yrs will be enrolled. Subjects will be healthy with no chronic medical problems and on no cardiac medications except for statins and have BMI \<30.

Intervention: Autonomic Blockade (Dexmedetomidine, Glycopyrrolate, Isoproterenol)

Group Type ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type DRUG

Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.

Glycopyrrolate

Intervention Type DRUG

Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.

Isoproterenol

Intervention Type DRUG

Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.

Healthy Seniors

Fifteen healthy senior volunteers \> 60 years of age. Subjects will be healthy with no chronic medical problems and on no cardiac medications except for statins. All control subjects will have a Body Mass Index (BMI) \<30, with exercise histories of less than 3 days per week of aerobic exercise.

Intervention: Static handgrip and Autonomic Blockade (Dexmedetomidine, Glycopyrrolate, Isoproterenol)

Group Type ACTIVE_COMPARATOR

Static Handgrip

Intervention Type OTHER

Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.

Dexmedetomidine

Intervention Type DRUG

Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.

Glycopyrrolate

Intervention Type DRUG

Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.

Isoproterenol

Intervention Type DRUG

Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Static Handgrip

Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.

Intervention Type OTHER

Dexmedetomidine

Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.

Intervention Type DRUG

Glycopyrrolate

Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.

Intervention Type DRUG

Isoproterenol

Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Sympathetic blockade Parasympathetic blockade Beta-receptor sensitivity testing

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* ages \> 60 years
* body mass index \<30
* absence of co-morbid conditions including hypertension, diabetes, heart failure, asthma, chronic obstructive pulmonary disease, coronary artery disease as evidenced by angina or prior myocardial infarction or cerebrovascular disease as evidenced by prior transient ischemic attack or stroke

* Patients will be \> 60 years old, male or female, all races.
* signs and symptoms of heart failure
* ejection fraction \> 0.50
* objective evidence of diastolic dysfunction.
* All patients must be in sinus rhythm without a left bundle branch block at the time of study

Exclusion Criteria

* ages less than 60
* body mass index \>30
* presence of co-morbid conditions including hypertension, diabetes, heart failure, asthma, chronic obstructive pulmonary disease, coronary artery disease as evidenced by angina or prior myocardial infarction or cerebrovascular disease as evidenced by prior transient ischemic attack or stroke
* Patients with chronic orthopedic injury that might make them unable to participate in an exercise testing will also be excluded
* Subjects unable to speak English will not be recruited because of the complex experimental studies and the need for precise communication between the volunteers and the research staff to ensure safety.

HFpEF Subjects

* underlying valvular or congenital heart disease
* restrictive or infiltrative cardiomyopathy
* acute myocarditis
* New York Heart Association (NYHA) Class IV congestive heart failure, or heart failure that cannot be stabilized on medical therapy
* other condition that would limit the patient's ability to complete the protocol
* manifest ischemic heart disease
* Coumadin/warfarin therapy
* Patients with chronic orthopedic injury that might make them unable to participate in an exercise testing will also be excluded
* Subjects unable to speak English will not be recruited because of the complex experimental studies and the need for precise communication between the volunteers and the research staff to ensure safety.

Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes