Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction

NCT04068844 | Active Not Recruiting DMC

• 1 other identifier: STU-2019-0617
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

Brief Summary

The global objective of this study is to determine the mechanisms of exercise intolerance and dyspnea on exertion (DOE) in patients with HFpEF and based on this pathophysiology, test whether specific exercise training programs (whole body vs single leg) will result in improved exercise tolerance.

Conditions

Heart Failure, Diastolic

Keywords

Exercise; Hemodynamics,; Heart failure

Outcome Measures

Primary Outcomes (1)

• Aerobic fitness

  Change in peak VO2 after exercise training

  4 months

Secondary Outcomes (4)

• Cardiopulmonary hemodynamics

  4 months

• Sympathetic activity

  4 months

• Leg blood flow

  4 months

• Cardiac fibrosis

  4 months

Study Arms (4)

Central HFpEF whole body exercise

EXPERIMENTAL

HFpEF patients who have a central limitation as the cause of the exercise intolerance randomized to whole body cycle training.

Behavioral: Exercise training

Central HFpEF isolated single leg exercise

EXPERIMENTAL

HFpEF patients who have a central limitation as the cause of the exercise intolerance randomized to isolated single leg training.

Behavioral: Exercise training

Peripheral HFpEF whole body exercise

EXPERIMENTAL

HFpEF patients who have a peripheral limitation as the cause of the exercise intolerance randomized to whole body cycle training.

Behavioral: Exercise training

Peripheral HFpEF isolated single leg exercise

EXPERIMENTAL

HFpEF patients who have a peripheral limitation as the cause of the exercise intolerance randomized to isolated single leg training.

Behavioral: Exercise training

Interventions

Exercise training BEHAVIORAL

Exercise training, either whole body or isolated single leg

Central HFpEF isolated single leg exercise; Central HFpEF whole body exercise; Peripheral HFpEF isolated single leg exercise; Peripheral HFpEF whole body exercise

Eligibility Criteria

• Age: 60 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• signs and symptoms of heart failure
• an ejection fraction \> 0.50
• objective evidence of diastolic dysfunction

You may not qualify if:

• age \< 60 years
• BMI \> 50 kg/m2
• PDE5 inhibitor use
• Severe valvular disease
• Severe COPD
• CKD 4 or higher
• Contra-indication to MRI.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• The University of Texas at Arlington: collaborator

Study Sites (1)

The Institute for Exercise and Environmental Medicine

Dallas, Texas, 75231, United States

Location

Related Publications (5)

• Babb TG, Balmain BN, Tomlinson AR, Hynan LS, Levine BD, MacNamara JP, Sarma S. Ventilatory limitation to exercise in patients with HFpEF and obesity: No room to breathe. Respir Physiol Neurobiol. 2026 Jan 27;341:104546. doi: 10.1016/j.resp.2026.104546. Online ahead of print.

  PMID: 41615840 DERIVED

• Babb TG, Balmain BN, Tomlinson AR, Hynan LS, Levine BD, MacNamara JP, Sarma S. Ventilatory Limitation to Exercise in Patients with HFpEF and Obesity: No room to breatheVentilatory Limited Exercise in HFpEF. Respir Physiol Neurobiol. 2026 Jan 27:104546. doi: 10.1016/j.resp.2026.104546. Online ahead of print.

  PMID: 41610904 DERIVED

• Leahy MG, Wakeham DJ, MacNamara JP, Brazile T, Abulimiti A, Hearon CM Jr, Samels M, Tomlinson AR, Balmain BN, Babb TG, Levine BD, Sarma S. Heart-Lung Interactions in HFpEF: Dynamic Hyperinflation and Exercise PCWP. JACC Heart Fail. 2025 Aug;13(8):102523. doi: 10.1016/j.jchf.2025.102523. Epub 2025 Jun 26.

  PMID: 40578265 DERIVED

• Skow RJ, Sarma S, MacNamara JP, Bartlett MF, Wakeham DJ, Martin ZT, Samels M, Nandadeva D, Brazile TL, Ren J, Fu Q, Babb TG, Balmain BN, Nelson MD, Hynan LS, Levine BD, Fadel PJ, Haykowsky MJ, Hearon CM Jr. Identifying the Mechanisms of a Peripherally Limited Exercise Phenotype in Patients With Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2024 Aug;17(8):e011693. doi: 10.1161/CIRCHEARTFAILURE.123.011693. Epub 2024 Jul 25.

  PMID: 39051098 DERIVED

• Sarma S, MacNamara JP, Balmain BN, Hearon CM Jr, Wakeham DJ, Tomlinson AR, Hynan LS, Babb TG, Levine BD. Challenging the Hemodynamic Hypothesis in Heart Failure With Preserved Ejection Fraction: Is Exercise Capacity Limited by Elevated Pulmonary Capillary Wedge Pressure? Circulation. 2023 Jan 31;147(5):378-387. doi: 10.1161/CIRCULATIONAHA.122.061828. Epub 2022 Dec 16.

  PMID: 36524474 DERIVED

MeSH Terms

Conditions

Heart Failure, Diastolic; Motor Activity; Heart Failure

Interventions

Exercise

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: HFpEF patients with either central or peripheral limitations to exercise will be randomly assigned to either whole body or isolated single leg exercise.

Study Record Dates

• First Submitted: August 22, 2019
• First Posted: August 28, 2019
• Study Start: August 1, 2019
• Primary Completion: August 1, 2025
• Study Completion: December 31, 2025
• Last Updated: January 1, 2025

Record last verified: 2024-12

Locations

US (1)