Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction

June 1, 2026 updated by: Benjamin Levine, University of Texas Southwestern Medical Center
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This will be a randomized, non-blinded prospective intervention testing the effects of two types of exercise training, whole body and isolated single leg, on HFpEF patients with either central or peripheral limitations to exercise training. Subjects will undergo baseline maximal exercise testing and invasive right heart catheterization to define exercise tolerance and pulmonary and cardiac pressures during exercise. Based on the results of baseline testing, subjects will be divided into either centrally limited, defined as excessive rise in pulmonary capillary wedge pressure more than 25 mmHg that decreases after administration of sub-lingual nitroglycerin resulting in improved exercise tolerance, or peripherally limited, defined as no improvement in exercise tolerance despite reduction in pulmonary capillary wedge pressure after sublingual nitroglycerin. After baseline testing, subjects will be randomized to either whole body cycle exercise supplemented with sublingual nitroglycerin to improve training responsiveness or isolated single leg exercise training for 4 months. After 4 months, subjects will repeat maximal exercise testing and invasive right heart catheterization to assess responses to 4 months of exercise training.

Study Type

Interventional

Enrollment (Actual)

93

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75231
        • The Institute for Exercise and Environmental Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Central HFpEF whole body exercise
HFpEF patients who have a central limitation as the cause of the exercise intolerance randomized to whole body cycle training.
Behavioral: Exercise training
Exercise training, either whole body or isolated single leg
Experimental: Central HFpEF isolated single leg exercise
HFpEF patients who have a central limitation as the cause of the exercise intolerance randomized to isolated single leg training.
Behavioral: Exercise training
Exercise training, either whole body or isolated single leg
Experimental: Peripheral HFpEF whole body exercise
HFpEF patients who have a peripheral limitation as the cause of the exercise intolerance randomized to whole body cycle training.
Behavioral: Exercise training
Exercise training, either whole body or isolated single leg
Experimental: Peripheral HFpEF isolated single leg exercise
HFpEF patients who have a peripheral limitation as the cause of the exercise intolerance randomized to isolated single leg training.
Behavioral: Exercise training
Exercise training, either whole body or isolated single leg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Aerobic fitness
Time Frame: 4 months
Change in peak VO2 after exercise training
4 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiopulmonary hemodynamics
Time Frame: 4 months
Change in exercise pulmonary capillary wedge pressure
4 months
Sympathetic activity
Time Frame: 4 months
Change in muscle sympathetic activity
4 months
Leg blood flow
Time Frame: 4 months
Change in leg blood flow assessed by Doppler velocities in femoral artery
4 months
Cardiac fibrosis
Time Frame: 4 months
Change in T1 mapping times by cardiac MRI
4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Collaborators

The University of Texas at Arlington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2019

Primary Completion (Actual)

August 1, 2025

Study Completion (Actual)

April 1, 2026

Study Registration Dates

First Submitted

August 22, 2019

First Submitted That Met QC Criteria

August 23, 2019

First Posted (Actual)

August 28, 2019

Study Record Updates

Last Update Posted (Actual)

June 3, 2026

Last Update Submitted That Met QC Criteria

June 1, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU-2019-0617

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Heart Failure, Diastolic

Clinical Trials on Exercise training

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Norway

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe