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Heart Failure, DiastolicNCT04068844

Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction

A study testing Exercise training in people with Heart Failure, Diastolic, run by University of Texas Southwestern Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 60 to 90 years
Conditions the study is for
Heart Failure, Diastolic
What is being tested?
Exercise training
Could I receive a placebo?
No, everyone receives an active treatment
How many people
93 participants
Where
1 siteUnited States
Study dates
1 Aug 2019to 1 Apr 2026
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Institute for Exercise and Environmental Medicine

    Dallas, Texas, 75231

Other trials in United States

About this study

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.

Read the 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.

Being tested
Exercise training
Keywords
Exercise, Hemodynamics,, Heart failure
Medical subject headings
Heart Failure, Diastolic, Motor Activity, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Exercise trainingBehavioural

    Exercise training, either whole body or isolated single leg

Study groups in NCT04068844
Study groupRoleWhat they receive
Central HFpEF whole body exerciseExperimentalHFpEF patients who have a central limitation as the cause of the exercise intolerance randomized to whole body cycle training.
Receives: Behavioral: Exercise training
Central HFpEF isolated single leg exerciseExperimentalHFpEF patients who have a central limitation as the cause of the exercise intolerance randomized to isolated single leg training.
Receives: Behavioral: Exercise training
Peripheral HFpEF whole body exerciseExperimentalHFpEF patients who have a peripheral limitation as the cause of the exercise intolerance randomized to whole body cycle training.
Receives: Behavioral: Exercise training
Peripheral HFpEF isolated single leg exerciseExperimentalHFpEF patients who have a peripheral limitation as the cause of the exercise intolerance randomized to isolated single leg training.
Receives: Behavioral: Exercise training

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Aerobic fitness

    Change in peak VO2 after exercise training

    Measured: 4 months

Secondary outcomes (4)

  1. Cardiopulmonary hemodynamics

    Change in exercise pulmonary capillary wedge pressure

    Measured: 4 months

  2. Sympathetic activity

    Change in muscle sympathetic activity

    Measured: 4 months

  3. Leg blood flow

    Change in leg blood flow assessed by Doppler velocities in femoral artery

    Measured: 4 months

  4. Cardiac fibrosis

    Change in T1 mapping times by cardiac MRI

    Measured: 4 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2019
  2. Study start1 Aug 2019
  3. Primary completion1 Aug 2025
  4. Study completion1 Apr 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Model description
HFpEF patients with either central or peripheral limitations to exercise will be randomly assigned to either whole body or isolated single leg exercise.
Masking
None (open label)
Enrolment
93 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04068844
Sponsor's protocol ID
STU-2019-0617
Status last verified
Jun 2026
First submitted
22 Aug 2019
Last updated
3 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Hearon CM Jr, Skow RJ, Wakeham DJ, Kissell C, Brazile TL, Nelson MD, Bartlett MF, Ren J, Samels M, MacNamara JP, Taherzadeh Z, Lutz K, Levine BD, Fadel PJ, Haykowsky MJ, Sarma S. Sex differences in the peripheral determinants of oxygen transport and utilization in patients with heart failure with preserved ejection fraction. Am J Physiol Heart Circ Physiol. 2026 Jul 1;331(1):H11-H22. doi: 10.1152/ajpheart.00254.2026. Epub 2026 May 21.

    PubMed 42166612

  • 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 Apr;341:104546. doi: 10.1016/j.resp.2026.104546. Epub 2026 Jan 27.

    PubMed 41615840

  • Leahy MG, MacNamara JP, Tomlinson AR, Wakeham DJ, Brazile TL, Abulimiti A, Lutz KC, Levine BD, Sarma S, Babb TG, Balmain BN. Exercise-induced arterial hypoxaemia in patients with heart failure with preserved ejection fraction. J Physiol. 2025 Nov;603(22):7383-7396. doi: 10.1113/JP289362. Epub 2025 Sep 7.

    PubMed 40914966

  • 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.

    PubMed 40578265

  • 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.

    PubMed 39051098

  • 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.

    PubMed 36524474

Questions about this trial

What is this clinical trial studying?

A study testing Exercise training in people with Heart Failure, Diastolic, run by University of Texas Southwestern Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Aerobic fitness (time frame: 4 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04068844, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2026.

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