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NCT Number: NCT03775577

Exercise Intolerance in Heart Failure

The investigators are studying whether metabolic abnormalities in cardiac and skeletal muscle in patients with heart failure with preserved ejection fraction (HFpEF) are associated with debilitating exercise intolerance.

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Key information

Age range

21 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location status: Recruiting

Location contact

Tricia Steinberg, MSN

CONTACT

[email protected]

443-287-3469

About this study

This research is being done to better understand why patients with heart failure have difficulty exercising and performing some activities of daily living. Heart muscle and skeletal muscle (in the legs and arms) depend on normal metabolism (the conversion of foods to chemical fuel) to function properly. Investigators will measure metabolites in the heart and leg muscles, including the levels of high energy phosphates and lipids (fats) using magnetic resonance (MR) techniques. High-energy phosphates serve as a source of energy, which is used by the heart and skeletal muscle for contraction. Magnetic resonance uses magnetic fields to measure the levels of these substances.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients of either gender who are greater than 21 years of age (no upper age limit),
  • Permission of patient's clinical attending physician,
  • Previous clinical diagnosis of HF with current New York Heart Association (NYHA) Class II-III symptoms for at least 1 month,
  • Left ventricular ejection fraction (EF) >50% by echocardiography, MRI, CT or x-ray or nuclear ventriculography within prior 12 months,
  • Stable medical therapy for at least 30 days (no addition or removal or major (>100%) dose change of Renin-Angiotensin-Aldosterone System (RAAS) antagonists, beta-blockers, or calcium channel blockers for hypertension).

Exclusion criteria

  • Unable to understand the risks, benefits, and alternatives of participation and give meaningful consent,
  • Contraindications to MRI such as implanted metallic objects (pre-existing cardiac pacemakers, cerebral clips) or indwelling metallic projectiles,
  • Significant valvular abnormalities,
  • Pregnant women (women of childbearing potential will undergo blood or urine pregnancy testing),
  • History of clinical CAD or significant epicardial coronary disease (>50% stenosis) in major coronary artery by x-ray or CT angiography unless (a) the patient underwent prior successful revascularization with percutaneous coronary angioplasty within the prior three years and (b) there are no residual lesions of >50% on the most recent coronary angiographic study.
  • History of infiltrative cardiomyopathy or constrictive pericarditis,
  • Cor pulmonale,
  • Significant pulmonary disease,
  • Estimated glomerular filtration rate (eGFR) <20ml/min,
  • Any condition other than HF which could limit the ability to perform a 6MW or cardiopulmonary exercise test (CPET) test (e.g., critical peripheral vascular disease, significant orthopedic or neurological conditions),
  • Any diseases other than HF which are likely to significantly alter the patient's global perception of status or quality of life over a period of 6 months.
  • Significant peripheral vascular disease

Treatment and study plan

Primary outcomes

  1. Skeletal muscle mitochondrial function

    Time frame: Baseline

    Maximal oxidative capacity of leg muscle measured by 31P Magnetic Resonance Spectroscopy (MRS)

  2. Skeletal muscle energetic decline during exercise

    Time frame: Baseline

    Creatine phosphate rate of decline (umol/g/min) during plantar flexion exercise measured by 31P MRS

  3. Cardiac muscle energetics

    Time frame: Baseline

    Cardiac muscle phosphocreatine (PCr)/ adenosine triphosphate (ATP) and creatine kinase(CK) flux (umol/g/s) measured by 31P MRS

Secondary outcomes

  1. Six minute walk test

    Time frame: Six months

    Six minute walk distance (m)

  2. Cardiopulmonary exercise testing (CPET)

    Time frame: Six months

    Peak whole-body oxygen consumption rate during exercise

  3. Clinical heart failure outcome as assessed by number of hospitalizations

    Time frame: Two years

  4. Clinical heart failure outcome as assessed by time to cardiovascular death

    Time frame: Two years

  5. Clinical heart failure outcome as assessed by overall mortality

    Time frame: Two years

Study contacts

Contact information is provided by the study sponsor or research team.

Matthew Kauffman

CONTACT

[email protected]

443-287-3475

Tricia Steinberg, RN, MSN

CONTACT

[email protected]

443-287-3469

Sponsors and collaborators

Lead sponsor

Johns Hopkins University

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Official study title

Exercise Intolerance in Heart Failure: the Role of Altered Cardiac and Skeletal Muscle Energetics

Important dates

Study start
2017
Primary completion
2027
Study completion
2027
First posted
Dec 14, 2018
Registry last updated
Mar 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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