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NCT Number: NCT07223242

Tailored Exercise Training Study Among Adults With HFpEF

Heart failure with preserved ejection fraction (HFpEF) is associated with a high morbidity and mortality burden. There are limited pharmacological options available for the treatment of HFpEF. Exercise intolerance (EI) is the cardinal symptom of HFpEF, which manifests as dyspnea and fatigue. EI leads to functional deconditioning and reduced quality of life (QOL), both of which elevate risk of death and hospitalization in patients with HFpEF. Supervised exercised training is associated with improvements in exercise capacity and QOL in adults with HFpEF. However, supervised exercise has not been widely utilized for the treatment of HFpEF due to logistical and fiscal barriers.

This study will investigate the effects of a remote exercise training intervention on exercise capacity and skeletal muscle composition in patients with HFpEF, or those at risk for it. In addition, it will compare four different lifestyle interventions for their effects on exercise capacity.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

University of Texas Southwestern Medical Center

Dallas, Texas, 75209, United States

Location status: Recruiting

Location contact

Ambarish Pandey, MD

CONTACT

[email protected]

214-645-9868

About this study

Heart failure (HF) portends substantial morbidity, mortality, and health care costs in the United States and the prevalence of heart failure with preserved ejection fraction (HFpEF) relative to HF with reduced ejection fraction (HFrEF) has been increasing. HFpEF is associated with a high morbidity and mortality burden. There are limited pharmacological options available for the treatment of HFpEF. It is now recognized as a systemic, multi-organ, geriatric syndrome, with exercise intolerance (EI) and functional impairment as the key clinical manifestations. EI leads to functional deconditioning and reduced quality of life (QOL), both of which elevate risk of death and hospitalization in patients with HFpEF. Supervised exercised training is associated with improvements in exercise capacity and QOL in adults with HFpEF. However, supervised exercise has not been widely utilized for the treatment of HFpEF due to logistical and fiscal barriers.

This study will investigate the effects of a remote exercise training intervention on exercise capacity and skeletal muscle composition in patients with HFpEF, or those at risk for it. In addition, it will compare the effects of four different lifestyle interventions on exercise capacity.

The study will be carried out in two phases. In Phase I, 120 participants will undergo three months of home-based moderate-intensity continuous training (MCT), using tailored exercise videos on a mobile or tablet. Participants will also have weekly virtual meetings with a coach to discuss their progress. This will be followed by 3 months of no intervention, to assess the effects of detraining.

In Phase II (at the 6-month mark), 100 participants will be randomized to one of four extended training strategies for 3 months -(i) MCT alone; (ii) MCT plus resistance training; (iii) MCT plus weight loss, or (iv) MCT plus resistance training and weight loss.

The co-primary outcomes are (1) peak VO2, and (2) short physical performance battery score. In addition, participants will undergo CT chest/abdomen/pelvis at 3 months and 6 months to assess change in skeletal muscle composition with MCT

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Age>= 18 yrs
  • LVEF (Left Ventricular Ejection Fraction) >= 50%
  • History of HFpEF or at risk of HFpEF
  • HFpEF diagnosis based on:- -HF hospitalization within 12 months-
  • NT-proBNP >360 pg/mL
  • Risk of HFpEF based on:-
  • >2 risk factors (h/o diabetes, hypertension, obesity, physical inactivity by self-report)
  • SPPB < 10 or VO2<60th percentile
  • BMI >=28 (for randomization in phase II)
  • Able to use cell phone and mobile application

Exclusion criteria

  • Hospitalization 1 month prior to baseline visit
  • History of recurrent falls
  • eGFR (Estimated Glomerular Filtration Rate) <20ml/min/1.73m
  • Active changes in HF therapies over 2 weeks prior to baseline visit
  • Inability participate in exercise training therapy
  • Inability to perform CPET (Cardiopulmonary Exercise Testing) testing
  • Severe left side valvular heart disease
  • End stage pulmonary disease, requiring continuous supplemental oxygen
  • Major surgery within 3 months of screening or major elective surgery during the duration of the study.
  • Unstable weight defined by >5% change in body weight in last 30 days before first study visit.
  • Pregnancy

Treatment and study plan

Moderate-intensity Continuous Training (MCT)

Behavioral

Tailored moderate-intensity exercise training video with weekly virtual meetings with a coach

Resistance training

Behavioral

Resistance training videos assigned to patient

Weight loss

Drug

Initiation/intensification of weight loss medications, such as semaglutide or tirzepatide

Primary outcomes

  1. Peak Exercise Oxygen Uptake (VO2peak)

    Time frame: Baseline, 3months, 6months, and 9months

    VO2peak indexed to body weight (mL/kg/min) will be the co-primary outcome for the trial. VO2peak is a gold-standard measure of aerobic exercise capacity and will be measured by maximal exercise test using a previously established ergometer protocol

  2. Short Physical Performance Battery (SPPB)

    Time frame: Baseline, 3months, 6months, and 9months

    SPPB will be a co-primary outcome for the trial. Score ranges from 0 to 12, with 0 indicating the worst performance and 12 indicating the best.

Secondary outcomes

  1. Kansas City Cardiomyopathy Questionnaire 12 (KCCQ-12)

    Time frame: Baseline, 3months, 6months, and 9months

    Health-related quality of life will be assessed using the KCCQ-12 questionnaire. This is a self-administered questionnaire that assesses a patient's perception of their heart failure with regard to the psychological, physical, and socioeconomic aspects of life. Scores range from 0 to 100, where 0 indicates the worst possible health status and 100 indicates the best.

  2. 6 Minute Walk Distance (6MWD)

    Time frame: Baseline, 3months, 6months, and 9months

    6MWD is a simple and well-validated measure of submaximal exercise capacity and does not require any exercise equipment or advanced training for technicians

  3. General Quality of Life - EQ-5D-5L

    Time frame: Baseline, 3months, 6months, and 9months

    Change in general health-related quality of life assessed using the EuroQol 5 Dimension 5 Level (EQ-5D-5L) instrument. The EQ-5D-5L uses a descriptive system to measure health-related quality of life across five key dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on five levels of severity-ranging from no problems (Level 1) to extreme problems or inability to function (Level 5). A respondent's answers generate a five-digit health state profile that reflects their unique combination of responses (e.g., 12345), representing one of 3,125 possible health states. This descriptive system enables consistent and standardized assessment of an individual's health status.

  4. Thirty Second Chair Test

    Time frame: Baseline, 3months, 6months, and 9months

    The 30-second chair stand test measures lower-body strength and endurance by counting how many times a person can stand up from a chair and sit down within 30 seconds.

  5. Fried Frailty Phenotype

    Time frame: Baseline, 3months, 6months, and 9months

    The Fried frailty phenotype defines frailty based on five criteria-unintentional weight loss, exhaustion, weakness, slow walking speed, and low physical activity. Each criterion met adds one point to the total score. The Fried Frailty scale has a score range of 0 to 5. A score of 0 means the person is robust or not frail, a score of 1 or 2 indicates pre-frailty (intermediate risk), and a score of 3 or more means the person is considered frail.

  6. Resting cardiac output

    Time frame: Baseline, 3months, 6months, and 9months

    Assess with echocardiography to measure stroke volume and heart rate during rest

  7. Exercise cardiac output

    Time frame: Baseline, 3months, 6months, and 9months

    Assess with echocardiography to measure stroke volume and heart rate responses with graded physical stress.

  8. Intramyocellular fat

    Time frame: Baseline, 3months, 6months, and 9months

    Assessed with non-contrast CT scans of the chest, abdomen, and pelvis. These scans will be used to measure the radiodensity of muscle tissue, quantified in Hounsfield Units (HU). Skeletal muscle tissue is assigned a range of HU values (-29 to +150). Higher fat content lowers the overall muscle density, resulting in lower HU values

  9. Intermuscular Adipose Tissue (IMAT)

    Time frame: Baseline, 3months, 6months, and 9months

    Assessed with non-contrast CT scans of the chest, abdomen, and pelvis. These scans quantify intermuscular adipose tissue (IMAT) using the Hounsfield unit (HU) scale, where IMAT is classified as fat density within a range of -250 to -30 HU. The area of fat deposits is then quantified in square centimeters (cm^2)

  10. Subcutaneous adiposity deposits

    Time frame: Baseline, 3months, 6months, and 9months

    Assessed with non-contrast CT scans of the chest, abdomen, and pelvis. These scans quantify fat deposits using the Hounsfield unit (HU) scale, where fat is defined as a density within a range of -250 to -30 HU. The area of fat deposits is then quantified in square centimeters (cm^2)

  11. Visceral Adiposity Deposits

    Time frame: Baseline, 3months, 6months, and 9months

    Assessed with non-contrast CT scans of the chest, abdomen, and pelvis. These scans quantify fat deposits using the Hounsfield unit (HU) scale, where fat is defined as a density within a range of -250 to -30 HU. The area of fat deposits is then quantified in square centimeters (cm^2)

  12. Pericardial Adiposity Deposits

    Time frame: Baseline, 3months, 6months, and 9months

    Assessed with non-contrast CT scans of the chest, abdomen, and pelvis. These scans quantify fat deposits using the Hounsfield unit (HU) scale, where fat is defined as a density within a range of -250 to -30 HU. The area of fat deposits is then quantified in square centimeters (cm^2)

  13. Lower Body Adiposity Deposits

    Time frame: Baseline, 3months, 6months, and 9months

    Assessed with non-contrast CT scans of the chest, abdomen, and pelvis. These scans quantify fat deposits using the Hounsfield unit (HU) scale, where fat is defined as a density within a range of -250 to -30 HU. The area of fat deposits is then quantified in square centimeters (cm^2)

  14. E/e': Ratio of early mitral inflow velocity (E) to early diastolic mitral annular velocity (e')

    Time frame: Baseline, 3months, 6months, and 9months

    Exercise echocardiography to measure E/e' ratio to assess left ventricular filling pressures at rest and during graded physical stress

  15. Left atrial reservoir strain

    Time frame: Baseline, 3months, 6months, and 9months

    Assessed using echocardiography at rest and during graded physical stress

  16. Left ventricular global longitudinal strain (LV GLS)

    Time frame: Baseline, 3months, 6months, and 9months

    Assessed using echocardiography at rest and during graded physical stress

  17. GAD 7 score

    Time frame: Baseline, 3months, 6months, and 9months

    Change in anxiety symptoms assessed using the Generalized Anxiety Disorder-7 (GAD-7) scale. Total scores range from 0 to 21, with higher scores indicating more severe anxiety symptoms.

  18. PHQ 9 score

    Time frame: Baseline, 3months, 6months, and 9months

    This is a self-administered questionnaire that assesses the severity of depressive symptoms. The PHQ-9 (Patient Health Questionnaire-9) ranges from 0 to 27, with higher scores indicating more severe depressive symptoms.

  19. NT-proBNP

    Time frame: Baseline, 3months, 6months, and 9months

    Serum level of NT-proBNP (N-terminal pro-brain natriuretic peptide), a biomarker that reflects cardiac stress.

  20. High-sensitivity troponin I

    Time frame: Baseline, 3months, 6months, and 9months

    Serum high-sensitivity troponin I reflects ongoing low-grade myocardial injury and is a marker of disease severity and prognosis in chronic heart failure.

Sponsors and collaborators

Lead sponsor

University of Texas Southwestern Medical Center

Other

Registry information

Acronym: TEXPEF

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Oct 31, 2025
Registry last updated
Oct 31, 2025

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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