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Enrolling by Invitation

NCT Number: NCT06930495

The Effect of Adiposity on Muscle and Microvascular Function in HFpEF

This project is an observational study in patients with heart failure with preserved ejection fraction (HFpEF) who are candidates for treatment with weight loss medication to manage obesity or diabetes as part of their standard clinical care. This study will include multiple experimental visits before and after treatment (minimum 7 percent weight loss, between 9-12 months) to understand how increased adiposity and inflammation effects skeletal muscle and cardiovascular health and function and to examine the effect of medically directed weight loss on skeletal muscle health and exercise tolerance.

The objective of this study is to

1. Define the mechanisms by which adiposity impairs exercise hemodynamics, microvascular function, and oxygen transport/utilization in patients with HFpEF. 2. Determine if intensive medically directed weight loss can reduce microvascular inflammation and normalize exercise hemodynamics. 3. Quantify the effect of medically directed weight loss on skeletal muscle function and catabolism.

Hypotheses

1. Perfusion of subcutaneous adipose tissue disrupts blood flow distribution and impairs muscle microvascular perfusion and exercise hemodynamics. 2. Extramyocellular muscular lipid deposition and microvascular endothelial inflammation is associated with reduced capillarity and impaired microvascular perfusions, while intramyocellular triglyceride content is associated with poor skeletal muscle oxidative capacity, 3. Intensive weight loss will improve exercise hemodynamics, microvascular perfusion, and reduce muscular inflammation, and resistance training will augment these effects.

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Key information

Conditions

Heart Failure With Preserved Ejection Fraction (HFpEF) Body Weight Body Weight Changes Inflammation Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathologic Processes Pathological Conditions, Signs and Symptoms Signs and Symptoms Weight Loss

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

About this study

Objective one will also include a cross-sectional comparison between HFpEF patients before treatment and non-HFpEF controls matched for age and hypertension

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

Group 1: Patients with HFpEF

  • Diagnosis of heart failure or clear heart failure hospitalization
  • Stable ejection fraction > 0.50
  • Objective evidence of elevated left ventricular filling pressure by one of the following i) pulmonary capillary wedge pressure ≥25 mmHg during supine cardiopulmonary exercise testing or ii) a change in pulmonary capillary wedge pressure of >15 mmHg during upright exercise
  • Must be candidates for pharmacological incretin-based directed intensive weight loss therapies as part of their SOC
  • BMI>32kg/m2
  • ≥45 years old
  • Incretin naïve for 6 months

Group 2: Non-HFpEF controls

  • Adults who do not have heart failure with preserved ejection fraction
  • Age ≥ 18 years

Exclusion criteria

Group 1

  • Prior history of reduced ejection fraction (<50%)
  • Infiltrative cardiomyopathy
  • NYHA Class IV chronic heart failure
  • Left bundle branch block
  • Unstable coronary artery disease
  • Uncontrolled arrhythmia
  • CKD 4 or higher
  • Currently taking incretin-based drugs (SGL2, GLP1)
  • Severe valvular heart disease
  • BMI > 50kg/m2
  • Other debilitating illness that would preclude participation
  • Any contra-indication to MRI
  • Any contra-indication to muscle biopsies.

Group 2

  • Age < 18 years
  • BMI > 50 kg/m2
  • Atrial fibrillation with poorly controlled heart rate
  • PDE5 inhibitor use
  • Severe valvular disease
  • Severe COPD
  • CKD 4 or higher
  • Currently taking incretin-based drugs (SGL2, GLP1)
  • Any contra-indication to MRI
  • Any contra-indication to muscle biopsies.

Treatment and study plan

Weight loss SOC Treatment with second generation anti-diabetic medications

Drug

To determine the best incretin-based drug for the treatment [done as part of regular standard of care (SOC) treatment], participants will go to UTSW weight wellness clinic and undergo a comprehensive history and physical exam to evaluate their overall health. This information is used to create an individualized approach to the participants weight loss regimen. As part of the regimen, participants will receive guidance on initiating lifestyle modifications including diet and exercise and may be referred to a clinical psychologist for evaluation and management of factors like stress, anxiety and depression, and exercise which may influence their health behaviors and body weight.

Primary outcomes

  1. Peak muscle perfusion during exercise

    Time frame: Pre intervention (Day 1)

    Peak muscle perfusion (Aβ) during exercise will be assessed by Contrast enhanced ultrasound (CEU)

  2. Peak muscle perfusion during exercise

    Time frame: Post intervention (Post Day 1)

    Peak muscle perfusion (Aβ) during exercise will be assessed by Contrast enhanced ultrasound (CEU)

  3. Single cell RNA sequencing of skeletal muscle

    Time frame: Pre intervention (Day 2)

    Skeletal muscle biopsies will be taken from the vastus lateralis using the modified Bergstrom technique and immediately prepared for single cell RNA sequencing. Samples will be digested, filtered, washed and resuspended in freezing media and checked for concentration and viability before single cell RNA sequencing is performed

  4. Single cell RNA sequencing of skeletal muscle

    Time frame: Post intervention (Day 2)

    Skeletal muscle biopsies will be taken from the vastus lateralis using the modified Bergstrom technique and immediately prepared for single cell RNA sequencing. Samples will be digested, filtered, washed and resuspended in freezing media and checked for concentration and viability before single cell RNA sequencing is performed

  5. Muscle to fat ratio of leg

    Time frame: Pre intervention (Day 3)

    MRI of the leg will be performed to acquire clear visualization of fasciae separating different muscle groups and thus allowing for quantification of intermuscular fat (muscle:fat ratio)

  6. Peak change in microvascular perfusion from rest to exercise

    Time frame: Pre intervention (Day 3)

    MRI of the leg will be performed utilizing the PIVOT sequence which will measure global and regional perfusion of blood to the muscles in the lower leg at rest and during exercise. the peak change will be reported as the change from baseline to peak exercise

  7. Muscle to fat ratio of leg

    Time frame: Post intervention (Day 3)

    MRI of the leg will be performed utilizing the PIVOT sequence which will measure the change in perfusion of blood to the muscles in the lower leg from rest to during exercise

  8. Peak change in microvascular perfusion from rest to exercise

    Time frame: Post intervention (Day 3)

    MRI of the leg will be performed utilizing the PIVOT sequence which will measure global and regional perfusion of blood to the muscles in the lower leg at rest and during exercise. the peak change will be reported as the change from baseline to peak exercise

Secondary outcomes

  1. Vascular function - endothelium dependent vasodilation

    Time frame: Pre intervention (Day1)

    A small ultrasound probe will be placed over the brachial artery and a small blood pressure cuff will be positioned on the lower arm, just below the elbow. Images of the vessel will be continuously recorded for 1 min (baseline) before the cuff is inflated to a high pressure (220mmHg) for 5minutes and immediately after the cuff is deflated for 3 minutes. The change in brachial artery diameter following deflation of cuff from baseline will represent a marker of vascular function

  2. Vascular function - endothelium dependent vasodilation

    Time frame: Post intervention (Day 1)

    A small ultrasound probe will be placed over the brachial artery and a small blood pressure cuff will be positioned on the lower arm, just below the elbow. Images of the vessel will be continuously recorded for 1 min (baseline) before the cuff is inflated to a high pressure (220mmHg) for 5minutes and immediately after the cuff is deflated for 3 minutes. The change in brachial artery diameter following deflation of cuff from baseline will represent a marker of vascular function

  3. Blood volume measurement

    Time frame: Pre intervention (Day1)

    The carbon monoxide rebreathe technique will be performed to measure blood volume

  4. Blood volume measurement

    Time frame: Post intervention (Day 1)

    The carbon monoxide rebreathe technique will be performed to measure blood volume

  5. 2min walk endurance test

    Time frame: Pre intervention (Day 2)

    Participants will be asked to walk on a flat surface back and forth between 2 cones for 2minutes. the total distance covered (in meters) during the 2-minutes will be recorded as a marker of endurance

  6. Hand grip strength

    Time frame: Pre intervention (Day 2)

    Participants will squeeze a handheld dynamometer as hard as they can to measure handgrip strength (in kg). This will be performed on both hands

  7. 2min walk endurance test

    Time frame: Post intervention (Day2)

    Participants will be asked to walk on a flat surface back and forth between 2 cones for 2minutes. the total distance covered (in meters) during the 2-minutes will be recorded as a marker of endurance

  8. Hand grip strength

    Time frame: Post intervention (Day2)

    Participants will squeeze a handheld dynamometer as hard as they can to measure handgrip strength (in kg). This will be performed on both hands

  9. Body composition

    Time frame: Pre intervention (Day 0)

    measured using dual xray absorptiometry (DEXA) to get lean mass, muscle mass, body fat percentage

  10. Body composition

    Time frame: Post intervention (Day 1)

    measured using dual xray absorptiometry (DEXA) to get lean mass, muscle mass, body fat percentage

  11. Apnea hypopnea index

    Time frame: Pre intervention (Day 2)

    Participants will be given an at home sleep apnea test that is incorporated into a wrist-based wearable that enables non-invasive tracking of sleep apnea burden.

    Sleep apnea will be determined from the apnea hypopnea index measured by the device. Apnea hypopnea index will be calculated as the average number of apneas or hypopneas that occurs per hour of sleep

  12. Apnea hypopnea index

    Time frame: Post intervention (Day 2)

    Participants will be given an at home sleep apnea test that is incorporated into a wrist-based wearable that enables non-invasive tracking of sleep apnea burden.

    Sleep apnea will be determined from the apnea hypopnea index measured by the device. Apnea hypopnea index will be calculated as the average number of apneas or hypopneas that occurs per hour of sleep

Sponsors and collaborators

Lead sponsor

University of Texas Southwestern Medical Center

Other

Registry information

Important dates

Study start
2024
Primary completion
2028
Study completion
2028
First posted
Apr 16, 2025
Registry last updated
Mar 27, 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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