The Effect of Adiposity on Muscle and Microvascular Function in HFpEF

March 23, 2026 updated by: Christopher Hearon, University of Texas Southwestern Medical Center

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
95

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Group 1: Patients with HFpEF

- UTSW HFpEF clinic: lead by Dr. Ambarish Pandey

Group 2: non-HFpEF controls

  • subjects in the UTSW volunteer research registry who meet inclusion/exclusion criteria
  • community outreach (emailers, word of mouth, referrals)

Description

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.

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
HFpEF and Obesity Group
Patients with HFpEF (heart failure with preserved ejection fraction) and diabetes will undergo standard of care treatment using the most appropriate second-generation anti-diabetic drug that induces clinically significant weight loss after completing baseline (pre) testing.
Drug: Weight loss SOC Treatment with second generation anti-diabetic medications
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.
Control Group (Non-HFpEF and Obesity)
Controls matched for age and hypertension

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
Pre intervention (Day 1)
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)
Post intervention (Post Day 1)
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
Pre intervention (Day 2)
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
Post intervention (Day 2)
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)
Pre intervention (Day 3)
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
Pre intervention (Day 3)
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
Post intervention (Day 3)
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
Post intervention (Day 3)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Pre intervention (Day1)
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
Post intervention (Day 1)
Blood volume measurement
Time Frame: Pre intervention (Day1)
The carbon monoxide rebreathe technique will be performed to measure blood volume
Pre intervention (Day1)
Blood volume measurement
Time Frame: Post intervention (Day 1)
The carbon monoxide rebreathe technique will be performed to measure blood volume
Post intervention (Day 1)
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
Pre intervention (Day 2)
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
Pre intervention (Day 2)
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
Post intervention (Day2)
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
Post intervention (Day2)
Body composition
Time Frame: Pre intervention (Day 0)
measured using dual xray absorptiometry (DEXA) to get lean mass, muscle mass, body fat percentage
Pre intervention (Day 0)
Body composition
Time Frame: Post intervention (Day 1)
measured using dual xray absorptiometry (DEXA) to get lean mass, muscle mass, body fat percentage
Post intervention (Day 1)
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
Pre intervention (Day 2)
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
Post intervention (Day 2)

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Texas Southwestern Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Christopher M Hearon Jr, PhD, University of Texas Southwestern Medical Center

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 10, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 31, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 8, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 16, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 23, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STU-2024-0279

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

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