The Effect of Adiposity on Muscle and Microvascular Function in HFpEF

NCT ID: NCT06930495

Last Updated: 2025-07-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-12-10

Study Completion Date

2026-06-01

Brief Summary

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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.

Detailed Description

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

Conditions

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Heart Failure With Preserved Ejection Fraction (HFPEF)

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Weight loss SOC Treatment with second generation anti-diabetic medications

Intervention Type 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.

Control Group (Non-HFpEF and Obesity)

Controls matched for age and hypertension

No interventions assigned to this group

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Texas Southwestern Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Christopher Hearon

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Christopher M Hearon Jr, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center

Locations

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University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Sarah L Hissen, PhD

Role: CONTACT

214-345-8841

Christopher M Hearon Jr, PhD

Role: CONTACT

214-345--4624

Other Identifiers

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STU-2024-0279

Identifier Type: -

Identifier Source: org_study_id

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