The Effect of Adiposity on Muscle and Microvascular Function in HFpEF

NCT06930495 | Enrolling By Invitation

• 1 other identifier: STU-2024-0279
• Study Type: observational
• Target: 95
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Define the mechanisms by which adiposity impairs exercise hemodynamics, microvascular function, and oxygen transport/utilization in patients with HFpEF.
2. 2.Determine if intensive medically directed weight loss can reduce microvascular inflammation and normalize exercise hemodynamics.
3. 3.Quantify the effect of medically directed weight loss on skeletal muscle function and catabolism.
4. 4.Perfusion of subcutaneous adipose tissue disrupts blood flow distribution and impairs muscle microvascular perfusion and exercise hemodynamics.
5. 5.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,
6. 6.Intensive weight loss will improve exercise hemodynamics, microvascular perfusion, and reduce muscular inflammation, and resistance training will augment these effects.

Conditions

Heart Failure With Preserved Ejection Fraction (HFPEF)

Keywords

HFpEF; Weight loss; adiposity; inflammation; RNA sequencing; skeletal muscle

Outcome Measures

Primary Outcomes (8)

• Peak muscle perfusion during exercise

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

  Pre intervention (Day 1)

• Peak muscle perfusion during exercise

  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

  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

  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

  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

  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

  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

  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 Outcomes (12)

• Vascular function - endothelium dependent vasodilation

  Pre intervention (Day1)

• Vascular function - endothelium dependent vasodilation

  Post intervention (Day 1)

• Blood volume measurement

  Pre intervention (Day1)

• Blood volume measurement

  Post intervention (Day 1)

• 2min walk endurance test

  Pre intervention (Day 2)

Study Arms (2)

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

Control Group (Non-HFpEF and Obesity)

Controls matched for age and hypertension

Interventions

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.

HFpEF and Obesity Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Weight Loss; Obesity; Inflammation

Condition Hierarchy (Ancestors)

Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Pathologic Processes

Study Officials

• Christopher M Hearon Jr, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 31, 2025
• First Posted: April 16, 2025
• Study Start: December 10, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 27, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)