Epicardial Adipose Tissue Composition and Heart Failure With Preserved Ejection Fraction

NCT07178145 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 302641
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

Brief Summary

This study seeks to develop improved cardiac MRI (CMR) methods to quantify epicardial adipose tissue (EAT) composition and to demonstrate the advantages of EAT composition imaging (a) in advancing the understanding of the relationship between EAT and heart failure with preserved ejection fraction (HFpEF) and (b) for understanding mechanisms of and guiding medical therapy in HFpEF. The investigators recently developed the first method for quantifying EAT FAC in human subjects, utilizing a rate-6 accelerated radial 2D multi-echo gradient-echo breathhold acquisition with a local low rank reconstruction. In this project the first specific aim is to develop a rapid free-breathing 3D EAT FAC MRI method that reduces motion-related artifacts, increases coverage, and facilitates higher spatial resolution and improved FAC reproducibility. The second specific aim is to show that EAT FAC is more strongly associated than EAT volume with cardiometabolic HFpEF. In this context, individuals with known or suspected HFpEF will undergo CMR, echocardiography, and other testing to (a) diagnose cardiometabolic HFpEF; (b) characterize features associated with the severity of HFpEF; and (c) assess EAT volume and FAC. The investigators will determine if EAT FAC is more strongly associated than EAT volume with HFpEF and with features associated with the severity of HFpEF. The third specific aim is to show, in the context of cardiometabolic HFpEF and pre-HFpEF, (a) that GLP-1 receptor agonism with semaglutide (SEMA) shifts the EAT FAC to a less proinflammatory profile and (b) that baseline EAT FAC is a stronger predictor than EAT volume of improved cardiovascular function due to SEMA. Cardiometabolic HFpEF and pre-HFpEF subjects will undergo echocardiography and CMR with EAT FAC at baseline and after 3 months to serve as a self-control. Subjects will then undergo repeat imaging 6 months after the initiation of SEMA. The change in FAC after treatment with SEMA will be compared to the change in FAC prior to SEMA. Data will be analyzed to show that SEMA changes EAT FAC, and that baseline EAT FAC is a stronger predictor than EAT volume of improvements in severity of HFpEF.

Conditions

Epicardial Adipose Tissue; Heart Failure Preserved Ejection Fraction

Keywords

HFpEF; Heart Failure preserved Ejection Fraction; Cardiac MRI; Epicardial Adipose Tissue; GLP-1; EAT FAC; cardiovascular function

Outcome Measures

Primary Outcomes (1)

• Epicardial adipose tissue (EAT) fatty acid composition (FAC)

  The longitudinal change in epicardial adipose tissue (EAT) fatty acid composition (FAC) \[quantified in terms of the fraction of saturated fatty acids (SFA) in units of %\] that occur after 6 months of treatment with semaglutide will be compared to the change in SFA that occurred during 3 month period prior to the initiation of semaglutide.

  Baseline, 3 months (self-control period), and 9-months (6 months post semaglutide treatment)

Secondary Outcomes (3)

• EAT Volume

  Baseline, 3months (self-control period), and 9-months (6 months post semaglutide treatment)

• Baseline Saturated Fatty Acid Composition of Epicaridal Adipose Tissue and Change in Myocardial Deformation

  Baseline, 3months (self-control period), and 9-months (6 months post semaglutide treatment)

• Baseline Saturated Fatty Acid Composition of Epicaridal Adipose Tissue and Change in diastolic dysfunction grade

  Baseline, 3months (self-control period), and 9-months (6 months post semaglutide treatment)

Study Arms (3)

3D EAT FAC CMR imaging

NO INTERVENTION

non-contrast MRI to debug/test 3D MRI techniques for quantifying EAT FAC

Imaging acquisition and medical condition overview

NO INTERVENTION

Will undergo Cardiac MRI, exercise echocardiography, 12 lead ECG, medical history review, bloodwork, physical exam, and optional stress cardiac MRI.

Imaging acquisition and GLP-1RA treatment

EXPERIMENTAL

Will undergo all testing before and after a 6-month treatment of GLP-1RA

Drug: GLP-1RA

Interventions

GLP-1RA DRUG

Receive 6 months of GLP-1RA (Semaglutide) treatment starting at 0.25mg once weekly and then the dose will be up titrated as tolerated every four weeks to once-weekly doses of 0.5, 1.0, 1.7, and 2.4 mg until a maximum dose of 2.4mg (or the subject's maximally tolerated dose, if the subject's maximally tolerated dose is \<2.4 mg) is reached after 16 weeks.

Imaging acquisition and GLP-1RA treatment

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years - 90 years;
• LVEF ≥ 50%;
• ≥ 2 risk factors for HFpEF or symptoms that could be related to HFpEF (e.g., dyspnea, orthopnea, paroxysmal nocturnal dyspnea, lower extremity edema, pulmonary edema, etc);
• Not currently being treated with GLP-1RA therapy.

You may not qualify if:

• Previously or currently reduced EF (\<50%), including heart transplant; (2) Obstructive un-revascularized coronary disease by coronary CT or invasive coronary angiography;
• MI/PCI/CABG within the past 6 months;
• Untreated severe stenotic or regurgitant valvular disease;
• Infiltrative cardiomyopathy (Fabry/HCM/sarcoid/amyloid, etc);
• Myocarditis;
• Claustrophobia/inability to tolerate MRI;
• Implants that are a contraindication for MRI or may negatively impact image quality (e.g. pacemakers and ICDs);
• Active systemic inflammatory disorder;
• Atrial fibrillation with rapid ventricular response at time of study; and
• Hemodynamic instability
• Pregnancy
• Prisoners
• Inability to provide informed consent
• allergy to gadolinium-based contrast agents
• Acute kidney injury

Sponsors & Collaborators

• University of Virginia: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

Related Publications (38)

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MeSH Terms

Conditions

Heart Failure, Diastolic

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases

Study Officials

• Amit Patel, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medard Ng

CONTACT

434-982-1058; HTN3U@uvahealth.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 23, 2025
• First Posted: September 17, 2025
• Study Start: November 20, 2025
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)