Clinical trial NCT06930495: The Effect of Adiposity on Muscle and Microvascular Function in HFpEF
Official title: The Effect of Adiposity on Muscle and Microvascular Function in HFpEF
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Failure With Preserved Ejection Fraction (HFPEF)
Keywords: HFpEF
Weight loss
adiposity
inflammation
RNA sequencing
skeletal muscle
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2025-04-16
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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)

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

Eligibility criteria: 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.

Primary outcomes:
measure: Peak muscle perfusion during exercise
timeFrame: Pre intervention (Day 1)
measure: Peak muscle perfusion during exercise
timeFrame: Post intervention (Post Day 1)
measure: Single cell RNA sequencing of skeletal muscle
timeFrame: Pre intervention (Day 2)
measure: Single cell RNA sequencing of skeletal muscle
timeFrame: Post intervention (Day 2)
measure: Muscle to fat ratio of leg
timeFrame: Pre intervention (Day 3)
measure: Peak change in microvascular perfusion from rest to exercise
timeFrame: Pre intervention (Day 3)
measure: Muscle to fat ratio of leg
timeFrame: Post intervention (Day 3)
measure: Peak change in microvascular perfusion from rest to exercise
timeFrame: Post intervention (Day 3)
Secondary outcomes:
measure: Vascular function - endothelium dependent vasodilation
timeFrame: Pre intervention (Day1)
measure: Vascular function - endothelium dependent vasodilation
timeFrame: Post intervention (Day 1)
measure: Blood volume measurement
timeFrame: Pre intervention (Day1)
measure: Blood volume measurement
timeFrame: Post intervention (Day 1)
measure: 2min walk endurance test
timeFrame: Pre intervention (Day 2)
measure: Hand grip strength
timeFrame: Pre intervention (Day 2)
measure: 2min walk endurance test
timeFrame: Post intervention (Day2)
measure: Hand grip strength
timeFrame: Post intervention (Day2)
measure: Body composition
timeFrame: Pre intervention (Day 0)
measure: Body composition
timeFrame: Post intervention (Day 1)
measure: Apnea hypopnea index
timeFrame: Pre intervention (Day 2)
measure: Apnea hypopnea index
timeFrame: Post intervention (Day 2)
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Christopher M Hearon Jr, PhD
role: PRINCIPAL_INVESTIGATOR
References: