A Study to Improve Skeletal Muscle in Veterans With HIV

A Randomized Trial to Optimize Skeletal Muscle While Reducing Adiposity in Veterans With HIV

The Department of Veterans Affairs is the largest single provider of medical care to people with HIV in the United States. The condition of excess lipid within and around muscle, termed myosteatosis, predisposes Veterans to physical function decline, frailty, disability, and cardiometabolic diseases such as diabetes and cardiovascular disease. In the investigators current Merit supported cohort, the investigators found that 36% of Veterans with treated HIV and obesity have "myosteatotic type obesity". Based on the investigators findings, the investigators have designed a multipronged integrated intervention that combines: 1) dietary replacement of saturated with unsaturated fats; 2) administration of L-carnitine and omega-3 fatty acid supplementation; and 3) targeted resistance exercise training.

Study Overview

• Status: Recruiting
• Conditions: Obesity; HIV
• Intervention / Treatment: Other: Control Diet; Dietary supplement: w-3 fatty acid; Dietary supplement: L-carnitine

Detailed Description

The Department of Veterans Affairs is the largest single provider of medical care to people with HIV in the United States. With the advances achieved in antiretroviral therapy (ART), Veterans with HIV now survive decades. However, this success is tempered by the rising burden of obesity now affecting 78% of Veterans. Defects in adipose tissue lipid storage and regulation are hallmarks of both treated HIV and obesity, which leads to a high degree of ectopic fat infiltrating organs and tissues such as skeletal muscle. The condition of excess lipid within and around muscle, termed myosteatosis, predisposes Veterans to physical function decline, frailty, disability, and cardiometabolic diseases such as diabetes and cardiovascular disease. In the investigators current Merit supported cohort, the investigators found that 36% of Veterans with treated HIV and obesity have "myosteatotic type obesity". Further, the investigators found that high ectopic fat accumulation in muscle (quantified by CT imaging of skeletal muscle density) is associated with reduced mitochondrial oxidative capacity, greater inflammation, and impaired muscle glucose tolerance and insulin sensitivity. Hence the quality of muscle is just as important as the quantity of muscle. However, this important phenomenon has received little attention, especially in Veterans with HIV. Indeed, the need to target mobilizing and metabolizing skeletal muscle ectopic fat while preserving/increasing the total amount of skeletal muscle is most often overlooked and represents a major research gap and unmet clinical need. From the investigators current Merit Award funded study, the investigators have an established collaboration of experienced VA researchers with expertise in HIV and immunology, human nutrition and metabolism, endocrinology, radiology and imaging science, and muscle physiology. Based on the investigators findings, the investigators have designed a multipronged integrated intervention that combines: 1) dietary replacement of saturated with unsaturated fats; 2) administration of L-carnitine and omega-3 fatty acid supplementation; and 3) targeted resistance exercise training. This evidence-based intervention is designed to: a) increase lipid flux by facilitating the transfer of long-chain fatty acids into muscle mitochondria for -oxidation; b) decrease muscle proteolysis; and c) lessen insulin resistance and inflammation. Using a mixed 2x4 factorial design trial design in a cohort of 60 Veterans who have HIV and obesity, this study will determine the main and interaction effects of the multi-pronged intervention on: skeletal muscle density, mitochondrial oxidative capacity, and fatty acid oxidation (Aim 1); glucose tolerance, insulin sensitivity, and inflammation (Aim 2); and cardiopulmonary exercise tolerance and physical function (Aim 3). Obesity in Veterans with treated HIV is a heterogeneous condition. The investigators current Merit research shows myosteatotic obesity is a distinct condition from visceral or steatotic or sarcopenic obesity, affected by different clinical factors. The investigators findings to date provide the foundation for a novel evidence-based intervention that has the potential for significant clinical impact on Veterans, including and beyond those with HIV. This proposal meets VA-ORD priorities to improve health behaviors, focus on underserved Veterans, and provide precision care.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Heidi J Silver, PhD; Phone Number: (615) 875-9355; Email: heidi.j.silver@vumc.org
• Study Contact Backup: Name: John R Koethe, MD; Phone Number: (615) 873-6188; Email: john.koethe@va.gov

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212-2637
      • Recruiting
      • Tennessee Valley Healthcare System Nashville Campus, Nashville, TN
      • Principal Investigator: Heidi J Silver, PhD
      • Contact: Patrick M Lynch; Phone Number: 615-873-6927; Email: Patrick.Lynch2@va.gov
      • Contact: Geraldine M Freddie; Phone Number: (615) 873-8694; Email: Geraldine.Freddie@va.gov
      • Principal Investigator: John R Koethe, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Veteran
• HIV+
• antiretroviral therapy = integrase strand transfer inhibitor for at least 3 months
• HIV-1 RNA <50 copies/ml
• age = 20 yrs
• BMI 28-50 kg/m2

Exclusion Criteria:

• unstable body weight (gain or loss > 5% over past 3 months)
• diagnosed mitochondrial disorder
• diagnosed type 1 or type 2 diabetes
• use of metformin or other anti-diabetic agents for pre-diabetes
• hemoglobin A1c of >6.5% at screening visit
• inflammatory conditions or chronic corticosteroid use
• stage 3 or greater kidney disease
• dietary or herbal supplements known to affect body weight, muscle mass, or immune function
• MRI incompatibility
• inability to perform physical function tests due to anatomical limitations
• contradictions to CPET such as exercise-induced ischemia or supplemental oxygen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Diet; Diet high in unsaturated fat	Other: Control Diet; Control Diet high in unsaturated fat
Experimental: Diet + w-3 fatty acids; Diet high in unsaturated fat plus omega-3 fatty acid supplement	Other: Control Diet; Control Diet high in unsaturated fat; Dietary supplement: w-3 fatty acid; omega-3 fatty acid supplement
Experimental: Diet + L-Carnitine; Diet high in unsaturated fat plus L-carnitine supplement	Other: Control Diet; Control Diet high in unsaturated fat; Dietary supplement: L-carnitine; L-carnitine supplement
Experimental: Diet + w-3 fatty acids + L-carnitine; Diet high in unsaturated fat plus omega-3 fatty acid supplement plus L-carnitine supplement	Other: Control Diet; Control Diet high in unsaturated fat; Dietary supplement: w-3 fatty acid; omega-3 fatty acid supplement; Dietary supplement: L-carnitine; L-carnitine supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myosteatosis	CT quantified abdominal skeletal muscle density	Week 24 and 44
MixedMeal GTT	IV Glucose tolerance testing after consumption of BOOST as a meal substitute	Week 24 and 44
Physical Function	Physical Function Testing using Hand Grip Strength Dynamometer	Week 24 and 44

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Heidi J Silver, PhD, Tennessee Valley Healthcare System Nashville Campus, Nashville, TN; Principal Investigator: John R Koethe, MD, Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2025
• Primary Completion (Estimated): June 29, 2029
• Study Completion (Estimated): June 29, 2029

Study Registration Dates

• First Submitted: February 19, 2025
• First Submitted That Met QC Criteria: February 19, 2025
• First Posted (Actual): February 25, 2025

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 25, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: HIV; obesity; dietary supplement; skeletal muscle
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Obesity
• Other Study ID Numbers: INFA-009-24F

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