A Study to Improve Skeletal Muscle in Veterans With HIV

Phase 4

Not yet recruiting

• Conditions: HIV; Obesity

• Registration Number: NCT06845046
• Lead Sponsor: VA Office of Research and Development

Brief Summary

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.

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 Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-19
• Study First Submitted QC: 2025-02-19
• Study First Posted: 2025-02-25
• Last Update Submitted: 2025-02-26
• Last Update Posted: 2025-03-03
• Study Start: 2025-07-01
• Primary Completion: 2029-06-29
• Study Completion: 2029-06-29

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 70

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Primary Outcome Measures

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

Trial Locations

Locations (1)

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN; 🇺🇸 Nashville, Tennessee, United States