Tesamorelin as an Adjunct to Exercise for Improving Physical Function in HIV (TRIUMPH)

People with HIV experience earlier impairments in physical function compared to people in the general population. They also exhibit an earlier presentation and more rapid development of frailty, a multisystemic syndrome of aging characterized by reduced activity, fatigue, slowness, weakness, and weight loss. While exercise can improve physical function in people with HIV, it is less effective in doing so than in the general population and is difficult to sustain in the long-term.

The goal of this clinical trial is to learn whether the medication tesamorelin will improve physical function and muscle health in adults with HIV when combined with exercise. Tesamorelin is a growth hormone-releasing hormone analogue that is FDA-approved to treat abdominal fat accumulation in people with HIV. While tesamorelin has also been shown to increase muscle mass and improve measures of muscle health, its effects on physical performance and muscle strength have not yet been evaluated.

During a 24-week intervention phase, half of participants will be randomly assigned to receive tesamorelin and half of participants will be randomly assigned to receive placebo (a look-alike substance that contains no drug). All participants also will engage in a home-based exercise intervention supervised by an exercise coach. During a subsequent 24-week extension phase, individuals will be monitored off study drug and supervised exercise, and be encouraged to continue to exercise independently.

The investigators will investigate effects of tesamorelin on physical function, muscle mass and quality, quality of life, and exercise adherence and self-efficacy. They also will evaluate whether effects of tesamorelin are maintained following treatment cessation. This study may identify an important strategy to improve how individuals aging with HIV function and feel with potential applications to other patient populations.

Study Overview

• Status: Recruiting
• Conditions: Frailty; Aging; HIV-1-infection; Abdominal Obesity; Impaired Physical Function
• Intervention / Treatment: Behavioral: Exercise; Drug: Placebo; Drug: Tesamorelin

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lindsay T. Fourman, MD; Phone Number: 617-643-4590; Email: lfourman@mgb.org
• Study Contact Backup: Name: Kristine M. Erlandson, MD; Phone Number: 303-724-4941; Email: kristine.erlandson@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado - Anschutz Medical Campus
      • Contact: Kristine M. Erlandson, MD; Phone Number: 3037244941; Email: kristine.erlandson@cuanschutz.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Julia Johnson; Phone Number: 617-724-5545; Email: jjohnson110@mgh.harvard.edu
      • Contact: Lindsay T Fourman, MD; Phone Number: 6176434590; Email: LFourman@mgb.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Men and women, 50-80 years old
2. Documented HIV infection on suppressive antiretroviral therapy for at least 1 year with HIV-1 RNA <200 copies/mL and CD4+ T cell count >200/µL 3
3. Sedentary lifestyle, defined as self-reported physical activity that breaks a sweat <3 days/week with no regular resistance exercise in the past 3 months
4. ≥1 Fried frailty criterion (weakness, slow gait speed, exhaustion, decreased physical activity, or unintentional weight loss as defined by specific thresholds)
5. Excess abdominal adiposity as indicated by at least one of the following elevated anthropometric measures assessed at Screen: (1) waist circumference ≥102 cm in non-Asian males (≥90 cm in Asian males) or ≥88 cm in non-Asian females (≥80 cm in Asian females); (2) waist-to-hip ratio ≥0.9 in males or ≥0.85 in females; (3) waist-to-height ratio ≥0.5 in males and females
6. Normal mammogram within 2 years (females ≤74 years old) or prostate specific antigen <4 ng/mL (males ≤70 years old) per U.S. Preventive Services Task Force (USPSTF) age-appropriate cancer screening guidelines
7. For females, postmenopausal defined as no menses for ≥12 months and anti-müllerian hormone (AMH) <20 pg/mL or history of bilateral oophorectomy at least 3 months ago
8. Provider approval to participate

Exclusion Criteria:

1. Use of tesamorelin or other growth hormone (GH)-based therapy within 6 months
2. Insulin-like growth factor 1 (IGF-1) z-score >2.0
3. HbA1c >8%
4. Active or suspected malignancy (with the exception of non-melanoma skin cancer) within 24 months
5. Supraphysiologic testosterone or corticosteroid exposure, or change in exogenous testosterone or corticosteroid dose within 3 months
6. Change in glucose-lowering medication (e.g., glucagon-like peptide-1 receptor agonists) within 3 months
7. Active or unstable coronary artery disease, chest pain suspicious for angina, or serious arrythmia
8. History of hypopituitarism, head irradiation, or other conditions known to affect the GH/IGF-1 axis
9. Known hypersensitivity to tesamorelin or mannitol
10. Acute or chronic illness judged by the investigator to represent a contraindication to study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Plus Exercise; Identical placebo given subcutaneously daily plus home-based semi-supervised exercise intervention	Behavioral: Exercise; Home-based semi-supervised exercise program; Drug: Placebo; Identical placebo injection given subcutaneously daily
Active Comparator: Tesamorelin Plus Exercise; Tesamorelin WR 1.28 mg given subcutaneously daily plus home-based semi-supervised exercise intervention	Behavioral: Exercise; Home-based semi-supervised exercise program; Drug: Tesamorelin; Tesamorelin WR 1.28 mg given subcutaneously daily; Other Names: Egrifta, TH9507, growth hormone-releasing hormone analogue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Repeated Chair Stand Time	Time to complete 10 repeated chair stands	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Standard and Modified Short Physical Performance Battery (SPPB)	Objective assessment of physical function that includes measures of balance, gait, and strength	Baseline to Week 24
Change in 1-Repetition Maximum Leg Press	Maximal weight that can be lifted by lower extremities once using correct form through full range of motion	Baseline to Week 24
Change in 400-Meter Walk Time	Time to walk 400 meters at the fastest pace possible	Baseline to Week 24
Change in Appendicular Lean Tissue Mass	Dual-energy x-ray absorptiometry (DXA) lean tissue mass in all four extremities	Baseline to Week 24
Change in Cross-Sectional Area of Trunk and Thigh Muscles	Computed tomography (CT) cross-sectional area of trunk and thigh muscles	Baseline to Week 24
Change in Exercise Adherence	FitBit (step count heart rate time), exercise log (movement type, repetitions, load, rate of perceived exertion)	Baseline to Week 24
Change in Tissue Density of Trunk and Thigh Muscles	Computed tomography (CT) attenuation of trunk and thigh muscles	Baseline to Week 24
Change in Visceral Adipose Tissue Cross-Sectional Area	Computed tomography (CT) cross-sectional area at L4	Baseline to Week 24
Change in Frailty Phenotype	Fried Frailty Phenotype score, scored from 0 to 5 with higher indicating worse	Baseline to Week 24
Change in Quality of Life	36-Item Short Form Health Survey (SF-36), scored from 0 to 100 with higher indicating better	Baseline to Week 24
Change in Exercise Self-Efficacy	Exercise Self-Efficacy Scale, scored from 0 to 100 with higher indicating better	Baseline to Week 24

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: University of Colorado, Denver
• Investigators: Principal Investigator: Lindsay T. Fourman, MD, Massachusetts General Hospital; Principal Investigator: Kristine M. Erlandson, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2025
• Primary Completion (Estimated): June 16, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: August 12, 2024
• First Submitted That Met QC Criteria: August 12, 2024
• First Posted (Actual): August 15, 2024

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nutrition Disorders; Overnutrition; Body Weight; Overweight; Obesity; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Frailty; Obesity, Abdominal; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise; tesamorelin; Ghrelin
• Other Study ID Numbers: 2024P001703

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No