HIV-1-infection, Frailty, Impaired Physical Function, Abdominal Obesity, Aging
Conditions
Brief summary
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.
Interventions
DRUGTesamorelin
Tesamorelin WR 1.28 mg given subcutaneously daily
DRUGPlacebo
Identical placebo injection given subcutaneously daily
BEHAVIORALExercise
Home-based semi-supervised exercise program
Sponsors
University of Colorado, Denver
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
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. Waist circumference ≥102 cm in men and ≥88 cm in women 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Repeated Chair Stand Time | Baseline to Week 24 | Time to complete 10 repeated chair stands |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Standard and Modified Short Physical Performance Battery (SPPB) | Baseline to Week 24 | Objective assessment of physical function that includes measures of balance, gait, and strength |
| Change in 1-Repetition Maximum Leg Press | Baseline to Week 24 | Maximal weight that can be lifted by lower extremities once using correct form through full range of motion |
| Change in 400-Meter Walk Time | Baseline to Week 24 | Time to walk 400 meters at the fastest pace possible |
| Change in Appendicular Lean Tissue Mass | Baseline to Week 24 | Dual-energy x-ray absorptiometry (DXA) lean tissue mass in all four extremities |
| Change in Cross-Sectional Area of Trunk and Thigh Muscles | Baseline to Week 24 | Computed tomography (CT) cross-sectional area of trunk and thigh muscles |
| Change in Frailty Phenotype | Baseline to Week 24 | Fried Frailty Phenotype score, scored from 0 to 5 with higher indicating worse |
| Change in Quality of Life | Baseline to Week 24 | 36-Item Short Form Health Survey (SF-36), scored from 0 to 100 with higher indicating better |
| Change in Exercise Self-Efficacy | Baseline to Week 24 | Exercise Self-Efficacy Scale, scored from 0 to 100 with higher indicating better |
| Change in Exercise Adherence | Baseline to Week 24 | FitBit (step count heart rate time), exercise log (movement type, repetitions, load, rate of perceived exertion) |
| Change in Tissue Density of Trunk and Thigh Muscles | Baseline to Week 24 | Computed tomography (CT) attenuation of trunk and thigh muscles |
| Change in Visceral Adipose Tissue Cross-Sectional Area | Baseline to Week 24 | Computed tomography (CT) cross-sectional area at L4 |
Countries
United States
Contacts
Primary ContactLindsay T. Fourman, MD
Backup ContactKristine M. Erlandson, MD
Outcome results
None listed