Clinical trial NCT01263717: Effects of Growth Hormone Releasing Hormone in HIV
Official title: Effects of Growth Hormone Releasing Hormone on Fat Redistribution, Cardiovascular Indices, and Growth Hormone Secretion in HIV Lipodystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
HIV Lipodystrophy
Keywords: HIV
lipodystrophy
tesamorelin
Egrifta
growth hormone releasing hormone
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2010-12-21
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: HIV-infection and its treatment are often associated with an increase in belly fat, as well as abnormal cholesterol and problems metabolizing sugar. People with HIV infection and increased belly fat often have decreased growth hormone (GH) levels. Low GH levels may contribute independently to increased belly fat and to increased cardiovascular risk through effects on sugar metabolism, inflammation, and other mechanisms. Tesamorelin, a growth hormone releasing hormone (GHRH) analogue, has been shown to to reduce belly fat in patients with HIV-associated abdominal fat accumulation. However, the effects of tesamorelin on fat accumulation in the liver and muscle, sugar metabolism, and cardiovascular health are not yet known. The current study is designed to determine the effects of tesamorelin treatment on fat accumulation in the muscle and liver, insulin sensitivity and sugar metabolism, and markers of cardiovascular health including blood vessel thickness (carotid intima media thickness \[cIMT\]) and markers of inflammation in the body. The investigators hypothesize that tesamorelin will decrease fat accumulation in the liver and muscle and will decrease markers of inflammation, with either neutral or beneficial effects on glucose metabolism.


Eligibility criteria: Inclusion Criteria:

1. Men and women age 18-65
2. Previously diagnosed HIV infection
3. Stable antiviral regimen for at least 12 weeks prior to enrollment
4. WC\>95 cm and WHR\>0.94 for male, WC\>94 cm and WHR\>0.88 for female occurring in the context of treatment for HIV disease
5. Subjective evidence of at least one of the following recent changes, occurring during the treatment of HIV disease: increased abdominal girth, relative loss of fat in the extremities, or relative loss of fat in the face
6. For female subjects 40yo or older, negative mammogram within one year of baseline

Exclusion Criteria:

1. Use of anti-diabetic agents, Megace, testosterone or any steroid use within 6 months of the study. Stable use of testosterone (\> 6 mos) at dose equivalent to 200 mg IM q 2 weeks or \< 10g/day to skin will be permitted.
2. Use of GH or GHRH within the past 6 months
3. Change in lipid lowering or antihypertensive regimen within 3 months of screening
4. Fasting blood sugar \> 126 mg/dL, SGOT \> 2.5 times ULN, HgB \< 12.0 g/dL, creatinine \> 1.4 mg/dL, CD4 count \< 200
5. Severe chronic illness or active malignancy or history of pituitary malignancy or history of colon cancer
6. For men, history of prostate cancer or evidence of prostate malignancy by PSA \> 5 ng/mL
7. Prior history of hypopituitarism, head irradiation or any other condition known to affect the GH axis
8. For women, positive urine hCG
9. Oral contraceptives, depo provera or combined progesterone-estrogen injections, transdermal contraceptive patches, estrogen or progestin coated IUD's within 6 months of the study.
10. Routine MRI exclusion criteria such as the presence of a pacemaker or cerebral aneurysm clip.

Primary outcomes:
measure: Liver Fat
timeFrame: 6 months
measure: Visceral Adipose Tissue
timeFrame: 6 months
Secondary outcomes:
measure: Intramyocellular Lipid
timeFrame: 6 months
measure: Endogenous Growth Hormone Secretion
timeFrame: 6 months
measure: Insulin Sensitivity
timeFrame: 6 months
measure: HbA1c
timeFrame: 6 months
measure: Insulin Like Growth Factor 1 (IGF-I)
timeFrame: 6 months
measure: Lipid Panel
timeFrame: 6 months
measure: Carotid Intimal Medial Thickness (cIMT)
timeFrame: 6 months
measure: Glucose Tolerance
timeFrame: 6 months
measure: Adiponectin
timeFrame: 6 months
measure: Hemostatic Markers
timeFrame: 6 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Steven Grinspoon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, Grinspoon SK. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014 Jul 23-30;312(4):380-9. doi: 10.1001/jama.2014.8334.
citation: Braun LR, Feldpausch MN, Czerwonka N, Torriani M, Grinspoon SK, Stanley TL. Fibroblast growth factor 21 decreases after liver fat reduction via growth hormone augmentation. Growth Horm IGF Res. 2017 Dec;37:1-6. doi: 10.1016/j.ghir.2017.10.002. Epub 2017 Oct 7.