Effects of Growth Hormone Releasing Hormone in HIV

Not Applicable

Completed

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.

Recruitment & Eligibility

Inclusion Criteria

Men and women age 18-65
Previously diagnosed HIV infection
Stable antiviral regimen for at least 12 weeks prior to enrollment
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
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
For female subjects 40yo or older, negative mammogram within one year of baseline

Exclusion Criteria

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.
Use of GH or GHRH within the past 6 months
Change in lipid lowering or antihypertensive regimen within 3 months of screening
Fasting blood sugar > 126 mg/dL, SGOT > 2.5 times ULN, HgB < 12.0 g/dL, creatinine > 1.4 mg/dL, CD4 count < 200
Severe chronic illness or active malignancy or history of pituitary malignancy or history of colon cancer
For men, history of prostate cancer or evidence of prostate malignancy by PSA > 5 ng/mL
Prior history of hypopituitarism, head irradiation or any other condition known to affect the GH axis
For women, positive urine hCG
Oral contraceptives, depo provera or combined progesterone-estrogen injections, transdermal contraceptive patches, estrogen or progestin coated IUD's within 6 months of the study.
Routine MRI exclusion criteria such as the presence of a pacemaker or cerebral aneurysm clip.

Arm && Interventions

Group	Intervention	Description
Placebo (inactive injection)	placebo	Placebo 2mg daily given subcutaneously for the first 6 months of the study, followed by 6 months of tesamorelin (growth hormone releasing hormone) 2mg daily during an open label phase
Tesamorelin	tesamorelin	Tesamorelin (growth hormone releasing hormone) 2mg daily given subcutaneously x 6 months during randomized phase, followed by 6 months of open-label tesamorelin at same dose

Primary Outcome Measures

Name	Time	Method
Liver Fat	6 months	Hepatic fat as measured by magnetic resonance (MR) spectroscopy, and expressed by normalizing lipid to water and expressing as a percent (lipid-to-water percent).
Visceral Adipose Tissue	6 months	Change in visceral adipose tissue area as measured by single-slice computed tomography (CT) scan at the L4 vertebra.

Secondary Outcome Measures

Name	Time	Method
Intramyocellular Lipid	6 months	Intramyocellular lipid (IMCL) as measured by magnetic resonance (MR) spectroscopy of the calf. Soleus IMCL normalized to creatinine (IMCL/Cr based on areas determined by spectroscopy) was measured. The change over 6 months is reported.
Endogenous Growth Hormone Secretion	6 months	Endogenous growth hormone (GH) concentrations measured by overnight frequent blood sampling every 20 minutes. Mean overnight GH concentration is given.
Insulin Sensitivity	6 months	In a subgroup of 1/2 of the subjects, euglycemic hyperinsulinemic clamp will be performed to assess insulin-stimulated glucose uptake. Insulin stimulated glucose uptake (M) calculated using the method of DeFronzo is shown.
HbA1c	6 months	Hemoglobin A1c.
Insulin Like Growth Factor 1 (IGF-I)	6 months	Insulin Like Growth Factor 1 (IGF-I).
Lipid Panel	6 months	Fasting lipids. Triglyceride value is given.
Carotid Intimal Medial Thickness (cIMT)	6 months	Carotid Intimal Medial Thickness (cIMT).
Glucose Tolerance	6 months	Glucose tolerance as measured by standard oral glucose tolerance test. 2-hour glucose is given.
Adiponectin	6 months	adiponectin.
Hemostatic Markers	6 months	Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) measured in serum.