Effects of Short-term Growth Hormone in HIV-infected Patients

Not Applicable

Completed

Brief Summary: The purpose of this study is to examine the short-term effects of two different doses of growth hormone, compared to treatment with growth hormone releasing hormone, on the brain's secretion of growth hormone and the body's glucose metabolism. We hypothesize that growth hormone administration will alter the body's endogenous pulsatile growth hormone secretion and that higher dose growth hormone may decrease insulin sensitivity. We hypothesize that growth hormone releasing hormone will augment endogenous GH pulsatility and be neutral to insulin sensitivity.

Detailed Description: The primary objective of this study is to determine the differential effects of growth hormone releasing hormone (GHRH) vs. low dose physiologic growth hormone (GH) vs. higher dose GH treatment and withdrawal on endogenous overnight growth hormone secretion and pulsatility, as well as insulin-stimulated glucose uptake. Subjects with HIV-infection will be randomized to receive one of three treatments: GHRH 2mg/day, or growth hormone 6mcg/kg/day (physiologic "low" dose), or growth hormone 2mg/day ("higher" dose) for 2 weeks. At baseline and after two weeks of treatment, we will assess overnight growth hormone by frequent sampling as well as insulin stimulated glucose uptake by clamp. Subjects will then stop the treatment and will return for an identical assessment after a 2 week withdrawal period.

Recruitment & Eligibility

Inclusion Criteria

previously diagnosed HIV infection
Stable antiretroviral regimen for at least 12 weeks prior to enrollment
Waist circumference >/= 95cm and waist-to-hip ratio >/= 0.94 for males or waist circumference >/=94cm and WHR >/= 0.88 for females, occurring in the context of treatment for HIV disease
Subjective evidence of at least one of the following 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

Exclusion Criteria

Use of anti-diabetic agents, Megace, testosterone, or any steroid use within 6 months of the study
Use of GH or Growth hormone releasing factor within six months of starting the study
Change in lipid lowering or antihypertensive regimen within 3 months of screening
Fasting blood sugar >126mg/dL, SGOT > 2.5 times ULN, Hgb < 12.0 g/dL, creatinine > 1.4 mg/dL, FSH > 20 IU/L in women, or CD4 count < 200
Carpal tunnel syndrome
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 > 5ng/mL
Prior history of hypopituitarism, head irradiation, or any other condition known to affect the GH axis
positive beta-HCG (women only)
Oral contraceptives, depo provera, or combined progesterone-estrogen injections, transdermal contraceptive patches, estrogen or progestin coated IUD's within 6 months of the study
weight < 110 pounds

Arm && Interventions

Group	Intervention	Description
Growth Hormone Releasing Hormone	Growth Hormone Releasing Hormone	Growth Hormone Releasing Hormone (Tesamorelin) 2mg daily, injected subcutaneously, x 2 weeks
GH 2mg daily	Growth hormone	Recombinant human growth hormone 2mg SC once daily
GH 6mcg/kg/d	Growth hormone	Recombinant human growth hormone 6mcg/kg SC once daily

Primary Outcome Measures

Name	Time	Method
Overnight Mean Growth Hormone Secretion After 2 Weeks of Study Drug	after 2 weeks treatment	Serum was sampled for growth hormone concentrations every 20 minutes between 20:00 (8pm) and 07:40 (7:40am). Subjects in GH 6mcg/kg/day and GH 2mg daily groups received their final dose of study drug approximately 36 hours prior to start of sampling. Subjects in Growth Hormone Releasing Hormone group received their final dose of study drug approximately 8 hours prior to start of sampling.

Secondary Outcome Measures

Name	Time	Method
Insulin Sensitivity	after two weeks treatment	insulin-stimulated glucose uptake as measured by euglycemic hyperinsulinemic clamp; "M" value (infusion rate with space correction, using method of DeFronzo) for the steady state between 100-120 minutes of clamp is given