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

Study Overview
=================
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.

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

Conditions
-----------------
HIV Lipodystrophy

Intervention / Treatment
-----------------
* Drug: Growth hormone
* Drug: Growth Hormone Releasing Hormone


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GH 6mcg/kg/d<br>Recombinant human growth hormone 6mcg/kg SC once daily | Drug: Growth hormone<br>* Recombinant Human Growth Hormone (Teva pharmaceuticals), with one arm receiving 6mcg/kg SC once daily for two weeks and the other arm receiving 2mg SC once daily for two weeks<br>* Other names: rhGH from Teva Pharmaceuticals;|
| Experimental: GH 2mg daily<br>Recombinant human growth hormone 2mg SC once daily | Drug: Growth hormone<br>* Recombinant Human Growth Hormone (Teva pharmaceuticals), with one arm receiving 6mcg/kg SC once daily for two weeks and the other arm receiving 2mg SC once daily for two weeks<br>* Other names: rhGH from Teva Pharmaceuticals;|
| Experimental: Growth Hormone Releasing Hormone<br>Growth Hormone Releasing Hormone (Tesamorelin) 2mg daily, injected subcutaneously, x 2 weeks | Drug: Growth Hormone Releasing Hormone<br>* Tesamorelin (GHRH) 2mg SC QD x 2 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overnight Mean Growth Hormone Secretion After 2 Weeks of Study Drug | 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. | after 2 weeks treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity | 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 | after two weeks treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV lipodystrophy, growth hormone, growth hormone releasing hormone