Physiologic Growth Hormone Effects in HIV Lipodystrophy

Study Overview
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Brief Summary
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This study will investigate long-term, low-dose growth hormone administration in HIV-infected patients with reduced growth hormone (GH) secretion and increased visceral adiposity. We hypothesize that low-dose growth hormone will reduce visceral fat. Secondary endpoints will include measures of insulin-like growth factor-1 (IGF-1), glucose homeostasis, lipids, blood pressure,bone density, cardiovascular risk and safety parameters.

Detailed Description
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This study will investigate long-term, low-dose growth hormone administration in HIV-infected patients with reduced growth hormone (GH) secretion and increased visceral adiposity. We hypothesize that low-dose growth hormone will reduce visceral fat preferentially over subcutaneous fat, and increase lean body mass. Secondary endpoints will include measures of IGF-1, glucose homeostasis, lipids, blood pressure,bone density, cardiovascular risk and safety parameters. Dosing of growth hormone will be based on patients' IGF-1 levels and will not exceed 6mcg/kg/day.

Official Title
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Physiologic Growth Hormone Effects in HIV Lipodystrophy

Conditions
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HIV Infections, AIDS

Intervention / Treatment
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* Drug: recombinant human growth hormone
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women age 18-60 Previously diagnosed HIV infection Stable antiviral regimen for at least 12 weeks prior to enrollment Waist-to-hip ratio >0.90 for men and >0.85 for women Evidence of at least one of the following recent changes: *increased abdominal girth, *relative loss of fat in the extremities, *relative loss of fat in the face Simulated peak GH response to arginine/GHRH of less than 7.5 mcg/dL Exclusion Criteria: Use of Megace, anti-diabetic agents, GH, or other anabolic agents, pharmacologic glucocorticoid (prednisone >5 mg/day or its equivalent) for 3 months prior to enrollment. Patients on a standard dose of testosterone for documented hypogonadism will be allowed to enter the protocol. Women taking standard estrogen replacement therapy for >3 months will be allowed in the study. Diabetes mellitus Other severe chronic illness HgB <9.0 g/dL, creatinine >1.4 mg/dL, or PSA >4 ng/mL Positive BHCG or failure to use appropriate birth control during study. Acceptable methods include oral contraceptives, depo provera or combined progesterone-estrogen injections, transdermal contraceptive patches, IUD's, barrier devices (condoms, diaphragms), and abstinence. Carpal tunnel syndrome Active malignancy or history of pituitary malignancy, history of colon cancer or prostate malignancy

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>recombinant human growth hormone subcutaneously once a day | Drug: recombinant human growth hormone<br>* growth hormone dosed by weight and IGF-1 level,subcutaneously once a day, 18 months<br>* Other names: Serostim;|
| Placebo Comparator: 2<br>placebo subcutaneously once a day | Drug: placebo<br>* placebo subcutaneously once a day, 18 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Visceral Adipose Tissue Area From Baseline to 18 Months | change in visceral adipose tissue area as measured by single-slice abdominal computed tomographic scan | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insulin-like Growth Factor-I From Baseline to 18 Months | Change in insulin-like growth factor-1 | 18 months | 
| Change in Trunk Fat |  | 18 months | 
| Change in Fasting Glucose | change in fasting glucose | 18 months | 
| Change in Trunk to Extremity Ratio | change in trunk to extremity ratio | 18 months | 
| Change in Triglycerides | Change in triglycerides | 18 months | 
| Change in Subcutaneous Adipose Tissue | Change in subcutaneous adipose tissue | 18 months | 
| Change in CD4 Cells | Change in CD4 cells | 18 months | 
| Change in Logarithm HIV Viral Load | Change in logarithm base 10 HIV viral load | 18 months | 
| Change in Lean Body Mass | change in lean body mass | 18 months | 
| Change in Quality of Life Score From the Medical Outcomes Study-HIV Survey From Baseline to 18 Months | Change in quality of life score was measured by the Medical Outcomes Study-HIV (MOS-HIV)survey. The MOS-HIV asks patients to report on health-related quality of life and physical function from the past 4 days. The scoring range is 0-100, and a higher score indicates better quality of life. | 18 months | 
| Change in Diastolic Blood Pressure | Change in diastolic blood pressure | 18 months | 
| Change in Adiponectin | Change in adiponectin | 18 months | 
| Change in Carotid Intima Media Thickness (IMT) | change in carotid intima media thickness (IMT) | 18 months | 
| Change in Body Mass Index | Change in body mass index | 18 months | 
| Change in Extremity Fat | Change in extremity fat | 18 months | 
| Change in 2-hour Glucose | Change in 2-hour glucose | 18 months | 
| Change in Systolic Blood Pressure | Change in systolic blood pressure | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, IGF-I, lipodystrophy, growth hormone, visceral fat, Treatment Experienced