Growth Hormone and/or Rosiglitazone for HIV-Associated Increased Abdominal Fat and Insulin Resistance

Study Overview
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Brief Summary
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The purpose of the study is to determine if the combination of recombinant human growth hormone plus rosiglitazone (an insulin-sensitizing drug) is safe and more effective than either drug alone (or no active therapy) for the treatment of fat accumulation in people with HIV infection and insulin resistance.

Detailed Description
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A number of people with HIV infection who gain weight in the abdomen (sometimes called lipodystrophy) also have a high level of the sugar-controlling hormone called insulin. These people need to produce this extra insulin to help keep their blood sugar normal. This is called insulin resistance. Studies have shown that growth hormone (also called Serostim) can decrease abdominal fat, but it can also worsen the insulin resistance. Rosiglitazone (also called Avandia) is used to treat insulin resistance in people who have diabetes, so we want to see if taking growth hormone and rosiglitazone together will be better for treating the fat accumulation part of lipodystrophy than either drug alone or no active therapy. The study is 24 weeks long, divided into two 12-week parts. The first part of the study is double-blind, meaning that neither participants nor the study staff will know which drugs participants are on. Participants will be assigned randomly (like flipping a coin) to one of four groups: Growth hormone (one injection, daily) PLUS rosiglitazone (one tablet, twice daily). Growth hormone PLUS rosiglitazone placebo (sugar pill). Growth hormone placebo (plain water injection) PLUS rosiglitazone. Growth hormone placebo PLUS rosiglitazone placebo. Everyone in the study will need to be hospitalized overnight for special tests at the beginning of the study and at week 12. The second part of the study is open-label, meaning that participants and the study staff will know which drugs participants are receiving. All volunteers will receive both active drugs: Growth hormone (one 2 mg injection, every other day) PLUS rosiglitazone (one 4 mg tablet, twice daily).

Official Title
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Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Recombinant Human Growth Hormone and/or Rosiglitazone in the Treatment of Human Immunodeficiency Virus-Associated Visceral Adiposity and Insulin Resistance

Conditions
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HIV-Associated Lipodystrophy Syndrome, Insulin Resistance, HIV Infections, Metabolic Syndrome X, Body Weight Changes

Intervention / Treatment
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* Drug: Rosiglitazone
* Drug: Recombinant human growth hormone + rosiglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-infected On stable Food and Drug Administration (FDA)-approved antiretrovirals for at least 8 weeks Excess abdominal fat based on waist and hip measurements done at the screening visit. [waist greater than 34.7 inches (men) or 29.6 inches (women) and waist to hip ratio greater than 0.95 (men) or 0.9 (women)] Evidence of insulin resistance (based on fasting glucose and insulin levels done at screening) Triglycerides less than 750 mg/dL Exclusion Criteria: Pregnancy Active AIDS-defining infection or other acute illness, within 30 days of entry. Active cancer (except for localized Kaposi's sarcoma) or active brain tumor Any diagnosis of pancreatitis, carpal tunnel syndrome, diabetes, angina, coronary artery disease, or disorder associated with fluid retention (examples: cirrhosis, congestive heart failure) Untreated or uncontrolled high blood pressure, within 30 days of entry. Within 12 weeks of study entry, use of the following: Obesity (fat-reducing) drugs. Anti-diabetic or insulin-sensitizing drugs (examples: rosiglitazone, pioglitazone, or metformin). Systemic glucocorticoids (example: prednisone). Growth hormone or any medication for AIDS-associated wasting. Systemic chemotherapy, interferon, or radiation therapy. Androgenic agents [examples: nandrolone, oxandrolone (Oxandrin) (testosterone replacement therapy is permitted if started more than 30 days before entry)] Appetite stimulants (Marinol, Megace, Periactin). Use of cholesterol lowering drugs, unless started more than 12 weeks before entry Inability to have a magnetic resonance imaging (MRI) scan performed (examples: cardiac pacemaker, intracranial aneurysm clips)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rhGH + rosi<br>Recombinant human growth hormone + rosiglitazone | Drug: Rosiglitazone<br>* 4 mg tablet twice a day x 12 weeks (double-blind phase)<br>Drug: Recombinant human growth hormone + rosiglitazone<br>* Recombinant human growth hormone or placebo 3 mg s.c. x 12 weeks (double-blind phase)<br>|
| Experimental: rhGH placebo + rosi<br>Placebo for recombinant human growth hormone + rosiglitazone | Drug: Rosiglitazone<br>* 4 mg tablet twice a day x 12 weeks (double-blind phase)<br>Drug: Recombinant human growth hormone + rosiglitazone<br>* Recombinant human growth hormone or placebo 3 mg s.c. x 12 weeks (double-blind phase)<br>|
| Experimental: rhGH + rosi placebo<br>Recombinant human growth hormone + placebo for rosiglitazone | Drug: Rosiglitazone<br>* 4 mg tablet twice a day x 12 weeks (double-blind phase)<br>Drug: Recombinant human growth hormone + rosiglitazone<br>* Recombinant human growth hormone or placebo 3 mg s.c. x 12 weeks (double-blind phase)<br>|
| Placebo Comparator: Double placebo<br>Placebo for recombinant human growth hormone + placebo for rosiglitazone | Drug: Rosiglitazone<br>* 4 mg tablet twice a day x 12 weeks (double-blind phase)<br>Drug: Recombinant human growth hormone + rosiglitazone<br>* Recombinant human growth hormone or placebo 3 mg s.c. x 12 weeks (double-blind phase)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insulin Sensitivity | Change in insulin sensitivity value from baseline to week 12 by frequently sampled intravenous glucose tolerance test This assessment was only conducted at baseline and week 12; therefore the change reflects the difference between these two time points. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Visceral Adipose Tissue Volume | Change in visceral adipose tissue volume from baseline to week 12 measured by whole body MRI Data are presented only for subjects who had MRI scans done at both time points. | 12 weeks | 
| Change in Subcutaneous Adipose Tissue Volume | Change in subcutaneous adipose tissue volume from baseline to week 12 by whole body MRI Data are presented only for subjects who had MRI scans done at both time points. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lipodystrophy, HIV, Growth hormone, Rosiglitazone, Visceral fat, Metabolic syndrome, Treatment Experienced, Visceral fat accumulation, fat accumulation, HIV-Associated Metabolic Syndrome