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

Phase 1

Completed

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

Interventions: Drug: Rosiglitazone
Drug: Recombinant human growth hormone + rosiglitazone

Registration Number: NCT00130286

Lead Sponsor: Weill Medical College of Cornell University

Brief Summary: 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: 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:

1. Growth hormone (one injection, daily) PLUS rosiglitazone (one tablet, twice daily).

2. Growth hormone PLUS rosiglitazone placebo ("sugar pill").

3. Growth hormone placebo (plain water injection) PLUS rosiglitazone.

4. 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 77

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
rhGH + rosi	Recombinant human growth hormone + rosiglitazone	Recombinant human growth hormone + rosiglitazone
rhGH placebo + rosi	Recombinant human growth hormone + rosiglitazone	Placebo for recombinant human growth hormone + rosiglitazone
rhGH + rosi placebo	Recombinant human growth hormone + rosiglitazone	Recombinant human growth hormone + placebo for rosiglitazone
Double placebo	Recombinant human growth hormone + rosiglitazone	Placebo for recombinant human growth hormone + placebo for rosiglitazone
Double placebo	Rosiglitazone	Placebo for recombinant human growth hormone + placebo for rosiglitazone
rhGH + rosi	Rosiglitazone	Recombinant human growth hormone + rosiglitazone
rhGH placebo + rosi	Rosiglitazone	Placebo for recombinant human growth hormone + rosiglitazone
rhGH + rosi placebo	Rosiglitazone	Recombinant human growth hormone + placebo for rosiglitazone

Primary Outcome Measures

Name	Time	Method
Change in Insulin Sensitivity	12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change in Visceral Adipose Tissue Volume	12 weeks	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.
Change in Subcutaneous Adipose Tissue Volume	12 weeks	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.

Trial Locations

Locations (4): Cornell HIV Clinical Trials Unit, Weill Medical College of Cornell University
🇺🇸
New York, New York, United States
AIDS Community Research Initiative of America (ACRIA)
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New York, New York, United States
St. Luke's-Roosevelt Hospital Center
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New York, New York, United States
Columbia University College of Physicians and Surgeons
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New York, New York, United States