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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 77
- Locations
- 4
- Primary Endpoint
- Change in Insulin Sensitivity
Study Overview
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:
- 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
Arms & Interventions
rhGH + rosi
Recombinant human growth hormone + rosiglitazone
Intervention: Rosiglitazone (Drug)
rhGH + rosi
Recombinant human growth hormone + rosiglitazone
Intervention: Recombinant human growth hormone + rosiglitazone (Drug)
rhGH placebo + rosi
Placebo for recombinant human growth hormone + rosiglitazone
Intervention: Rosiglitazone (Drug)
rhGH placebo + rosi
Placebo for recombinant human growth hormone + rosiglitazone
Intervention: Recombinant human growth hormone + rosiglitazone (Drug)
rhGH + rosi placebo
Recombinant human growth hormone + placebo for rosiglitazone
Intervention: Rosiglitazone (Drug)
rhGH + rosi placebo
Recombinant human growth hormone + placebo for rosiglitazone
Intervention: Recombinant human growth hormone + rosiglitazone (Drug)
Double placebo
Placebo for recombinant human growth hormone + placebo for rosiglitazone
Intervention: Rosiglitazone (Drug)
Double placebo
Placebo for recombinant human growth hormone + placebo for rosiglitazone
Intervention: Recombinant human growth hormone + rosiglitazone (Drug)
Outcomes
Primary Outcomes
Change in Insulin Sensitivity
Time Frame: 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 Outcomes
- Change in Visceral Adipose Tissue Volume(12 weeks)
- Change in Subcutaneous Adipose Tissue Volume(12 weeks)
Investigators
Marshall Jay Glesby, MD, PhD
Professor of Medicine and Public Health
Weill Medical College of Cornell University