Clinical trial NCT00130286: Growth Hormone and/or Rosiglitazone for HIV-Associated Increased Abdominal Fat and Insulin Resistance
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV-Associated Lipodystrophy Syndrome
Insulin Resistance
HIV Infections
Metabolic Syndrome X
Body Weight Changes
Keywords: Lipodystrophy
HIV
Growth hormone
Rosiglitazone
Visceral fat
Metabolic syndrome
Treatment Experienced
Visceral fat accumulation
fat accumulation
HIV-Associated Metabolic Syndrome
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2005-08-15
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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)

Primary outcomes:
measure: Change in Insulin Sensitivity
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in Visceral Adipose Tissue Volume
timeFrame: 12 weeks
measure: Change in Subcutaneous Adipose Tissue Volume
timeFrame: 12 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: AIDS Community Research Initiative of America (ACRIA)
state: New York
city: New York
country: United States
facility: Cornell HIV Clinical Trials Unit, Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: St. Luke's-Roosevelt Hospital Center
state: New York
city: New York
country: United States
facility: Columbia University College of Physicians and Surgeons
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Marshall J Glesby, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Glesby MJ, Albu J, Chiu YL, Ham K, Engelson E, He Q, Muthukrishnan V, Ginsberg HN, Donovan D, Ernst J, Lesser M, Kotler DP. Recombinant human growth hormone and rosiglitazone for abdominal fat accumulation in HIV-infected patients with insulin resistance: a randomized, double-blind, placebo-controlled, factorial trial. PLoS One. 2013 Apr 12;8(4):e61160. doi: 10.1371/journal.pone.0061160. Print 2013.
citation: Kotler DP, He Q, Engelson ES, Albu JB, Glesby MJ. The effect of recombinant human growth hormone with or without rosiglitazone on hepatic fat content in HIV-1-infected individuals: a randomized clinical trial. Antivir Ther. 2016;21(2):107-16. doi: 10.3851/IMP2927. Epub 2014 Dec 23.