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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00130286
• Other study ID #: 65515
• Secondary ID: R01DK065515
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 12, 2005
• Last updated: February 10, 2014
• Start date: March 2005
• Est. completion date: August 2010

Study information

• Verified date: February 2014
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Rosiglitazone
4 mg tablet twice a day x 12 weeks (double-blind phase)
• Recombinant human growth hormone + rosiglitazone
Recombinant human growth hormone or placebo 3 mg s.c. x 12 weeks (double-blind phase)

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No