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

Condition(s) targeted: HIV-Associated Lipodystrophy Syndrome; Insulin Resistance; HIV Infections; Metabolic Syndrome X; Body Weight Changes

Intervention: Recombinant Human Growth Hormone (Drug); Rosiglitazone (Drug); Recombinant Human Growth Hormone and Rosiglitazone (Drug); Placebo human growth hormone and placebo rosiglitazone (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Official(s) and/or principal investigator(s):
Marshall J Glesby, MD, PhD, Principal Investigator, Affiliation: Weill Medical College of Cornell University

Overall contact:
Kirsis Ham, MSN, FNP, Phone: 212-746-4166, Email: kah2003@med.cornell.edu

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.

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 design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Safety/Efficacy Study

Primary outcome: Change in insulin sensitivity

Secondary outcome:

Change in body fat (total and regional; visceral and subcutaneous)

Other body composition and metabolic endpoints

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).

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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)

Kirsis Ham, MSN, FNP, Phone: 212-746-4166, Email: kah2003@med.cornell.edu

Cornell HIV Clinical Trials Unit, Weill Medical College of Cornell University, New York, New York 10021, United States; Recruiting
Kirsis Ham, MSN, CFNP, Phone: 212-746-4166, Email: kah9003@med.cornell.edu
Valery Hughes, FNP, Phone: 212-746-4393, Email: vah9001@med.cornell.edu
Marshall J Glesby, MD, PhD, Principal Investigator

St. Luke's-Roosevelt Hospital Center, New York, New York 10025, United States; Recruiting
Janet Sheikhan, RN, Phone: 212-523-3671
Ellen Engelson, Ed.D., Phone: 212-523-3670
Donald Kotler, MD, Principal Investigator

Columbia University College of Physicians and Surgeons, New York, New York 10032, United States; Recruiting
Carlos Lopez, MD, Phone: 212-305-2920
Daniel Donovan, MD, MSc, Principal Investigator
Michael Yin, MD, MSc, Sub-Investigator

AIDS Community Research Initiative of America (ACRIA), New York, New York 10018, United States; Recruiting
Yuriy Akulov, MD, Phone: 212-924-3934, Ext: 124, Email: yakulov@acria.org
Liza Kelly-Rossini, NP, Phone: 212-924-3934, Ext: 125, Email: lkelly@acria.org

Starting date: March 2005
Ending date: January 2010
Last updated: October 5, 2009