Clinical trial NCT00006190: A Study to Determine How and Why HIV-Infected Subjects on Anti-viral Treatment Develop Lipodystrophy
Official title: The Study of Mechanisms of Lipodystrophy in HIV-Infected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Lipodystrophy
Keywords: Lipoproteins
Insulin resistance
Adipose tissue
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
First posted: 2000-08-28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: DIAGNOSTIC

Brief summary: HIV infection is a major global health problem. Survival and quality of life for HIV subjects has tremendously improved with the advent of a class of antivirals called protease inhibitors and the utilization of highly active combination therapy. However, such therapy has been associated with a syndrome called lipodystrophy. This lipodystrophy syndrome causes body shape changes; typically thinning and loss of fat from the arms, legs and face, with increased fat appearing in the abdomen and neck. There are also metabolic changes which occur, and subjects can develop increased triglycerides, increased cholesterol and an increased risk for diabetes as indicated by increasing insulin resistance. This study will take HIV positive subjects who have not yet started antiviral medications (treatment naive)and randomly assign them to one of two treatment arms. These treatment arms will be: Sustiva/Zerit/Epivir vs. Viracept/Zerit/Epivir The subjects will be treated and followed for two years and have extensive metabolic testing, skinfold thickness measurements, MRI scans and other measures to determine if and how they are experiencing changes in metabolism or body shape and to discover the mechanism of why this occurs. Understanding the mechanism should allow researchers to design interventions for subjects who have lipodystrophy and strategies to prevent lipodystrophy from occurring to subjects treated with antivirals in the future.


Eligibility criteria: Inclusion Criteria:

* CD4 count \> 200 cells/mm
* HIV RNA (viral load) \<= 100,000 copies/ml
* No previous antiviral therapy

Exclusion Criteria:

* AIDS or opportunistic infections
* Active intravenous drug users
* Use of: corticosteroids, androgens, lipid-lowering drugs, anti-fungal medications, oxandrolone, megace, dehydroepiandrosterone.
* Subjects with diabetes mellitus
* Subjects who consume \> 2 alcoholic drinks per day
* Pregnant women, premenopausal women unless adequate birth control is in use.
* Acute or chronic liver diseases, liver enzymes elevations \> 2.5 times the upper limit of normal.
* Anemia, an Hct \< 35% for men, or \< 32% for women.
* Abnormal thyroid function tests.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Dr. Abhimanyu Garg
role: PRINCIPAL_INVESTIGATOR
affiliation: UT Southwestern Medical Center
name: Dr. Dolores Peterson
affiliation: UT Southwestern Medical Center
name: Dr. Ruth Berggren
References:
citation: Hengel RL, Watts NB, Lennox JL. Benign symmetric lipomatosis associated with protease inhibitors. Lancet. 1997 Nov 29;350(9091):1596. doi: 10.1016/s0140-6736(05)64011-1. No abstract available.
citation: Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, Cooper DA. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998 May 7;12(7):F51-8. doi: 10.1097/00002030-199807000-00003.
citation: Viraben R, Aquilina C. Indinavir-associated lipodystrophy. AIDS. 1998 Apr 16;12(6):F37-9. doi: 10.1097/00002030-199806000-00001.
citation: Shaw AJ, McLean KA, Evans BA. Disorders of fat distribution in HIV infection. Int J STD AIDS. 1998 Oct;9(10):595-9. doi: 10.1258/0956462981921189.
citation: Kotler DP, Rosenbaum K, Wang J, Pierson RN. Studies of body composition and fat distribution in HIV-infected and control subjects. J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Mar 1;20(3):228-37. doi: 10.1097/00042560-199903010-00003.
citation: Lo JC, Mulligan K, Tai VW, Algren H, Schambelan M. "Buffalo hump" in men with HIV-1 infection. Lancet. 1998 Mar 21;351(9106):867-70. doi: 10.1016/S0140-6736(97)11443-X.