Effects of Treatment Changes on Fat Wasting in the Arms and Legs of HIV Patients

NCT ID: NCT00028314

Last Updated: 2013-07-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-03-31

Study Completion Date

2005-03-31

Brief Summary

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The goals of this study are to find out if fat wasting and weight loss in the arms and legs of HIV patients taking highly active antiretroviral therapy (HAART) are caused by nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and if wasting can be reversed if the NRTI is stopped and replaced with other anti-HIV drugs.

Detailed Description

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Recent studies suggest body shape changes, fat redistribution, and fat lipoatrophy may be related to the NRTI component of patients' HAART and not to the protease inhibitor (PI) component. The hypothesis of this study is that thymidine analogues such as stavudine (d4T) and zidovudine (ZDV) cause lipoatrophy more so than non-thymidine analogues and that removal of thymidine analogues from HAART in patients with defined lipoatrophy will reverse this process.

In Step 1, patients will undergo axial mid-thigh and abdomen computer tomography (CT) scans. If the CT scans are readable, patients are restrictively and randomly assigned to 1 of 2 treatment arms in Step 2. Patients in Arm A-1 will replace the thymidine analogue component (stavudine \[d4T\] or zidovudine \[ZDV\]) of their HAART with abacavir (ABC). Patients in Arm B-1 will discontinue their current HAART and will receive a PI and a nonnucleoside reverse transcriptase inhibitor (NNRTI), either lopinavir/ritonavir (LPV/r) and nevirapine (NVP) or atazanavir, ritonavir, and NVP. Patients currently on efavirenz (EFV) not provided by the study may choose to continue with EFV instead of switching to NVP. Comparisons will be made to the baseline values of subcutaneous fat measured by mid-thigh and abdominal CT. Patients in Arms A-1 and B-1 remain on study for a total of 48 weeks and do not advance to Step 3.

Two additional groups (Arms A-2 and B-2) made no changes to HAART for 28 weeks to evaluate the natural history of change in lipoatrophy over time; accrual into these groups and into Step 3 has been discontinued. At Week 28, patients in Arms A-2 and B-2 were registered to Step 3 and switched from HAART to a designated new treatment. Arm A-2 patients will replace d4T or ZDV with ABC for 48 weeks. Arm B-2 patients replace their HAART with LPV/r plus NVP for 48 weeks. If patients in Arms A-2 and B-2 have not completed the 28-week delay and have not switched regimens, they will enter Step 4 and be reregistered into Arms A-1 and B-1, respectively, remaining on their treatment assignment for 48 weeks. If patients in Arms A-2 and B-2 have already switched regimens, then they will continue on their new regimens until Week 76.

Conditions

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HIV Infections Lipodystrophy Wasting Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Abacavir sulfate

Intervention Type DRUG

Atazanavir/Ritonavir

Intervention Type DRUG

Lopinavir/Ritonavir

Intervention Type DRUG

Nevirapine

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* HIV infected
* Experiencing a loss of fat since starting anti-HIV therapy, especially in the arms and legs
* Receiving anti-HIV therapy of 3 or more drugs, including either stavudine or zidovudine, for 24 weeks or more prior to study screening
* Viral load less than 500 copies/ml at study screening and within 60 days prior to study entry
* CD4 count of 100 or more cells/mm3 obtained within 60 days prior to study entry
* Approved methods of contraception
* Written informed consent

Exclusion Criteria

* Currently receiving abacavir sulfate or have received abacavir sulfate in the past AND any or all of the following: unable to tolerate lopinavir/ritonavir (LPV/r) or nevirapine (NVP); failed anti-HIV treatment containing LPV/r, any other 2 PIs, or any other NNRTI; taking lamivudine (3TC) or tenofovir disoproxil fumarate (TDF) for hepatitis B virus infection and need to remain on a 3TC- or TDF-containing regimen; or have a low chance of response to LPV/r plus NVP
* Cancer treatment 6 months prior to study entry
* Initiated oral drugs to lower blood sugar level 24 weeks prior to study entry. Patients who have taken oral drugs to lower their blood sugar levels for 24 weeks or more prior to study entry are eligible.
* Began therapy with male sex hormones 24 weeks prior to study entry. Patients who have had continuous, stable therapy with male sex hormones for 24 weeks or more prior to study entry are eligible.
* Certain medications within 14 days prior to study entry
* Serious illness within 14 days prior to study entry
* Hepatitis within 60 days prior to study entry
* Thyroid problems
* Drug or alcohol use which, in the opinion of the investigator, would interfere with the study
* Currently using experimental agents except when approved by the study
* Pregnant or breastfeeding
Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert L Murphy, MD

Role: STUDY_CHAIR

Northwestern University Medical Center

Pablo Tebas, MD

Role: STUDY_CHAIR

University of Pennsylvania, Adult Clinical Trials Unit

Locations

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UCLA CARE Center CRS

Los Angeles, California, United States

Site Status

Harbor-UCLA Med. Ctr. CRS

Torrance, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Site Status

Cook County Hosp. CORE Ctr.

Chicago, Illinois, United States

Site Status

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Site Status

Indiana Univ. School of Medicine, Wishard Memorial

Indianapolis, Indiana, United States

Site Status

Methodist Hosp. of Indiana

Indianapolis, Indiana, United States

Site Status

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, United States

Site Status

SSTAR, Family Healthcare Ctr.

Fall River, Massachusetts, United States

Site Status

University of Minnesota, ACTU

Minneapolis, Minnesota, United States

Site Status

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

Beth Israel Med. Ctr., ACTU

New York, New York, United States

Site Status

NY Univ. HIV/AIDS CRS

New York, New York, United States

Site Status

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Site Status

MetroHealth CRS

Cleveland, Ohio, United States

Site Status

The Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, United States

Site Status

The Miriam Hosp. ACTG CRS

Providence, Rhode Island, United States

Site Status

Rhode Island Hosp.

Providence, Rhode Island, United States

Site Status

Vanderbilt Therapeutics CRS

Nashville, Tennessee, United States

Site Status

Univ. of Texas Medical Branch, ACTU

Galveston, Texas, United States

Site Status

Countries

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United States

References

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Calza L, Manfredi R, Chiodo F. Dyslipidaemia associated with antiretroviral therapy in HIV-infected patients. J Antimicrob Chemother. 2004 Jan;53(1):10-4. doi: 10.1093/jac/dkh013. Epub 2003 Nov 25.

Reference Type BACKGROUND
PMID: 14645323 (View on PubMed)

Calza L, Manfredi R, Chiodo F. Hyperlipidaemia in patients with HIV-1 infection receiving highly active antiretroviral therapy: epidemiology, pathogenesis, clinical course and management. Int J Antimicrob Agents. 2003 Aug;22(2):89-99. doi: 10.1016/s0924-8579(03)00115-8.

Reference Type BACKGROUND
PMID: 12927947 (View on PubMed)

Carr A, Miller J, Law M, Cooper DA. A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS. 2000 Feb 18;14(3):F25-32. doi: 10.1097/00002030-200002180-00001.

Reference Type BACKGROUND
PMID: 10716495 (View on PubMed)

McComsey G. Update on mitochondrial toxicity of antiretrovirals and its link to lipodystrophy. AIDS Rev. 2002 Jul-Sep;4(3):140-7.

Reference Type BACKGROUND
PMID: 12416448 (View on PubMed)

Mallal SA, John M, Moore CB, James IR, McKinnon EJ. Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection. AIDS. 2000 Jul 7;14(10):1309-16. doi: 10.1097/00002030-200007070-00002.

Reference Type BACKGROUND
PMID: 10930144 (View on PubMed)

Tebas P, Zhang J, Hafner R, Tashima K, Shevitz A, Yarasheski K, Berzins B, Owens S, Forand J, Evans S, Murphy R. Peripheral and visceral fat changes following a treatment switch to a non-thymidine analogue or a nucleoside-sparing regimen in HIV-infected subjects with peripheral lipoatrophy: results of ACTG A5110. J Antimicrob Chemother. 2009 May;63(5):998-1005. doi: 10.1093/jac/dkp071. Epub 2009 Mar 19.

Reference Type RESULT
PMID: 19299471 (View on PubMed)

Other Identifiers

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AACTG A5110

Identifier Type: -

Identifier Source: secondary_id

ACTG A5110

Identifier Type: -

Identifier Source: secondary_id

A5110

Identifier Type: -

Identifier Source: org_study_id

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