HIV InfectionsNCT00028314
Effects of Treatment Changes on Fat Wasting in the Arms and Legs of HIV Patients
A study testing Abacavir sulfate, Atazanavir/Ritonavir and Lopinavir/Ritonavir in people with HIV Infections and Lipodystrophy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 25 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- HIV Infections, Lipodystrophy, Wasting Disease
- What is being tested?
- Abacavir sulfate, Atazanavir/Ritonavir and Lopinavir/Ritonavir
- How many people
- 150 participants
- Where
- 25 sitesUnited States
- Study dates
- Mar 2002to Mar 2005
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
University of Colorado Hospital CRS
Aurora, Colorado, 80262
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, 02215
Northwestern University CRS
Chicago, Illinois, 60611
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, 60612
Cook County Hosp. CORE Ctr.
Chicago, Illinois
Univ. of Cincinnati CRS
Cincinnati, Ohio, 45267-0405
MetroHealth CRS
Cleveland, Ohio, 44109-1998
The Ohio State University Medical Center
Columbus, Ohio, 432101228
SSTAR, Family Healthcare Ctr.
Fall River, Massachusetts
Univ. of Texas Medical Branch, ACTU
Galveston, Texas, 775550435
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, 96816
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana
Indiana Univ. School of Medicine, Wishard Memorial
Indianapolis, Indiana
Methodist Hosp. of Indiana
Indianapolis, Indiana
UCLA CARE Center CRS
Los Angeles, California, 90095
University of Minnesota, ACTU
Minneapolis, Minnesota, 55455-0392
Vanderbilt Therapeutics CRS
Nashville, Tennessee, 37203
Beth Israel Med. Ctr., ACTU
New York, New York, 10003
NY Univ. HIV/AIDS CRS
New York, New York, 10016
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, 19104
The Miriam Hosp. ACTG CRS
Providence, Rhode Island, 02906
Rhode Island Hosp.
Providence, Rhode Island
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, 63108
Washington U CRS
St Louis, Missouri, 63108
Harbor-UCLA Med. Ctr. CRS
Torrance, California, 90502-2052
About this study
Official title: A Restrictively Randomized, Open-Label, Controlled, Pilot Study of the Effect of a Thymidine Analogue Substitution or Change to a Nucleoside-Sparing Regimen on Peripheral Fat Wasting
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.
Read the detailed description
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
- HIV Infections, Lipodystrophy, Wasting Disease
- Being tested
- Abacavir sulfate, Atazanavir/Ritonavir, Lopinavir/Ritonavir, Nevirapine
- Keywords
- HIV-1, Abacavir, Nevirapine, Ritonavir, RNA, Viral, HIV Protease Inhibitors, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Viral Load, HIV Wasting Syndrome, ABT 378, Treatment Experienced
- Medical subject headings
- HIV Infections, Lipodystrophy, Wasting Syndrome, HIV Wasting Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abacavir sulfateDrug
Atazanavir/RitonavirDrug
Lopinavir/RitonavirDrug
NevirapineDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2001 (estimated)
- Study startMar 2002
- Study completionMar 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 150 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert L Murphy, MD, Study chair, Northwestern University Medical CenterPablo Tebas, MD, Study chair, University of Pennsylvania, Adult Clinical Trials Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00028314
- Sponsor's protocol ID
- A5110
- Other IDs
- AACTG A5110, ACTG A5110
- Status last verified
- Jul 2013
- First submitted
- 20 Dec 2001
- Last updated
- 29 Jul 2013
- Results posted
- No
Publications
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.
PubMed 14645323Calza 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.
PubMed 12927947Carr 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.
PubMed 10716495McComsey G. Update on mitochondrial toxicity of antiretrovirals and its link to lipodystrophy. AIDS Rev. 2002 Jul-Sep;4(3):140-7.
PubMed 12416448Mallal 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.
PubMed 10930144Tebas 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.
PubMed 19299471
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Restrictively Randomized, Open-Label, Controlled, Pilot Study of the Effect of a Thymidine Analogue Substitution or Change to a Nucleoside-Sparing Regimen on Peripheral Fat Wasting
- ClinicalTrials.gov ID
- NCT00028314
- Acronym / sponsor ID
- A5110
- Conditions
- HIV Infections, Lipodystrophy, Wasting Disease
- Keywords
- HIV-1, Abacavir, Nevirapine, Ritonavir, RNA, Viral, HIV Protease Inhibitors, Reverse Transcriptase Inhibitors, Anti-HIV Agents
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Mar 2002
- Study completion
- Mar 2005 (actual)
- First posted
- 21 Dec 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Abacavir sulfate | Drug | – |
| Atazanavir/Ritonavir | Drug | – |
| Lopinavir/Ritonavir | Drug | – |
| Nevirapine | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2013.
- Background: PubMed 14645323Calza 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.
- Background: PubMed 12927947Calza 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.
- Background: PubMed 10716495Carr 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.
- Background: PubMed 12416448McComsey G. Update on mitochondrial toxicity of antiretrovirals and its link to lipodystrophy. AIDS Rev. 2002 Jul-Sep;4(3):140-7.
- Background: PubMed 10930144Mallal 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.
- Results publication: PubMed 19299471Tebas 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert L Murphy, MD study chair
Northwestern University Medical Center
Pablo Tebas, MD study chair
University of Pennsylvania, Adult Clinical Trials Unit
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Abacavir sulfate, Atazanavir/Ritonavir and Lopinavir/Ritonavir in people with HIV Infections and Lipodystrophy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 25 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00028314, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2013.