HIV InfectionsPhase 2NCT00656175
Raltegravir Therapy for Women With HIV and Fat Accumulation
A Phase 2 study testing raltegravir in people with HIV Infections and Lipodystrophy, run by University of California, Los Angeles at 5 sites in 2 countries.
Trial summary
Ritonavir-boosted protease inhibitor (PI) regimens have become a backbone for treatment of people with HIV. However, adverse drug effects, particularly lipodystrophy/lipoatrophy are closely associated with these regimens. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- HIV Infections, Lipodystrophy
- What is being tested?
- raltegravir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Sep 2008to Dec 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry or plasma HIV-1 RNA > 2000 on two occasions,
- Female subjects 18 years or older
- Documented central fat accumulation (defined by waist circumference of > 94 cm or a waist to hip ratio of > 0.88).
- Documented HIV RNA <50 copies/mL at screening and <400 copies/mL in the past 6 months.
- Current antiretroviral therapy with two nucleoside analogues and either a non-nucleoside analogue (nevirapine, efavirenz or TMC125) or an approved protease inhibitor. Patients on NNRTI+PI at study entry will be excluded. Study participants do not need to be on their first regimen. No changes in ART in the 12 weeks prior to screening. The nucleoside backbone must include either tenofovir or abacavir and either lamivudine or emtricitabine. Fixed dose combinations with emtricitabine or abacavir are allowed.
- For females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy, or bilateral oophorectomy and/or tubal ligation), will need a negative serum or urine pregnancy test within 48 hours prior to entry.
- Ability and willingness of subject to provide informed consent.
Who cannot join
- Pregnancy: current or within the past 6 months or breast feeding
- Prior treatment history that would preclude the use of emtricitabine or abacavir as the nucleoside backbone during study treatment
- Current use of metformin or thiazolidinediones.
- Use of growth hormone or growth hormone releasing factor in the last 6 months before screening.
- Change or initiation of anti-hyperlipemic regimen within 3 months prior to randomization; Use of stable anti-hyperlipemic regimen during the study is allowed.
- Current use of androgen therapy.
Show all 13Show fewer
- Intent to modify diet, exercise habits or to enroll in a weight loss intervention during the study period.
- Current or projected need to use rifampin, dilantin or phenobarbital during the 48-week study period.
- Laboratory values at screening of
- ANC >500 cells/mm3
- Hemoglobin <10 gm/dl
- CrCl > 60 ml/min (estimated by Cockcroft-Gault equation)
- AST or ALT > 3 x ULN
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Tufts University School of Medicine
Boston, Massachusetts, 02111
Case School of Medicine
Cleveland, Ohio, 44106
UCLA CARE Center
Los Angeles, California, 90035
Vanderbilt University
Nashville, Tennessee, 37203
About this study
Official title: Phase II Study of Raltegravir as Replacement for Protease Inhibitor or Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Based Antiretroviral Therapy in Women With Fat Accumulation
Ritonavir-boosted protease inhibitor (PI) regimens have become a backbone for treatment of people with HIV. However, adverse drug effects, particularly lipodystrophy/lipoatrophy are closely associated with these regimens. Therefore, there is a need for a drug with comparable effectiveness to the ritonavir boosted PIs without the side effects of dyslipidemia, which has been associated with elevated cholesterol and cardiovascular disease
Raltegravir is an HIV integrase inhibitor in phase III clinical development. To date there are no approved drugs that target the same stage of the HIV-1 lifecycle. However, data from studies indicate that raltegravir is generally safe and well tolerated and has strong antiretroviral activity when used in combination with licensed antiretroviral medications.
Read more
This study aims to demonstrate that patients substituting raltegravir for a PI or NNRTI based antiretroviral regimen will be associated with a 10% reduction in body fat over 24 weeks.
The study will consist of a total of 10 subject visits over a period of 48 weeks. Approximately 40 female patients will participate in this study (approximately 10 at UCLA).
- Conditions
- HIV Infections, Lipodystrophy
- Being tested
- raltegravir
- Keywords
- lipodystrophy, fat, visceral fat, HIV, women, raltegravir, ART, anti HIV therapy, NNRTI, Protease inhibitor, integrase inhibitor, treatment experienced
- Medical subject headings
- HIV Infections, Lipodystrophy, Platelet Glycoprotein IV Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
raltegravirDrug
Also called Isentress
raltegravir
| Study group | Role | What they receive |
|---|---|---|
| Immediate | Active comparator | Immediate switch of PI or NNRTI to Raltegravir Receives: Drug: raltegravir |
| Delayed | Active comparator | Continue current therapy unchanged for 24 weeks, then switch PI or NNRTI to Raltegravir Receives: Drug: raltegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline to 24-week Change in Visceral Adipose Tissue Volume (cm^2)
Adipose tissue volumes were measured via single slice L4-L5 CT scan, and volumes were calculated using cm^2, not cm^3, as is standard protocol at the Tufts University Body Composition Reading Center. The authors acknowledge that cm^2 uses area as a surrogate for volume, but this protocol is well-accepted in our field.
Measured: Baseline and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2008 (estimated)
- Study startSep 2008
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)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 University of California, Los AngelesThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Case Western Reserve University, Vanderbilt University, Tufts University, University Health Network, Toronto
- Responsible party
- Principal investigator, Judith S. Currier, University of California, Los Angeles
- Investigators
- Judith S. Currier, M.D., Principal investigator, University of California, Los AngelesGrace McComsey, M.D., Study chair, Case School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00656175
- Sponsor's protocol ID
- IISP-Raltegravir
- Status last verified
- Dec 2012
- First submitted
- 2 Apr 2008
- Last updated
- 19 Dec 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Lake JE, McComsey GA, Hulgan TM, Wanke CA, Mangili A, Walmsley SL, Boger MS, Turner RR, McCreath HE, Currier JS. A randomized trial of Raltegravir replacement for protease inhibitor or non-nucleoside reverse transcriptase inhibitor in HIV-infected women with lipohypertrophy. AIDS Patient Care STDS. 2012 Sep;26(9):532-40. doi: 10.1089/apc.2012.0135. Epub 2012 Jul 23.
PubMed 22823027Offor O, Utay N, Reynoso D, Somasunderam A, Currier J, Lake J. Adiponectin and the steatosis marker Chi3L1 decrease following switch to raltegravir compared to continued PI/NNRTI-based antiretroviral therapy. PLoS One. 2018 May 10;13(5):e0196395. doi: 10.1371/journal.pone.0196395. eCollection 2018.
PubMed 29746485
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Raltegravir as Replacement for Protease Inhibitor or Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Based Antiretroviral Therapy in Women With Fat Accumulation
- ClinicalTrials.gov ID
- NCT00656175
- Acronym / sponsor ID
- IISP-Raltegravir
- Conditions
- HIV Infections, Lipodystrophy
- Keywords
- lipodystrophy, fat, visceral fat, HIV, women, raltegravir, ART, anti HIV therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Case Western Reserve University, Vanderbilt University, Tufts University, University Health Network, Toronto
- Study start
- Sep 2008
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 10 Apr 2008 (estimated)
- Results
- Posted 19 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ritonavir-boosted protease inhibitor (PI) regimens have become a backbone for treatment of people with HIV. However, adverse drug effects, particularly lipodystrophy/lipoatrophy are closely associated with these regimens. Therefore, there is a need for a drug with comparable effectiveness to the ritonavir boosted PIs without the side effects of dyslipidemia, which has been associated with elevated cholesterol and cardiovascular disease
Raltegravir is an HIV integrase inhibitor in phase III clinical development. To date there are no approved drugs that target the same stage of the HIV-1 lifecycle. However, data from studies indicate that raltegravir is generally safe and well tolerated and has strong antiretroviral activity when used in combination with licensed antiretroviral medications.
This study aims to demonstrate that patients substituting raltegravir for a PI or NNRTI based antiretroviral regimen will be associated with a 10% reduction in body fat over 24 weeks.
The study will consist of a total of 10 subject visits over a period of 48 weeks. Approximately 40 female patients will participate in this study (approximately 10 at UCLA).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immediate | Active comparator | Drug: raltegravirImmediate switch of PI or NNRTI to Raltegravir |
| Delayed | Active comparator | Drug: raltegravirContinue current therapy unchanged for 24 weeks, then switch PI or NNRTI to Raltegravir |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- HIV-1 infection as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry or plasma HIV-1 RNA > 2000 on two occasions,
- Female subjects 18 years or older
- Documented central fat accumulation (defined by waist circumference of > 94 cm or a waist to hip ratio of > 0.88).
- Documented HIV RNA <50 copies/mL at screening and <400 copies/mL in the past 6 months.
- Current antiretroviral therapy with two nucleoside analogues and either a non-nucleoside analogue (nevirapine, efavirenz or TMC125) or an approved protease inhibitor. Patients on NNRTI+PI at study entry will be excluded. Study participants do not need to be on their first regimen. No changes in ART in the 12 weeks prior to screening. The nucleoside backbone must include either tenofovir or abacavir and either lamivudine or emtricitabine. Fixed dose combinations with emtricitabine or abacavir are allowed.
Key exclusion criteria (13 listed)
- Pregnancy: current or within the past 6 months or breast feeding
- Prior treatment history that would preclude the use of emtricitabine or abacavir as the nucleoside backbone during study treatment
- Current use of metformin or thiazolidinediones.
- Use of growth hormone or growth hormone releasing factor in the last 6 months before screening.
- Change or initiation of anti-hyperlipemic regimen within 3 months prior to randomization; Use of stable anti-hyperlipemic regimen during the study is allowed.
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 |
|---|---|---|
| raltegravirAlso: Isentressraltegravir | Drug | Delayed, Immediate |
Primary outcome
Baseline to 24-week Change in Visceral Adipose Tissue Volume (cm^2)
Time frame: Baseline and 24 weeks
Adipose tissue volumes were measured via single slice L4-L5 CT scan, and volumes were calculated using cm^2, not cm^3, as is standard protocol at the Tufts University Body Composition Reading Center. The authors acknowledge that cm^2 uses area as a surrogate for volume, but this protocol is well-accepted in our field.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22823027Lake JE, McComsey GA, Hulgan TM, Wanke CA, Mangili A, Walmsley SL, Boger MS, Turner RR, McCreath HE, Currier JS. A randomized trial of Raltegravir replacement for protease inhibitor or non-nucleoside reverse transcriptase inhibitor in HIV-infected women with lipohypertrophy. AIDS Patient Care STDS. 2012 Sep;26(9):532-40. doi: 10.1089/apc.2012.0135. Epub 2012 Jul 23.
- Derived from this study: PubMed 29746485Offor O, Utay N, Reynoso D, Somasunderam A, Currier J, Lake J. Adiponectin and the steatosis marker Chi3L1 decrease following switch to raltegravir compared to continued PI/NNRTI-based antiretroviral therapy. PLoS One. 2018 May 10;13(5):e0196395. doi: 10.1371/journal.pone.0196395. eCollection 2018.
Related trials for HIV Infections
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
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.
Judith S. Currier, M.D. principal investigator
University of California, Los Angeles
Grace McComsey, M.D. study chair
Case School of Medicine
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing raltegravir in people with HIV Infections and Lipodystrophy, run by University of California, Los Angeles at 5 sites in 2 countries.
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 13 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 19 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Canada. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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.
What does the primary outcome measure?
Baseline to 24-week Change in Visceral Adipose Tissue Volume (cm^2) (time frame: Baseline and 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00656175, which also lists 2 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 19 Dec 2012.