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Raltegravir Therapy for Women With HIV and Fat Accumulation

Primary Purpose

HIV Infections, Lipodystrophy

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

raltegravir

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring lipodystrophy, fat, visceral fat, HIV, women, raltegravir, ART, anti HIV therapy, NNRTI, Protease inhibitor, integrase inhibitor, treatment experienced

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.
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

Sites / Locations

UCLA CARE Center
Tufts University School of Medicine
Case School of Medicine
Vanderbilt University
University Health Network, Toronto

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Immediate

Delayed

Arm Description

Immediate switch of PI or NNRTI to Raltegravir

Continue current therapy unchanged for 24 weeks, then switch PI or NNRTI to Raltegravir

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT00656175

First Posted

April 2, 2008

Last Updated

December 17, 2012

Sponsor

University of California, Los Angeles

Collaborators

Merck Sharp & Dohme LLC, Case Western Reserve University, Vanderbilt University, Tufts University, University Health Network, Toronto

1. Study Identification

Unique Protocol Identification Number

NCT00656175

Brief Title

Raltegravir Therapy for Women With HIV and Fat Accumulation

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2012

Overall Recruitment Status

Completed

Study Start Date

September 2008 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, Los Angeles

Collaborators

Merck Sharp & Dohme LLC, Case Western Reserve University, Vanderbilt University, Tufts University, University Health Network, Toronto

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections, Lipodystrophy

Keywords

lipodystrophy, fat, visceral fat, HIV, women, raltegravir, ART, anti HIV therapy, NNRTI, Protease inhibitor, integrase inhibitor, treatment experienced

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Immediate

Arm Type

Active Comparator

Arm Description

Immediate switch of PI or NNRTI to Raltegravir

Arm Title

Delayed

Arm Type

Active Comparator

Arm Description

Continue current therapy unchanged for 24 weeks, then switch PI or NNRTI to Raltegravir

Intervention Type

Drug

Intervention Name(s)

raltegravir

Other Intervention Name(s)

Isentress

Intervention Description

raltegravir

Primary Outcome Measure Information:

Title

Baseline to 24-week Change in Visceral Adipose Tissue Volume (cm^2)

Description

Time Frame

Baseline and 24 weeks

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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. 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Judith S. Currier, M.D.

Organizational Affiliation

University of California, Los Angeles

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Grace McComsey, M.D.

Organizational Affiliation

Case School of Medicine

Official's Role

Study Chair

Facility Information:

Facility Name

UCLA CARE Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90035

Country

United States

Facility Name

Tufts University School of Medicine

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02111

Country

United States

Facility Name

Case School of Medicine

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106

Country

United States

Facility Name

Vanderbilt University

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

University Health Network, Toronto

City

Toronto

State/Province

Ontario

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

22823027

Citation

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.

Results Reference

result

PubMed Identifier

29746485

Citation

Offor 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.

Results Reference

derived

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Raltegravir Therapy for Women With HIV and Fat Accumulation

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