Raltegravir Therapy for Women With HIV and Fat Accumulation

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00656175
• Other study ID #: IISP-Raltegravir
• Status: Completed
• Phase: Phase 2
• First received: April 2, 2008
• Last updated: December 17, 2012
• Start date: September 2008
• Est. completion date: December 2011

Study information

• Verified date: December 2012
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical 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. 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).

Other known NCT identifiers

• NCT00755612

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Lipodystrophy

Intervention

Drug:
• raltegravir
raltegravir

Locations

Country	Name	City	State
Canada	University Health Network, Toronto	Toronto	Ontario
United States	Tufts University School of Medicine	Boston	Massachusetts
United States	Case School of Medicine	Cleveland	Ohio
United States	UCLA CARE Center	Los Angeles	California
United States	Vanderbilt University	Nashville	Tennessee

Sponsors (6)

Lead Sponsor	Collaborator
University of California, Los Angeles	Case Western Reserve University, Merck Sharp & Dohme Corp., Tufts University, University Health Network, Toronto, Vanderbilt University

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 w — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline and 24 weeks	No