Raltegravir Therapy for Women With HIV and Fat Accumulation - Full Text View

Sponsor:	University of California, Los Angeles
Collaborators:	Merck Case Western Reserve University Vanderbilt University Tufts University AltaMed Health Services
Information provided by:	University of California, Los Angeles
ClinicalTrials.gov Identifier:	NCT00656175

Purpose

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).

Condition	Intervention	Phase
HIV Infections Lipodystrophy	Drug: raltegravir	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase II Study of Raltegravir as Replacement for Protease Inhibitor or Non-Nucleoside Reverse Transcriptase Inhibitor Based Antiretroviral Therapy in Women With Fat Accumulation

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Raltegravir

U.S. FDA Resources

Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:

Compared to continued treatment with a PI and/or NNRTI based regimen, substituting raltegravir will be associated with a 10% reduction in visceral adipose tissue over 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	August 2008
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm A: Active Comparator Immediate switch of PI or NNRTI to raltegravir	Drug: raltegravir raltegravir
Arm B: Active Comparator Continue current therapy unchanged for 24 weeks then switch PI or NNRTI to raltegravir	Drug: raltegravir raltegravir

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00656175

Locations

United States, California
UCLA CARE Center	Recruiting
Los Angeles, California, United States, 90035
Contact: Maricela Gonzalez 310-557-3798 mgonzalez@mednet.ucla.edu
Contact: Irma Franco-Gonzalez 310-557-1895
Principal Investigator: Judith Currier, M.D.
Sub-Investigator: Jordan Lake, M.D.
Altamed Health Services Corporation	Not yet recruiting
Los Angeles, California, United States, 90022
Contact: Neisha Opper 323-869-5415 neisha@kenmarresearch.com
Contact: Roxana Garcia 323-869-5415
Principal Investigator: Daniel Pearce, D.O.
United States, Massachusetts
Tufts University School of Medicine	Not yet recruiting
Boston, Massachusetts, United States, 02111
Contact: Jul Gerrior 617-636-0492 jul.gerrior@tufts.edu
Principal Investigator: Christine Wanke, M.D.
United States, Ohio
Case School of Medicine	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Dawn Antosh, R.N. 216-844-1392 antosh.dawn@clevelandactu.org
Contact: Jane Baum, R.N. 216-844-2546 baum.jane@clevelandactu.org
Principal Investigator: Grace McComsey, M.D.
United States, Tennessee
Vanderbilt University	Not yet recruiting
Nashville, Tennessee, United States, 37203
Principal Investigator: Todd Hulgan, M.D.

Sponsors and Collaborators

University of California, Los Angeles

Merck

Case Western Reserve University

Vanderbilt University

Tufts University

AltaMed Health Services

Investigators

Principal Investigator:	Judith S. Currier, M.D.	University of California, Los Angeles
Study Chair:	Grace McComsey, M.D.	Case School of Medicine

More Information

No publications provided

Responsible Party:	UCLA ( Judith S. Currier, M.D. )
Study ID Numbers:	IISP-Raltegravir
Study First Received:	April 2, 2008
Last Updated:	January 23, 2009
ClinicalTrials.gov Identifier:	NCT00656175 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of California, Los Angeles:

raltegravir
lipodystrophy
fat
visceral fat
HIV
women

ART
anti HIV therapy
NNRTI
Protease inhibitor
integrase inhibitor
treatment experienced

Additional relevant MeSH terms:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lipodystrophy
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections
Metabolic Diseases
Immune System Diseases

Skin Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases
HIV Infections
Skin Diseases, Metabolic
Sexually Transmitted Diseases
Lentivirus Infections
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on February 08, 2010