Raltegravir Therapy for Women With HIV and Fat Accumulation

This study has been completed.
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Case Western Reserve University
Vanderbilt University
Tufts University
University Health Network, Toronto
Information provided by (Responsible Party):
Judith S. Currier, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT00656175
First received: April 2, 2008
Last updated: December 17, 2012
Last verified: December 2012
  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 2

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Baseline to 24-week Change in Visceral Adipose Tissue Volume (cm^2) [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 39
Study Start Date: September 2008
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Immediate
Immediate switch of PI or NNRTI to Raltegravir
Drug: raltegravir
raltegravir
Other Name: Isentress
Active Comparator: Delayed
Continue current therapy unchanged for 24 weeks, then switch PI or NNRTI to Raltegravir
Drug: raltegravir
raltegravir
Other Name: Isentress

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
UCLA CARE Center
Los Angeles, California, United States, 90035
United States, Massachusetts
Tufts University School of Medicine
Boston, Massachusetts, United States, 02111
United States, Ohio
Case School of Medicine
Cleveland, Ohio, United States, 44106
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37203
Canada, Ontario
University Health Network, Toronto
Toronto, Ontario, Canada
Sponsors and Collaborators
University of California, Los Angeles
Merck Sharp & Dohme Corp.
Case Western Reserve University
Vanderbilt University
Tufts University
University Health Network, Toronto
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

Publications:
Responsible Party: Judith S. Currier, M.D., University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00656175     History of Changes
Obsolete Identifiers: NCT00755612
Other Study ID Numbers: IISP-Raltegravir
Study First Received: April 2, 2008
Results First Received: June 12, 2012
Last Updated: December 17, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Los Angeles:
lipodystrophy
fat
visceral fat
HIV
women
raltegravir
ART
anti HIV therapy
NNRTI
Protease inhibitor
integrase inhibitor
treatment experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lipodystrophy
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Protease Inhibitors
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 18, 2014