Raltegravir Therapy for Women With HIV and Fat Accumulation

• ClinicalTrials.gov Identifier: NCT00656175
• Recruitment Status: Completed
• First Posted: April 10, 2008
• Results First Posted: December 19, 2012
• Last Update Posted: December 19, 2012
• Sponsor: University of California, Los Angeles
• Collaborators: Merck Sharp & Dohme LLC; 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

Tracking Information

• First Submitted Date: April 2, 2008
• First Posted Date: April 10, 2008
• Results First Submitted Date: June 12, 2012
• Results First Posted Date: December 19, 2012
• Last Update Posted Date: December 19, 2012
• Study Start Date: September 2008
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 17, 2012)

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.

• Original Primary Outcome Measures (submitted: April 4, 2008): 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 ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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).

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• HIV Infections
• Lipodystrophy

Intervention

Drug: raltegravir

raltegravir

Other Name: Isentress

Study Arms

• Active Comparator: Immediate
  Immediate switch of PI or NNRTI to Raltegravir
  Intervention: Drug: raltegravir
• Active Comparator: Delayed
  Continue current therapy unchanged for 24 weeks, then switch PI or NNRTI to Raltegravir
  Intervention: Drug: raltegravir

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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 17, 2012): 39
• Original Estimated Enrollment (submitted: April 4, 2008): 40
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00656175
• Other Study ID Numbers: IISP-Raltegravir
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Judith S. Currier, University of California, Los Angeles
• Original Responsible Party: Judith S. Currier, M.D., UCLA
• Current Study Sponsor: University of California, Los Angeles
• Original Study Sponsor: Same as current

Collaborators

• Merck Sharp & Dohme LLC
• 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

• PRS Account: University of California, Los Angeles
• Verification Date: December 2012