Addition of Raltegravir to Established Antiretroviral Suppressive Therapy

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2010 by University of Miami.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
University of Miami
ClinicalTrials.gov Identifier:
NCT01245101
First received: November 19, 2010
Last updated: NA
Last verified: November 2010
History: No changes posted
  Purpose

This study will examine whether intensification with raltegravir of a suppressive antiretroviral regimen in HIV infected patients with poor immune restoration has a beneficial effect on cryptic viral replication and the immune system. Specifically, the investigators will examine the effect that raltegravir intensification of ART has on episomal cDNA frequencies, immune activation, CD4+ cell counts and apoptosis, and markers of microbial translocation.


Condition Intervention Phase
HIV
Drug: Raltegravir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Open-Label, Double-Arm, Crossover, Single-Center Pilot Study to Evaluate the Addition of Raltegravir to Established Suppressive Antiretroviral Therapy While Monitoring Changes in Markers of Immune Activation Among HIV-1 Infected Individuals Without Adequate Immune Restoration

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Episomal HIV cDNA formation [ Time Frame: 40 weeks ] [ Designated as safety issue: No ]
    These are linear viral cDNAs that are subsequently circularized by the DNA repair apparatus of the host cell to form episomes. They are markers of ongoing viral replication.


Secondary Outcome Measures:
  • Markers of immune activation [ Time Frame: 40 weeks ] [ Designated as safety issue: No ]
    Flow cytometry will be performed in whole blood for analysis of markers CD3, CD4, CD8, HLA-DR and CD38 by standard methodology using a LSR-II flow cytometer. Percentage and absolute counts of CD3+CD4+T cells, and frequencies of CD3+CD8+ subset, CD8+CD38+; CD8+ HLA-DR+ and CD8+HLADR+ CD38+ cells will be determined.


Estimated Enrollment: 40
Study Start Date: January 2011
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
The total duration of the study will be 40 weeks. This will include Part 1 (16 weeks) followed by Part 2 (8 weeks) followed by the crossover to Part 2 (16 weeks). During Part 1 participants in Group A will receive open-label raltegravir in addition to their established antiretroviral regimen while Group B participants will continue taking their established antiretroviral regimen for 16 weeks. After completion of Part 1, both groups will enter Part 2 that will consist of a washout period of 8 weeks during which both groups will only take their established antiretroviral regimen without raltegravir. This will be followed by Part 3 during which the two study groups will undergo a crossover with respect to the treatment assignment during Part 1 so that Group A will continue to receive their established antiretroviral regimen while Group B will receive open-label raltegravir in addition to their established antiretroviral regimen for 16 weeks.
Drug: Raltegravir
Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.
Active Comparator: Group B
The total duration of the study will be 40 weeks. This will include Part 1 (16 weeks) followed by Part 2 (8 weeks) followed by the crossover to Part 2 (16 weeks). During Part 1 participants in Group A will receive open-label raltegravir in addition to their established antiretroviral regimen while Group B participants will continue taking their established antiretroviral regimen for 16 weeks. After completion of Part 1, both groups will enter Part 2 that will consist of a washout period of 8 weeks during which both groups will only take their established antiretroviral regimen without raltegravir. This will be followed by Part 3 during which the two study groups will undergo a crossover with respect to the treatment assignment during Part 1 so that Group A will continue to receive their established antiretroviral regimen while Group B will receive open-label raltegravir in addition to their established antiretroviral regimen for 16 weeks.
Drug: Raltegravir
Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.

Detailed Description:

This is a single-center, open-label, double-arm, crossover study which will include approximately 40 HIV-infected subjects on an established suppressive HAART for at least 2 years with evidence of undetectable HIV-1 RNA levels (either <50 copies/ml by RT-PCR or <75 copies/ml by bDNA assay) and CD4+ count of <350 cells/mm3 or an increase in CD4+count <100 cells/mm3 in the last 2 years. Participants (~20 Group 1 and ~20 in Group 2) will be randomly assigned to 1 of the 2 treatment arms described below in Table 1:

Table 1. Study groups and treatment assignments

Group A Raltegravir 400 mg PO q12h in addition to established ART (Part 1) followed by a washout period only on ART (Part 2) followed by ART (Part 3)

Group B Established ART (Part 1) followed by a washout period only on ART (Part 2) followed by raltegravir 400 mg PO q12h in addition to ART (Part 3)

The participants' pre-study HAART will be monitored so as to ensure that the distribution of NNRTI to PI-based regimens is roughly 1:1 and no higher than 2 (NNRTI):1 (PI).

The total duration of the study will be 40 weeks. This will include Part 1 (16 weeks) followed by Part 2 (8 weeks) followed by the crossover to Part 2 (16 weeks) (Figure 1). During Part 1 participants in Group A will receive open-label raltegravir in addition to their established antiretroviral regimen while Group B participants will continue taking their established antiretroviral regimen for 16 weeks. After completion of Part 1, both groups will enter Part 2 that will consist of a washout period of 8 weeks during which both groups will only take their established antiretroviral regimen without raltegravir. This will be followed by Part 3 during which the two study groups will undergo a crossover with respect to the treatment assignment during Part 1 so that Group A will continue to receive their established antiretroviral regimen while Group B will receive open-label raltegravir in addition to their established antiretroviral regimen for 16 weeks.

After obtaining informed consent, patients will be enrolled into the study, a study number will be assigned, a complete history will be obtained, and a physical exam will be performed. Blood will be drawn for the following laboratory exams at Day 1 and at Weeks 1, 2, 4, 10, 16, 24, 25 26, and 40 for Group A and at Day 1 and at Weeks 1, 2, 16, 24, 25, 26, 28, 34, and 40 for Group B:

  • T-cell subsets
  • Plasma viral load
  • Episomal viral cDNA PCR
  • HLA-DR levels
  • CD38 levels

Blood will also be drawn for the following laboratory exams at Day 1 and at Weeks 4, 12, 16, 24, 28, 36, and 40 for both Group A and Group B to determine

  • Plasma levels of LPS, 16s ribosomal DNA, and sCD14
  • T cell receptor excision circles
  • CD4+ and CD8+ T-cell apoptosis

At all visits, a directed physical exam will be performed on an as-needed-basis.

  Eligibility

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

Inclusion Criteria:

To qualify for this study, participants will need to have:

  1. At least 18 years of age
  2. Documented HIV-1 infection
  3. CD4+ count <350 cells/mm3 at the time of enrollment or CD4+ count increase of <100 cells/mm3 within the past 2 years
  4. Plasma viral load <400 copies/ml at all testing time points within the preceding 2 years AND <50 copies/ml by RT-PCR or <75 copies/ml by bDNA at the 2 testing time points immediately preceding enrollment into the study

Exclusion Criteria:

To qualify for this study, patients must not meet any of the following exclusion criteria:

  1. Pregnancy or breast-feeding
  2. Prior use of raltegravir at any time in the past
  3. Use of any investigational, immunomodulatory, immunosuppressive agents within 90 days prior or during this study
  4. Alcohol or substance abuse that in the opinion of the investigator might interfere with patient compliance or safety
  5. Any condition or pre-study laboratory abnormality that in the opinion of the investigator might interfere with patient compliance or safety
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01245101

Contacts
Contact: Tom Tanner, RN 305-243-5621
Contact: Rafael E Campo, MD 305-243-3006

Locations
United States, Florida
Infectious Diseases Research Unit, University of Miami Miller School of Medicine Not yet recruiting
Miami, Florida, United States, 33136
Contact: Tom Tanner, RN    305-243-5621    ttanner@med.miami.edu   
Principal Investigator: Rafael E Campo, MD         
Infectious Diseases Research Unit, University of Miami Miller School of Medicine Not yet recruiting
Miami, Florida, United States, 33136
Contact: Tom Tanner, RN    305-243-5621    ttanner@med.miami.edu   
Sponsors and Collaborators
University of Miami
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Rafael E Campo, MD University of Miami
  More Information

No publications provided

Responsible Party: Rafael E. Campo, MD, University of Miami Miller School of Medicine
ClinicalTrials.gov Identifier: NCT01245101     History of Changes
Other Study ID Numbers: UM 20100499
Study First Received: November 19, 2010
Last Updated: November 19, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
HIV raltegravir intensification replication activation

ClinicalTrials.gov processed this record on April 21, 2014