- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01245101
Addition of Raltegravir to Established Antiretroviral Suppressive Therapy
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
Study Overview
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Florida
-
Miami, Florida, United States, 33136
- Infectious Diseases Research Unit, University of Miami Miller School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
To qualify for this study, participants will need to have:
- At least 18 years of age
- Documented HIV-1 infection
- CD4+ count <350 cells/mm3 at the time of enrollment or CD4+ count increase of <100 cells/mm3 within the past 2 years
- 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:
- Pregnancy or breast-feeding
- Prior use of raltegravir at any time in the past
- Use of any investigational, immunomodulatory, immunosuppressive agents within 90 days prior or during this study
- Alcohol or substance abuse that in the opinion of the investigator might interfere with patient compliance or safety
- Any condition or pre-study laboratory abnormality that in the opinion of the investigator might interfere with patient compliance or safety
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Raltegravir and then Observation
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.
|
Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.
|
Active Comparator: Observation and then Raltegravir
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.
|
Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Episomal HIV cDNA Formation
Time Frame: 16 weeks
|
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.
|
16 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Markers of Immune Activation
Time Frame: 16 weeks
|
Flow cytometry will be performed in whole blood for analysis of markers of immune activation by standard methodology using a LSR-II flow cytometer.
Percentage and absolute counts of CD8+CD38+ cells will be determined as the main outcome measure.
|
16 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Rafael E Campo, MD, University of Miami
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20100499
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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