Ignite Creation Date:
2024-05-05 @ 11:03 PM
Last Modification Date:
2024-10-26 @ 10:28 AM
Study NCT ID:
NCT01245101
Status:
TERMINATED
Last Update Posted:
2016-12-23
First Post:
2010-11-19
Brief Title:
Addition of Raltegravir to Established Antiretroviral Suppressive Therapy
Sponsor:
University of Miami
Organization:
University of Miami
Study Overview
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
Status:
TERMINATED
Status Verified Date:
2016-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Poor enrollment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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 copiesml by RT-PCR or 75 copiesml by bDNA assay and CD4 count of 350 cellsmm3 or an increase in CD4count 100 cellsmm3 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 11 and no higher than 2 NNRTI1 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
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 11 and no higher than 2 NNRTI1 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None