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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT01245101
Other study ID # UM 20100499
Secondary ID
Status Active, not recruiting
Phase Phase 4
First received November 19, 2010
Last updated June 1, 2015
Start date November 2010
Est. completion date October 2015

Study information

Verified date June 2015
Source University of Miami
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 40
Est. completion date October 2015
Est. primary completion date October 2012
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Raltegravir
Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.
Raltegravir
Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.

Locations

Country Name City State
United States Infectious Diseases Research Unit, University of Miami Miller School of Medicine Miami Florida

Sponsors (2)

Lead Sponsor Collaborator
University of Miami Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Episomal HIV cDNA formation 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. 40 weeks No
Secondary Markers of immune activation 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. 40 weeks No
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