Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients
This study has been completed.
Sponsor:
University of California, San Francisco
Collaborators:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00672932
First received: April 29, 2008
Last updated: May 29, 2013
Last verified: May 2013
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Purpose
This pilot study focuses on the persistence of central nervous system (CNS) immune activation that has been observed in the presence of 'effective' combination antiretroviral therapy (cART). Attention to this issue is based on the fear that chronic CNS immunoactivation can cause indolent brain injury that will eventually compromise brain function as patients survive for years on treatment. A leading hypothesis explaining this continued immunoactivation is that viral replication continues within the brain at a level too low for detection in cerebrospinal fluid (CSF), yet sufficient to stimulate local immunoactivation. Based on this hypothesis, we propose to use augmented treatment with raltegravir to test whether additional suppression of this hypothesized CNS HIV-1 replication will reduce continued CNS immunoactivation.
| Condition | Intervention |
|---|---|
|
HIV Infections |
Drug: raltegravir |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label |
| Official Title: | Pilot Study of Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients |
Resource links provided by NLM:
Further study details as provided by University of California, San Francisco:
Primary Outcome Measures:
- Change in CSF Concentrations of Neopterin After 12 Weeks [ Time Frame: three months (Rollover subjects were assessed for a second baseline after the initial 12 week period) ] [ Designated as safety issue: No ]CSF markers of immuno¬activation and inflammation after 12 weeks compared to baseline.
Secondary Outcome Measures:
- Change From Baseline in CD8+ T Cell Co-expression of CD38 and HLA-DR [ Time Frame: three months (Rollover subjects were assessed for a second baseline after the initial 12 week period) ] [ Designated as safety issue: No ]Blood CD8+ T cell activation as indicated by percentage of cells in fresh specimens coexpressing surface CD38 and human leukocyte antigen (HLA)-DR.
| Enrollment: | 18 |
| Study Start Date: | April 2008 |
| Study Completion Date: | February 2011 |
| Primary Completion Date: | October 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: raltegravir group
The raltegravir dosing will be 400mg twice daily by mouth. Subjects will continue all of their regular medications throughout the protocol.
|
Drug: raltegravir
400 mg two times daily for three months
Other Name: Isentress
|
|
No Intervention: No augmented treatment
Subjects randomized not to receive augmented treatment will continue in the study with their regular antiretroviral regimen.
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Capacity to provide informed consent.
- Documented HIV-1 infection.
- History of continuous cART treatment (with at least three drugs) for at least 2 years.
- Documentation of 'undetectable' plasma HIV-1 RNA for at least 1 year.
- HIV-1 RNA <50 copies/mL in plasma and CSF at screening visit.
Exclusion Criteria:
- Contraindication to LP (suspicion of CNS mass lesion, bleeding diathesis, etc.).
- Prior experience with raltegravir or contraindication to raltegravir treatment, including medication interactions that might compromise ongoing antiretroviral therapy or treatment of other conditions.
- Active opportunistic infections or neurological diseases.
- Other conditions or treatments likely to interfere with treatment or evaluation.
- Hemoglobin < 10 Gm/dL.
- Pregnant or anticipating pregnancy during study.
- Active substance abuse.
- Subjects taking rifampin, phenytoin, Phenobarbital or other drugs that accelerate raltegravir metabolism and might decrease its tissue concentrations.
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00672932
Please refer to this study by its ClinicalTrials.gov identifier: NCT00672932
Locations
| United States, California | |
| Ucsf Ccrc, Sfgh | |
| San Francisco, California, United States, 94110 | |
Sponsors and Collaborators
University of California, San Francisco
Merck Sharp & Dohme Corp.
Investigators
| Principal Investigator: | Richard Price, MD | University of California, San Francisco |
More Information
Publications:
| Responsible Party: | University of California, San Francisco |
| ClinicalTrials.gov Identifier: | NCT00672932 History of Changes |
| Other Study ID Numbers: | CCRC5004, R01 MH 62701 |
| Study First Received: | April 29, 2008 |
| Results First Received: | June 18, 2012 |
| Last Updated: | May 29, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by University of California, San Francisco:
|
raltegravir central nervous system (CNS) HIV-1 AIDS |
cerebrospinal fluid (CSF) immunoactivation antiretroviral therapy suppression |
ClinicalTrials.gov processed this record on March 03, 2015