ClinicalTrials.gov
ClinicalTrials.gov Menu

Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00672932
Recruitment Status : Completed
First Posted : May 6, 2008
Results First Posted : July 5, 2013
Last Update Posted : July 5, 2013
Sponsor:
Collaborators:
National Institute of Mental Health (NIMH)
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of California, San Francisco

Study Description
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
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 or disease Intervention/treatment Phase
HIV Infections Drug: raltegravir Not Applicable

Study Design
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: Pilot Study of Raltegravir Augmentation on Persistent Central Nervous System (CNS) Immunoactivation in Treated HIV-1 Patients
Study Start Date : April 2008
Actual Primary Completion Date : October 2010
Actual Study Completion Date : February 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arms and Interventions
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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.


Outcome Measures
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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) ]
    CSF markers of immuno¬activation and inflammation after 12 weeks compared to baseline.


Secondary Outcome Measures :
  1. 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) ]
    Blood CD8+ T cell activation as indicated by percentage of cells in fresh specimens coexpressing surface CD38 and human leukocyte antigen (HLA)-DR.


Eligibility Criteria
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00672932


Locations
United States, California
Ucsf Ccrc, Sfgh
San Francisco, California, United States, 94110
Sponsors and Collaborators
University of California, San Francisco
National Institute of Mental Health (NIMH)
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Richard Price, MD University of California, San Francisco
More Information
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00672932     History of Changes
Other Study ID Numbers: CCRC5004
R01MH062701 ( U.S. NIH Grant/Contract )
First Posted: May 6, 2008    Key Record Dates
Results First Posted: July 5, 2013
Last Update Posted: July 5, 2013
Last Verified: May 2013

Keywords provided by University of California, San Francisco:
raltegravir
central nervous system (CNS)
HIV-1
AIDS
 cerebrospinal fluid (CSF)
immunoactivation
antiretroviral therapy
suppression

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
 Raltegravir Potassium
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action