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

This study has been completed.
Sponsor:
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
  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
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, see Learn About Clinical Studies.

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

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on September 18, 2014