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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00672932
• Other study ID #: CCRC5004
• Secondary ID: R01MH062701
• Status: Completed
• Phase: N/A
• First received: April 29, 2008
• Last updated: May 29, 2013
• Start date: April 2008
• Est. completion date: February 2011

Study information

• Verified date: May 2013
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: February 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• raltegravir
400 mg two times daily for three months

Locations

Country	Name	City	State
United States	Ucsf Ccrc, Sfgh	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	Merck Sharp & Dohme Corp., National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Dahl V, Lee E, Peterson J, Spudich SS, Leppla I, Sinclair E, Fuchs D, Palmer S, Price RW. Raltegravir treatment intensification does not alter cerebrospinal fluid HIV-1 infection or immunoactivation in subjects on suppressive therapy. J Infect Dis. 2011 D — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in CSF Concentrations of Neopterin After 12 Weeks	CSF markers of immuno¬activation and inflammation after 12 weeks compared to baseline.	three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)	No
Secondary	Change From Baseline in CD8+ T Cell Co-expression of CD38 and HLA-DR	Blood CD8+ T cell activation as indicated by percentage of cells in fresh specimens coexpressing surface CD38 and human leukocyte antigen (HLA)-DR.	three months (Rollover subjects were assessed for a second baseline after the initial 12 week period)	No