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Raltegravir Cerebrospinal Fluid Pharmacodynamic Study in HIV-Infected Individuals

This study is currently recruiting participants.
Verified January 2012 by University of California, San Diego
Sponsor:
Collaborator:
Merck
Information provided by (Responsible Party):
Scott Letendre, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT01293123
First received: February 9, 2011
Last updated: January 9, 2012
Last verified: January 2012
History of Changes
  Purpose

The primary aim of this study is to determine the effects of the HIV integrase inhibitor, raltegravir, in cerebrospinal fluid (CSF). This will be accomplished by collecting CSF before and after initiation of either raltegravir or another antiretroviral, efavirenz, each in combination with two other antiretrovirals. Assessments will include HIV RNA levels (viral load), neuropsychological testing, mood assessments, and quality of life assessments.


Condition Intervention
HIV
 Drug: Raltegravir
Drug: Efavirenz

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Raltegravir Cerebrospinal Fluid Pharmacodynamic Study in HIV-Infected Individuals

Resource links provided by NLM:

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

Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • Cerebrospinal fluid HIV RNA levels [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    Slope of decline of HIV RNA levels in CSF over time


Secondary Outcome Measures:
  • Neuropsychological performance [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    Change in neuropsychological performance over 180 days

  • Measure of mood [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    Change in mood over 180 days

  • Measure of sleep [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    Change in self-reported sleep performance over 180 days.

  • Measure of quality of life [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    Change in self-report quality of life over 180 days


Estimated Enrollment: 15
Study Start Date: December 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Raltegravir Drug: Raltegravir
raltegravir 400 mg PO twice daily
Other Names:
  • tenofovir disoproxil fumarate 300 mg PO once daily
  • emtricitabine 200 mg PO once daily
Active Comparator: Efavirenz Drug: Efavirenz
efavirenz 600 mg PO once daily
Other Names:
  • tenofovir disoproxil fumarate 300 mg PO once daily
  • emtricitabine 200 mg PO once daily

Detailed Description:

Cognitive disorders continue to be a common complication of HIV disease even though potent antiretroviral drugs can reduce HIV below detectable levels and restore immune function. Concentrations of most antiretrovirals in the nervous system are only a fraction of concentrations in blood. As a result, HIV can continue to be present in the nervous system when it is below detection in blood. A recently approved drug, raltegravir, reaches therapeutic concentrations in cerebrospinal fluid and may be effective at controlling HIV replication in the primary target cells in the brain, macrophages and microglia. Based on this, raltegravir may be a particularly effective drug for treating HIV disease in the nervous system. The purpose of this study is to determine the effects of raltegravir in the nervous system by measuring HIV in the CSF (via lumbar puncture, also known as spinal taps) before and after initiation of raltegravir-containing antiretroviral therapy. CSF is an accessible fluid that provides a window into brain processes, including HIV replication and inflammation. The potency of raltegravir will be estimated by calculating the change in HIV viral load in CSF over time. These changes will be compared to those following initiation an efavirenz-containing regimen in a separate group of individuals. Two additional drugs (tenofovir disoproxil fumarate, emtricitabine) will be combined with either raltegravir or efavirenz. Neuropsychological performance, mood, sleep and quality of life assessment will also be compared. Participants will be randomly assigned to either raltegravir- or efavirenz-containing therapy.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men and women aged 18-65 years;
  2. Integrase inhibitor-naive subjects with clinical indication to initiate RAL under the supervision of their HIV care provider;
  3. Baseline detectable HIV-1 RNA levels ≥ 5000 copies/mL in plasma and ≥ 500 copies/mL in CSF;
  4. Absolute T-cell CD4+ subset between 200-500/mm3
  5. Individual willing to undergo serial lumbar punctures as outlined in study evaluations;
  6. Subject able to give informed consent to all study procedures (if cognitively impaired, the individual must pass an evaluation to ensure adequate comprehension of the consent document and procedures);
  7. Susceptibility to all study drugs on Monogram Biosciences PhenoSense GT assay.

Exclusion Criteria:

  1. Contraindication to lumbar puncture, such as current coagulopathy, thrombocytopenia (platelets below 50,000/µL), or use of anticoagulants;
  2. Cognitive, psychiatric, or substance use disorders or any other medical conditions that would interfere with study participation, in the opinion of the investigator;
  3. Major opportunistic infections (e.g., pneumonia, tuberculosis) within 30 days;
  4. Use of prescribed drugs with known substantial interactions with the study drugs;
  5. Positive HCV serology;
  6. HIV-associated dementia/Global Deterioration Scale ≥4;
  7. Pregnancy;
  8. Serum creatinine higher than 2.0 mg/dL;
  9. Total bilirubin or alanine or aspartate transaminases more than 3 times the upper limit of normal
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01293123

Contacts
Contact: Scott Letendre, MD 619-543-4730 sletendre@ucsd.edu
Contact: David Croteau, MD 619-543-4755 dcroteau@ucsd.edu

Locations
United States, California
UCSD Antiviral Research Center Recruiting
San Diego, California, United States, 92103
Contact: Scott Letendre, MD     619-543-4730     sletendre@ucsd.edu    
Contact: David Croteau, MD     619-543-4755     dcroteau@ucsd.edu    
Principal Investigator: Letendre Scott, MD            
Sub-Investigator: David Croteau, MD            
Sponsors and Collaborators
University of California, San Diego
Merck
Investigators
Principal Investigator: Scott Letendre, MD University of California, San Diego
  More Information

No publications provided

Responsible Party: Scott Letendre, Associate Professor of Medicine, University of California, San Diego
ClinicalTrials.gov Identifier: NCT01293123     History of Changes
Other Study ID Numbers: 11-0067
Study First Received: February 9, 2011
Last Updated: January 9, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Diego:
HIV
raltegravir
cerebrospinal fluid

Additional relevant MeSH terms:
Tenofovir
Tenofovir disoproxil
Efavirenz
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on May 19, 2013