Raltegravir Cerebrospinal Fluid Pharmacodynamic Study in HIV-Infected Individuals

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by University of California, San Diego.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
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

February 9, 2011
January 9, 2012
December 2011
June 2013   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01293123 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Raltegravir Cerebrospinal Fluid Pharmacodynamic Study in HIV-Infected Individuals
Raltegravir Cerebrospinal Fluid Pharmacodynamic Study in HIV-Infected Individuals

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV
  • Drug: Raltegravir
    raltegravir 400 mg PO twice daily
    Other Names:
    • tenofovir disoproxil fumarate 300 mg PO once daily
    • emtricitabine 200 mg PO once daily
  • Drug: Efavirenz
    efavirenz 600 mg PO once daily
    Other Names:
    • tenofovir disoproxil fumarate 300 mg PO once daily
    • emtricitabine 200 mg PO once daily
  • Experimental: Raltegravir
    Intervention: Drug: Raltegravir
  • Active Comparator: Efavirenz
    Intervention: Drug: Efavirenz
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
15
December 2013
June 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
No
Contact: Scott Letendre, MD 619-543-4730 sletendre@ucsd.edu
Contact: David Croteau, MD 619-543-4755 dcroteau@ucsd.edu
United States
 
NCT01293123
11-0067
Yes
Scott Letendre, University of California, San Diego
University of California, San Diego
Merck Sharp & Dohme Corp.
Principal Investigator: Scott Letendre, MD University of California, San Diego
University of California, San Diego
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP