Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Raltegravir Cerebrospinal Fluid Pharmacodynamic Study in HIV-Infected Individuals

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: NCT01293123
Recruitment Status : Terminated (Did not meet enrollment goals)
First Posted : February 10, 2011
Results First Posted : October 31, 2019
Last Update Posted : October 31, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Scott Letendre, University of California, San Diego

Tracking Information
First Submitted Date  ICMJE February 9, 2011
First Posted Date  ICMJE February 10, 2011
Results First Submitted Date  ICMJE October 8, 2019
Results First Posted Date  ICMJE October 31, 2019
Last Update Posted Date October 31, 2019
Study Start Date  ICMJE December 2011
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 9, 2011)
Cerebrospinal Fluid HIV RNA Levels [ Time Frame: 180 days ]
Slope of decline of HIV RNA levels in CSF over time
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 9, 2011)
  • Neuropsychological Performance [ Time Frame: 180 days ]
    Change in neuropsychological performance over 180 days
  • Measure of Mood [ Time Frame: 180 days ]
    Change in mood over 180 days
  • Measure of Sleep [ Time Frame: 180 days ]
    Change in self-reported sleep performance over 180 days.
  • Measure of Quality of Life [ Time Frame: 180 days ]
    Change in self-report quality of life over 180 days
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Raltegravir Cerebrospinal Fluid Pharmacodynamic Study in HIV-Infected Individuals
Official Title  ICMJE Raltegravir Cerebrospinal Fluid Pharmacodynamic Study in HIV-Infected Individuals
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Raltegravir
    Intervention: Drug: Raltegravir
  • Active Comparator: Efavirenz
    Intervention: Drug: Efavirenz
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 8, 2019)
2
Original Estimated Enrollment  ICMJE
 (submitted: February 9, 2011)
15
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01293123
Other Study ID Numbers  ICMJE 11-0067
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Scott Letendre, University of California, San Diego
Study Sponsor  ICMJE University of California, San Diego
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Scott Letendre, MD University of California, San Diego
PRS Account University of California, San Diego
Verification Date October 2019

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