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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. 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
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Scott Letendre, University of California, San Diego

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.

Condition or disease Intervention/treatment Phase
HIV Drug: Raltegravir Drug: Efavirenz Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Raltegravir Cerebrospinal Fluid Pharmacodynamic Study in HIV-Infected Individuals
Study Start Date : December 2011
Actual Primary Completion Date : June 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Cerebrospinal Fluid HIV RNA Levels [ Time Frame: 180 days ]
    Slope of decline of HIV RNA levels in CSF over time

Secondary Outcome Measures :
  1. Neuropsychological Performance [ Time Frame: 180 days ]
    Change in neuropsychological performance over 180 days

  2. Measure of Mood [ Time Frame: 180 days ]
    Change in mood over 180 days

  3. Measure of Sleep [ Time Frame: 180 days ]
    Change in self-reported sleep performance over 180 days.

  4. Measure of Quality of Life [ Time Frame: 180 days ]
    Change in self-report quality of life over 180 days

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01293123

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United States, California
UCSD Antiviral Research Center
San Diego, California, United States, 92103
Sponsors and Collaborators
University of California, San Diego
Merck Sharp & Dohme Corp.
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Principal Investigator: Scott Letendre, MD University of California, San Diego
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Responsible Party: Scott Letendre, Associate Professor of Medicine, University of California, San Diego Identifier: NCT01293123    
Other Study ID Numbers: 11-0067
First Posted: February 10, 2011    Key Record Dates
Results First Posted: October 31, 2019
Last Update Posted: October 31, 2019
Last Verified: October 2019
Keywords provided by Scott Letendre, University of California, San Diego:
cerebrospinal fluid
Additional relevant MeSH terms:
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Raltegravir Potassium
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers
HIV Integrase Inhibitors
Integrase Inhibitors