Raltegravir Cerebrospinal Fluid Pharmacodynamic Study in HIV-Infected Individuals

HIV Clinical Trial

Official title:

Raltegravir Cerebrospinal Fluid Pharmacodynamic Study in HIV-Infected Individuals

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01293123
• Other study ID #: 11-0067
• Status: Terminated
• Phase: N/A
• Start date: December 2011
• Est. completion date: December 2013

Study information

• Verified date: October 2019
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: December 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Raltegravir
raltegravir 400 mg PO twice daily
• Efavirenz
efavirenz 600 mg PO once daily

Locations

Country	Name	City	State
United States	UCSD Antiviral Research Center	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Diego	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cerebrospinal Fluid HIV RNA Levels	Slope of decline of HIV RNA levels in CSF over time	180 days
Secondary	Neuropsychological Performance	Change in neuropsychological performance over 180 days	180 days
Secondary	Measure of Mood	Change in mood over 180 days	180 days
Secondary	Measure of Sleep	Change in self-reported sleep performance over 180 days.	180 days
Secondary	Measure of Quality of Life	Change in self-report quality of life over 180 days	180 days