Mild Neurocognitive Disorder in HIV Infection of the Brain
|ClinicalTrials.gov Identifier: NCT01547754|
Recruitment Status : Terminated
First Posted : March 8, 2012
Last Update Posted : July 2, 2017
- Some people with human immunodeficiency virus (HIV) develop problems with thinking and concentration when the virus affects the brain. This is known as mild neurocognitive disorder (MND). Research has shown that some HIV medications do not get through the blood brain barrier very well. P-glycoprotein (P-gp) is a brain protein that is part of the blood brain barrier. Differences in the activity of P-gp may help explain why some people with HIV develop MND. It is also possible that MND is partly due to inflammation in the brain. Researchers want to study P-gp and its effect on MND and HIV infection.
- To study P-gp and brain inflammation related to HIV infection.
- Individuals between 18 and 60 years of age who have HIV and either do or do not have MND.
- Healthy volunteers between 18 and 60 years of age.
- Participants will be screened with a medical history and physical exam. Blood and urine samples will be collected.
- Participants will have one outpatient visit and one 3-day inpatient stay.
- At the outpatient visit, participants will provide blood samples and have a lumbar puncture (spinal tap). The spinal tap will collect cerebrospinal fluid for study.
- At the inpatient visit, participants will have two positron emission tomography (PET) scans of the brain. These scans will study brain activity and possible inflammation. One scan will involve a study drug called tariquidar, which blocks the activity of P-gp. A second lumbar puncture will be done before the first PET scan. Blood and urine samples will be collected daily.
|Condition or disease|
|HIV-Associated Cognitive Motor Complex|
To determine the relationship among neuroinflammation, Permeability-glycoprotein (P-gp) function and mild neurocognitive disorder (MND), a cognitive disorder associated with HIV infection.
HIV seropositive subjects with MND, HIV seropositive subjects with normal cognitive function, and HIV seronegative control subjects.
Subjects will undergo history and physical exam, screening laboratory tests, EKG, brain MRI and neuropsychological evaluation. HIV-seropositive subjects will be stratified based on results of neuropsychological evaluation into HIV-seropositive controls (i.e., cognitively normal) and HIV-seropositive with MND. All subjects will receive brain PET imaging with [11C]dLop after P-gp blockade to measure the function of P-gp at the blood-brain barrier. P-gp will be blocked prior to the PET scan with tariquidar. HIV-seropositive subjects will receive one lumbar puncture at baseline and one lumbar puncture after P-gp blockade with tariquidar to measure CSF concentrations of anti-retroviral medications and to measure biomarkers of blood-brain barrier integrity and inflammation in the CSF. HIV-seronegative subjects will receive one lumbar puncture at baseline to measure biomarkers of blood-brain barrier integrity and inflammation in the CSF.
The main outcome measures of the study is brain uptake of [11C]dLop in response to P-gp blockade with tariquidar. We will correct for individual metabolism of tariquidar by measuring the plasma concentration of tariquidar during the P-gp blocked scan.
As a secondary outcome measure, concentrations of anti-retroviral medications in CSF will be measured in HIV seropositive subjects with and without MND. CSF concentrations will be used as a surrogate marker for CNS delivery of anti-retroviral drugs.
|Study Type :||Observational|
|Actual Enrollment :||8 participants|
|Official Title:||Inflammation and Function of P-gp in HIV Infection of Brain|
|Study Start Date :||January 9, 2012|
|Estimated Study Completion Date :||August 25, 2014|
- Brain uptake of [11C]dLop after pharmacological challenge with the P-gp inhibitor tariquidar.
- Cerebrospinal fluid concentrations of antiretroviral drugs and inflammatory markers.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01547754
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Robert B Innis, M.D.||National Institute of Mental Health (NIMH)|