Mild Neurocognitive Disorder in HIV Infection of the Brain
|First Received Date ICMJE||March 6, 2012|
|Last Updated Date||December 13, 2013|
|Start Date ICMJE||January 2012|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Brain uptake of [11C]dLop after pharmacological challenge with the P-gp inhibitor tariquidar; brain uptake of [11C]PBR28.|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01547754 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Cerebrospinal fluid concentrations of antiretroviral drugs and inflammatory markers.|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Mild Neurocognitive Disorder in HIV Infection of the Brain|
|Official Title ICMJE||Inflammation and Function of P-gp in HIV Infection of Brain|
- 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.
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. Subjects will also receive brain PET imaging with [11C]PBR28 to measure neuroinflammation. 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 are: 1) 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, and 2) brain uptake of [11C]PBR28.
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 ICMJE||Observational|
|Study Design ICMJE||Time Perspective: Prospective|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition ICMJE||HIV-Associated Cognitive Motor Complex|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||95|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Specific inclusion criteria for mild neurocognitive disorder are as follows:
Note: The rationale for the exclusion criteria for alcohol use is to avoid alcohol-related cognitive impairment as a confounding factor.
|Ages||18 Years to 60 Years|
|Accepts Healthy Volunteers||Yes|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01547754|
|Other Study ID Numbers ICMJE||120059, 12-M-0059|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Mental Health (NIMH)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||June 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP