Brain P-gp and Inflammation in People With Epilepsy
- The brain is protected by a barrier that keeps toxins in the blood from reaching the brain. However, this barrier can also keep useful medications from reaching the brain. P-glycoprotein (P-gp) is a brain protein that is part of the blood-brain barrier. The level of P-gp is higher in people with epilepsy than in people without epilepsy. These different levels of P-gp may explain why some people have seizures that do not respond well to medications. Researchers want to see if P-gp can affect the response to epilepsy medications.
- Epilepsy may also be associated with brain inflammation. Researchers also want to look at the part of the brain affected by epilepsy to see if inflammation is present.
- To see if P-gp can affect the response to epilepsy medications.
- To see if inflammation is present in the part of the brain affected by epilepsy.
- <TAB>Individuals between 18 and 60 years of age who have temporal lobe epilepsy. We plan to study some patients whose seizures are well controlled by drugs, and some whose seizures are not controlled.
- Healthy volunteers between 18 and 60 years of age.
- This study requires four or five visits to the NIH Clinical Center over the course of a year. The visits will be outpatient visits and will last from 2 to 5 hours.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
- All participants will have two positron emission tomography (PET) scans. The scans will take place during different visits. Different drugs will be used in each scan. One drug will be used to temporarily block the effect of P-gp in the brain. The other drug will show areas of inflammation in the brain.
- Participants with epilepsy will have a third PET scan. This scan will also look at P-gp activity in the brain. However, it will not use the drug that blocks the effect of P-gp.
- All participants will also have one magnetic resonance imaging scan. This scan will help show brain function.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Positron Emission Tomography Measurement of Neuroinflammation in Focal Epilepsy|
- Amount of differential [11C]dLop and [11C]PBR28 uptake between the epileptic focus and the homologous contralateral region [ Time Frame: study completion ]
- Secondary Outcome Measure: A secondary goal is to determine if inhibiting P-gp with tariquidar results in increased concentrations of anti-epileptic medications into the CSF, as a surrogate marker for increased penetration of these medication... [ Time Frame: study completion ]
|Study Start Date:||July 31, 2012|
- To study the role of inflammation in focal epilepsy
- To characterize the BBB state in patients with focal epilepsy using MRI, and compare the results with PET imaging of inflammation
- To study test-retest replicability of [11C]PBR28 PET scanning.
50 participants with drug-resistant focal epilepsy, 25 participants with drug-responsive focal epilepsy and 25 healthy volunteers.
Screening of enrolled participants will include a medical history, physical exam, electrocardiogram (ECG), and blood and urine laboratory testing. Blood samples will also be used for genetic polymorphism study. Healthy volunteers will receive one or two brain positron emission tomography (PET) scans with [11C]PBR28. Epilepsy participants will receive one or two PET scans with [11C]PBR28). Everyone will receive a brain magnetic resonance imaging (MRI). Some participants will also have a second MRI with gadolinium infusion to measure blood-brain barrier permeability.
The primary outcome measure will be the amount of differential [11C]PBR28 uptake between the epileptic focus and the homologous contralateral region. [11C]PBR28 distribution volume (VT) will be measured using an arterial input function. We want to quantify the tracer VT in regions of the brain distant from the epileptic focus, which may be affected by the disease.
We hypothesize that focal epilepsy will be associated with brain inflammation and, therefore, that [11C]PBR28 uptake in the affected side of the brain will be higher than in the contralateral side.
We will study the polymorphism of the translocator protein (TSPO), because TSPO polymorphism has an influence on [11C]PBR28 binding. This polymorphism is due to the non-conservative amino-acid substitution at position 147 from alanine to threonine (Ala147Thr) in the fifth transmembrane domain of the TSPO protein.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01663545
|Contact: Tamika Mason||(301) firstname.lastname@example.org|
|Contact: William H Theodore, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||William H Theodore, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|