Brain P-gp and Inflammation in People With Epilepsy
Condition: Epilepsies, Partial
MeSH terms: Epilepsy; Epilepsies, Partial
Study type: Observational

Summary: 
      Background:

        -  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.

      Objectives:

        -  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.

      Eligibility:

        -  <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.

        -  <TAB>

        -  Healthy volunteers between 18 and 60 years of age.

      Design:

        -  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.
    

Detailed description: 
      Objectives:

        1. To study the role of inflammation in focal epilepsy

        2. To characterize the BBB state in patients with focal epilepsy using MRI, and compare the
           results with PET imaging of inflammation

        3. To study test-retest replicability of [11C]PBR28 PET scanning.

      Study population:

      50 participants with drug-resistant focal epilepsy, 25 participants with drug-responsive
      focal epilepsy and 25 healthy volunteers.

      Design:

      Screening of enrolled participants will include a medical history, physical exam, 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.

      Outcome measures:

      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.
    

Observational model: Cohort
Time perspective: Prospective
Keywords: Epilepsy; Epileptic Focus; Inflammation; P-Glycoprotein; PET Imaging