Brain P-gp and Inflammation in People With Epilepsy

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01663545
First received: August 8, 2012
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

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.

Condition
Epilepsies, Partial

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Positron Emission Tomography Measurement of Neuroinflammation and P-glycoprotein in Localization-Related Epilepsy

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 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 medications into the central nervous sys...

Estimated Enrollment: 75
Study Start Date: July 2012
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

For patients

  • Age 18-60.
  • Able to give written informed consent.
  • Drug resistant participants will be defined as having clinically documented partial seizures with consistent EEG evidence as defined by the 1981 International Classification of Epileptic Seizures, refractory to standard antiepileptic treatment for at least one year prior to enrolling in this study and with an average of at least one seizure per week. This criterion will be established by preliminary screening in the NINDS Clinical Epilepsy Section outpatient clinic under protocol 01-N-0139, and if necessary, inpatient video-EEG monitoring. Seizure focus localization will be determined by standard clinical, neurophysiologic, and imaging studies.
  • Drug-responsive participants will be defined as having clinically documented partial seizures with consistent EEG evidence as defined by the 1981 International Classification of Epileptic Seizures, responsive to standard antiepileptic treatment for at least three months prior to enrolling in this study. This criterion will be established by preliminary screening in the NINDS Clinical Epilepsy Section outpatient clinic under protocol 01-N-0139, and if necessary, inpatient video-EEG monitoring. Seizure focus localization will be determined by standard clinical, neurophysiologic, and imaging studies.
  • Negative toxicology testing at the time of screening.
  • No prior diagnosis of drug or alcohol abuse or dependence.

For healthy volunteers

  • Age 18-60.
  • Able to give written informed consent.
  • No prior diagnosis of drug or alcohol abuse or dependence.rom the blood.

EXCLUSION CRITERIA:

For patients

  • Previous radiation exposure (X-rays, PET scans etc.) that, together with study procedures, would exceed NIH RSC research limits.
  • Claustrophobia to a degree that the subject would feel uncomfortable in the MRI machine.
  • History of brain disease other than epilepsy.
  • Cannot lie on their back for at least two hours.
  • Use of medications that may interfere with P-gp function in the 16 days before Tariquidar administration, except clinically needed antiepileptic drugs. For reference we have included a list of medications that may interfere with P-gp function. Drugs should be avoided for a period of 16 days before Tariquidar to one week after.
  • Known cause for seizures, other than mesial temporal sclerosis, such as tumor or infection.
  • Serious medical illness, other than epilepsy.
  • Clinically significant laboratory abnormalities.
  • Positive test for HIV.
  • Brain abnormality such as a brain tumor, stroke, brain damage from head trauma or blood vessel abnormalities, on an MRI scan.
  • Pregnancy or breast feeding.
  • Able to get pregnant but does not use birth control.
  • Risk for MRI scan, such as a pacemaker or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or shrapnel fragments. Welders and metal workers are also at risk for injury because of possible small metal fragments in the eye of which they may be unaware.
  • PBR28 non-binders.
  • For drug-responsive subjects: occurrence of a seizure within the last three months.

For healthy volunteers

  • Any current Axis I diagnosis.
  • Clinically significant laboratory abnormalities.
  • Positive test for HIV.
  • Unable to have a MRI Scan.
  • History of neurologic illness or injury with the potential to affect study data interpretation.
  • History of seizures, other than in childhood and related to fever.
  • Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.
  • Inability to lie flat on camera bed for at least two hours.
  • Use of medications that interfere with P-gp function in the two weeks before Tariquidar administration. For reference we have included a list of medications that may interfere with P-gp function. Drugs should be avoided for a period of two weeks before Tariquidar to one week after.
  • PBR28 non-binders
  • Pregnancy or breast feeding.
  • Able to get pregnant but does not use birth control.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01663545

Contacts
Contact: Patricia M Reeves-Tyer, R. EEG T. (301) 496-1923 tyerp@ninds.nih.gov
Contact: William H Theodore, M.D. (301) 496-1505 theodorw@ninds.nih.gov

Locations
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    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: William H Theodore, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01663545     History of Changes
Other Study ID Numbers: 120182, 12-N-0182
Study First Received: August 8, 2012
Last Updated: March 25, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Epilepsy
Epileptic Focus
Inflammation
P-Glycoprotein
PET Imaging

Additional relevant MeSH terms:
Epilepsy
Epilepsies, Partial
Inflammation
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on September 11, 2014