Epilepsies, PartialNCT01663545
Brain P-gp and Inflammation in People With Epilepsy
An observational study of Epilepsies, Partial, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Epilepsies, Partial
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jul 2012to 4 Oct 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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 2010 Revised terminology and concepts for organization of seizures and epilepsies and refractory to standard antiepileptic treatment for at least one year 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.
- Drug-responsive participants will be defined as having clinically documented partial seizures with consistent EEG evidence as defined by the 2010 Revised terminology and concepts for organization of seizures and epilepsies, seizure-free on 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.
- No prior diagnosis of drug or alcohol abuse or dependence.
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- For healthy volunteers
- Age 18-60.
- Able to give written informed consent.
- No prior diagnosis of drug or alcohol abuse or dependence.
Who cannot join
- For patients
- Previous research radiation exposure (X-rays, PET scans etc.) that, together with study procedures, would exceed the NIH RSC 5 rad per year research limit.
- 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.
- Serious medical illness, other than epilepsy.
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- Clinically significant laboratory abnormalities.
- Brain abnormality such as a brain tumor, infection, 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.
- NIH employee or staff member
- For healthy volunteers
- Clinically significant laboratory abnormalities.
- 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.
- Previous research radiation exposure (X-rays, PET scans etc.) that, together with study procedures, would exceed the NIH RSC 5 rad per year research limit.
- Inability to lie flat on camera bed for at least two hours.
- PBR28 non-binders
- Pregnancy or breast feeding.
- Able to get pregnant but does not use birth control.
- NIH employee or staff member
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Positron Emission Tomography Measurement of Neuroinflammation in Focal Epilepsy
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.
Read more
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.
Read the detailed description
Objectives:
- 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.
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.
- Conditions
- Epilepsies, Partial
- Keywords
- Epilepsy, Epileptic Focus, Inflammation, P-Glycoprotein, PET Imaging
- Medical subject headings
- Epilepsies, Partial, Epilepsy, Inflammation
What is being measured
The primary outcome is the main question the study is designed to answer.
Amount of differential [11C]dLop and [11C]PBR28 uptake between the epileptic focus and the homologous contralateral region
Measured: study completion
Secondary outcomes (1)
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...
Measured: study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2012 (estimated)
- Study start31 Jul 2012
- Study completion4 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Epilepsies, PartialStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- William H Theodore, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01663545
- Sponsor's protocol ID
- 120182
- Other IDs
- 12-N-0182
- Status last verified
- 4 Oct 2017
- First submitted
- 8 Aug 2012
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Aronica E, Gorter JA, Redeker S, van Vliet EA, Ramkema M, Scheffer GL, Scheper RJ, van der Valk P, Leenstra S, Baayen JC, Spliet WG, Troost D. Localization of breast cancer resistance protein (BCRP) in microvessel endothelium of human control and epileptic brain. Epilepsia. 2005 Jun;46(6):849-57. doi: 10.1111/j.1528-1167.2005.66604.x.
PubMed 15946326Aronica E, Boer K, van Vliet EA, Redeker S, Baayen JC, Spliet WG, van Rijen PC, Troost D, da Silva FH, Wadman WJ, Gorter JA. Complement activation in experimental and human temporal lobe epilepsy. Neurobiol Dis. 2007 Jun;26(3):497-511. doi: 10.1016/j.nbd.2007.01.015. Epub 2007 Feb 20.
PubMed 17412602Boer K, Troost D, Spliet WG, van Rijen PC, Gorter JA, Aronica E. Cellular distribution of vascular endothelial growth factor A (VEGFA) and B (VEGFB) and VEGF receptors 1 and 2 in focal cortical dysplasia type IIB. Acta Neuropathol. 2008 Jun;115(6):683-96. doi: 10.1007/s00401-008-0354-6. Epub 2008 Mar 4.
PubMed 18317782
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Positron Emission Tomography Measurement of Neuroinflammation in Focal Epilepsy
- ClinicalTrials.gov ID
- NCT01663545
- Acronym / sponsor ID
- 120182
- Conditions
- Epilepsies, Partial
- Keywords
- Epilepsy, Epileptic Focus, Inflammation, P-Glycoprotein, PET Imaging
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 31 Jul 2012
- Study completion
- 4 Oct 2017
- First posted
- 13 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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 2010 Revised terminology and concepts for organization of seizures and epilepsies and refractory to standard antiepileptic treatment for at least one year 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.
- Drug-responsive participants will be defined as having clinically documented partial seizures with consistent EEG evidence as defined by the 2010 Revised terminology and concepts for organization of seizures and epilepsies, seizure-free on 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.
Key exclusion criteria (25 listed)
- For patients
- Previous research radiation exposure (X-rays, PET scans etc.) that, together with study procedures, would exceed the NIH RSC 5 rad per year research limit.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Amount of differential [11C]dLop and [11C]PBR28 uptake between the epileptic focus and the homologous contralateral region
Time frame: study completion
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Background: PubMed 15946326Aronica E, Gorter JA, Redeker S, van Vliet EA, Ramkema M, Scheffer GL, Scheper RJ, van der Valk P, Leenstra S, Baayen JC, Spliet WG, Troost D. Localization of breast cancer resistance protein (BCRP) in microvessel endothelium of human control and epileptic brain. Epilepsia. 2005 Jun;46(6):849-57. doi: 10.1111/j.1528-1167.2005.66604.x.
- Background: PubMed 17412602Aronica E, Boer K, van Vliet EA, Redeker S, Baayen JC, Spliet WG, van Rijen PC, Troost D, da Silva FH, Wadman WJ, Gorter JA. Complement activation in experimental and human temporal lobe epilepsy. Neurobiol Dis. 2007 Jun;26(3):497-511. doi: 10.1016/j.nbd.2007.01.015. Epub 2007 Feb 20.
- Background: PubMed 18317782Boer K, Troost D, Spliet WG, van Rijen PC, Gorter JA, Aronica E. Cellular distribution of vascular endothelial growth factor A (VEGFA) and B (VEGFB) and VEGF receptors 1 and 2 in focal cortical dysplasia type IIB. Acta Neuropathol. 2008 Jun;115(6):683-96. doi: 10.1007/s00401-008-0354-6. Epub 2008 Mar 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William H Theodore, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Epilepsies, Partial, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amount of differential [11C]dLop and [11C]PBR28 uptake between the epileptic focus and the homologous contralateral region (time frame: study completion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01663545, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2018.