Investigation of Blood-Brain-Barrier Breakdown Using Manganese Magnetic Resonance Imaging in Drug-Resistant Epilepsy
| Status: | Recruiting |
|---|---|
| Conditions: | Neurology, Epilepsy |
| Therapuetic Areas: | Neurology, Other |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 3/8/2019 |
| Start Date: | August 22, 2015 |
| End Date: | June 28, 2019 |
| Contact: | Aaliyah H Thiam |
| Email: | aaliyah.hamidullahthiam@nih.gov |
| Phone: | (301) 496-5121 |
Background:
- The blood-brain barrier separates the brain from the rest of the body. Epilepsy is a
neurological disease that causes seizures. It can affect this barrier. Researchers think a
contrast agent called mangafodipir might be better able to show areas of the brain that
epilepsy affects.
Objective:
- To see if mangafodipir is well tolerated and safe. To see if it can show, on an MRI, areas
of the brain that epilepsy affects.
Eligibility:
- People ages 18-60 who:
- Have epilepsy not controlled by drugs
- Are enrolled in protocol 01-N-0139
Design:
- Participants will be screened with:
- Medical history
- Physical exam
- Blood and urine tests
- Participants will have up to 6 visits in 1 3 months. Those with epilepsy will have an
inpatient stay lasting 2 10 days. Visits may include:
- Video-EEG monitoring for participants with epilepsy (not for healthy volunteers)
- An IV catheter put in place: a needle guides a thin plastic tube into an arm vein.
- Getting mangafodipir through the IV.
- 5 MRI scans over a 10-day period: a magnetic field and radio waves take pictures of the
brain. Participants lie on a table that slides into a metal cylinder. They are in the
cylinder for 45 90 minutes, lying still for up to 10 minutes at a time. The scanner
makes loud knocking sounds. Participants will get earplugs.
- A final MRI at least 2 weeks after receiving mangafodipir. Gadolinium is given through
an IV catheter.
- The blood-brain barrier separates the brain from the rest of the body. Epilepsy is a
neurological disease that causes seizures. It can affect this barrier. Researchers think a
contrast agent called mangafodipir might be better able to show areas of the brain that
epilepsy affects.
Objective:
- To see if mangafodipir is well tolerated and safe. To see if it can show, on an MRI, areas
of the brain that epilepsy affects.
Eligibility:
- People ages 18-60 who:
- Have epilepsy not controlled by drugs
- Are enrolled in protocol 01-N-0139
Design:
- Participants will be screened with:
- Medical history
- Physical exam
- Blood and urine tests
- Participants will have up to 6 visits in 1 3 months. Those with epilepsy will have an
inpatient stay lasting 2 10 days. Visits may include:
- Video-EEG monitoring for participants with epilepsy (not for healthy volunteers)
- An IV catheter put in place: a needle guides a thin plastic tube into an arm vein.
- Getting mangafodipir through the IV.
- 5 MRI scans over a 10-day period: a magnetic field and radio waves take pictures of the
brain. Participants lie on a table that slides into a metal cylinder. They are in the
cylinder for 45 90 minutes, lying still for up to 10 minutes at a time. The scanner
makes loud knocking sounds. Participants will get earplugs.
- A final MRI at least 2 weeks after receiving mangafodipir. Gadolinium is given through
an IV catheter.
Objective: The primary goals of this pilot study is to (1) describe the safety profile of
administration of mangafodipir patients with epilepsy and (2) determine if peri-ictal
administration will allow focal entry of mangafodipir through the blood-brain-barrier and
manganese enhanced magnetic resonance imaging (MEMRI) visualization of seizure foci.
Secondary objectives are further exploration of MEMRI properties in patients with epilepsy.
Study population: 16 patients with drug-resistant epilepsy.
Design: Screening of enrolled participants will include a medical history, physical exam,
blood and urine laboratory testing. Patients will be imaged interictally with a gadolinium
enhanced MRI session. The administration of mangafodipir will be done as an inpatient during
long-term video EEG recording, to ensure administration in the peri-ictal period. Patients
will receive a baseline MRI scan, IV mangafodipir injection and will then be serially scanned
with non-contrast MRI scans.
Outcome measures: The primary outcomes are (1) description of the safety profile of
mangafodipir administration in patients with epilepsy, and (2) evaluation of the difference
between T1-weighted signal intensity in the brain measured after mangafodipir administration
in the seizure onset zone identified by standard clinical, EEG, and imaging studies, and the
homologous contralateral region.
administration of mangafodipir patients with epilepsy and (2) determine if peri-ictal
administration will allow focal entry of mangafodipir through the blood-brain-barrier and
manganese enhanced magnetic resonance imaging (MEMRI) visualization of seizure foci.
Secondary objectives are further exploration of MEMRI properties in patients with epilepsy.
Study population: 16 patients with drug-resistant epilepsy.
Design: Screening of enrolled participants will include a medical history, physical exam,
blood and urine laboratory testing. Patients will be imaged interictally with a gadolinium
enhanced MRI session. The administration of mangafodipir will be done as an inpatient during
long-term video EEG recording, to ensure administration in the peri-ictal period. Patients
will receive a baseline MRI scan, IV mangafodipir injection and will then be serially scanned
with non-contrast MRI scans.
Outcome measures: The primary outcomes are (1) description of the safety profile of
mangafodipir administration in patients with epilepsy, and (2) evaluation of the difference
between T1-weighted signal intensity in the brain measured after mangafodipir administration
in the seizure onset zone identified by standard clinical, EEG, and imaging studies, and the
homologous contralateral region.
- INCLUSION CRITERIA:
- Age 18-60
- Able to give written informed consent directly.
- Drug resistant epilepsy participants will be defined as having clinically documented
seizures with consistent EEG evidence as defined by the 1981 International
Classification of Epileptic Seizures, refractory to standard anti-seizure treatment
for at least one year prior to enrolling in this study and with an average of at least
one seizure per month. This criterion will be established by preliminary screening in
NINDS Clinical Epilepsy Service under protocol 18-N-0066. Seizure focus localization
will be determined by standard clinical, neurophysiologic, and imaging studies. Prior
or concurrent enrollment in 18-N-0066 is required.
EXCLUSION CRITERIA:
General exclusions:
- History of brain disease other than epilepsy.
- Patients with epilepsy who are not surgical candidates
- Positive test for HIV.
- History of post-ictal psychosis or post-ictal aggression
- 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.
-- Planning to get pregnant in the next 2 months
- Claustrophobia to a degree that the subject would feel uncomfortable in the MRI
machine.
- Cannot lie on their back for at least two hours.
- Risk for MRI scan, (e.g., any non-organic implant or other device such as a cardiac
pacemaker or infusion pump or other metallic implants, objects or body piercings that
cannot be removed, or history of being a welder or metal worker due to small metal
fragments in the eye)
- History of clinically significant medical disorders other than epilepsy, such as liver
or kidney disease, that could potentially increase the risk of CNS damage due to
manganese exposure
- A history of drug or alcohol abuse/dependence (subjects scoring 8 or higher on the
AUDIT scale)
- Screening lab abnormalities, demonstrating values outside of the range of normal for
AST, ALT, bilirubin, alkaline phosphatase, BUN, creatinine
- Previous presumed occupational exposure to manganese (i.e., having worked in a mine,
foundry, smelter, dry cell battery manufacturing facility, or agriculture)
- Allergy to manganese
- On-going treatment with calcium-channel blocker
- Iron-deficiency anemia
- Personal history of Parkinson s Disease or Parkinsonism or presence of this disease in
a 1st degree relative
- Unwilling to allow sharing and/or use in future studies of coded data that are
collected for this study
Gadolinium enhanced MRI component specific exclusions (not applicable for patients opting
out of this portion of the study):
- Estimated GFR greater than or equal to 60, tested within 1 week of scan
- Allergy to gadolinium
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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