Investigation of Blood-Brain-Barrier Breakdown Using Manganese Magnetic Resonance Imaging in Drug-Resistant Epilepsy
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|ClinicalTrials.gov Identifier: NCT02531880|
Recruitment Status : Suspended
First Posted : August 25, 2015
Last Update Posted : March 29, 2018
- 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.
- 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.
- People ages 18-60 who:
- Have epilepsy not controlled by drugs
- Are enrolled in protocol 01-N-0139
- Healthy volunteers
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Epilepsy||Drug: Mangafodipir||Phase 1|
Objective: The primary goals of this pilot study is to determine if (1) administration of mangafodipir is well tolerated by healthy volunteers and patients with epilepsy and if (2) 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 and comparison with healthy volunteers.
Study population: 16 patients with drug-resistant epilepsy, and up to 16 healthy controls.
Design: Screening of enrolled participants will include a medical history, physical exam, blood and urine laboratory testing. Patients and healthy volunteers will be imaged interictally with a gadolinium enhanced MRI session. For patients, 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 and controls 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) clinical safety parameters of mangafodipir administration, and (2) 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Investigation of Blood-Brain-Barrier Breakdown Using Manganese Magnetic Resonance Imaging in Drug-Resistant Epilepsy|
|Study Start Date :||August 22, 2015|
|Estimated Primary Completion Date :||June 30, 2018|
|Estimated Study Completion Date :||June 28, 2019|
- The laterality index, measuring the difference between normalized T1-weighted signal intensity, between the clinically defined epileptogenic zone and the contralateral homologous region. [ Time Frame: 10 days ]
- Subjects will be clinically monitored during and after administration of mangafodipir for adverse events. Patients will have close neurological monitoring in the first 24 hours as well. [ Time Frame: 10 days ]
- MEMRI b) Comparison of MEMRI localization with standard presurgical localization. [ Time Frame: 10 days ]
- MEMRI c) Difference in enhancement patterns between healthy volunteers and people with epilepsy. [ Time Frame: 10 days ]
- DCE/DSC - a) Permeability parameters (Ktrans, K2) in homologous brain regions. [ Time Frame: 1 day ]
- DCE/DSC - b) Comparison between permeability measures and presurgical localization. [ Time Frame: 1 day ]
- DCE/DSC - c) Difference in permeability patterns between healthy volunteers and people with epilepsy. [ Time Frame: 1 day ]
- MEMRI a) Spatiotemporal evolution of enhancement over scans at baseline and days 0-10. [ Time Frame: 10 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02531880
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Daniel M Goldenholz, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|