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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 : Recruiting
First Posted : August 25, 2015
Last Update Posted : July 12, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Epilepsy Drug: Mangafodipir Phase 1

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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 : August 31, 2021
Estimated Study Completion Date : August 31, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Manganese

Arm Intervention/treatment
Experimental: 1
Patients will be given the study drug
Drug: Mangafodipir
A contrast agent previously approved for liver imaging with MRI, which contains manganese.




Primary Outcome Measures :
  1. description of the safety profiIe of mangafodipir administration in patients with epiIepsy [ Time Frame: after mangafodipir administration ]
    safety profile

  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 regio... [ Time Frame: after mangafodipir administration ]
    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.


Secondary Outcome Measures :
  1. MEMRI Comparison of MEMRI localization with standard presurgical localization. [ Time Frame: ongoing ]
    MEMRI

  2. DSC/DCE MRI-Permeability parameters (Ktrans, K2) in homologous brain regions. [ Time Frame: ongoing ]
    DSC/DCE MRI

  3. DSC/DCE MRI Comparison between permeability measures and presurgical localization. [ Time Frame: ongoing ]
    DSC/DCE MRI

  4. MEMRI-Spatiotemporal evolution of enhancement over scans at baseline and days 0-35. [ Time Frame: baseline, days 0-35 ]
    MEMR



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • 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

Information from the National Library of Medicine

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


Contacts
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Contact: Aaliyah H Hamidullah-Thiam (301) 496-5121 aaliyah.hamidullahthiam@nih.gov

Locations
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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 Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Sara K Inati, M.D. National Institute of Neurological Disorders and Stroke (NINDS)

Additional Information:
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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT02531880     History of Changes
Other Study ID Numbers: 150177
15-N-0177
First Posted: August 25, 2015    Key Record Dates
Last Update Posted: July 12, 2019
Last Verified: July 8, 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
MRI
Manganese Enhanced MRI
Seizure Disorder
Seizures
Epileptic Focus

Additional relevant MeSH terms:
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Epilepsy
Drug Resistant Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Manganese
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs