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Trial record 8 of 146 for:    epilepsy AND Bethesda

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 : November 8, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Tracking Information
First Submitted Date  ICMJE August 22, 2015
First Posted Date  ICMJE August 25, 2015
Last Update Posted Date November 8, 2019
Study Start Date  ICMJE August 22, 2015
Estimated Primary Completion Date August 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2019)
  • description of the safety profiIe of mangafodipir administration in patients with epiIepsy [ Time Frame: after mangafodipir administration ]
    safety profile
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 22, 2015)
  • 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 ]
Change History Complete list of historical versions of study NCT02531880 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2019)
  • MEMRI Comparison of MEMRI localization with standard presurgical localization. [ Time Frame: ongoing ]
    MEMRI
  • DSC/DCE MRI-Permeability parameters (Ktrans, K2) in homologous brain regions. [ Time Frame: ongoing ]
    DSC/DCE MRI
  • DSC/DCE MRI Comparison between permeability measures and presurgical localization. [ Time Frame: ongoing ]
    DSC/DCE MRI
  • MEMRI-Spatiotemporal evolution of enhancement over scans at baseline and days 0-35. [ Time Frame: baseline, days 0-35 ]
    MEMR
Original Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2015)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Investigation of Blood-Brain-Barrier Breakdown Using Manganese Magnetic Resonance Imaging in Drug-Resistant Epilepsy
Official Title  ICMJE Investigation of Blood-Brain-Barrier Breakdown Using Manganese Magnetic Resonance Imaging in Drug-Resistant Epilepsy
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Epilepsy
Intervention  ICMJE Drug: Mangafodipir
A contrast agent previously approved for liver imaging with MRI, which contains manganese.
Study Arms  ICMJE Experimental: 1
Patients will be given the study drug
Intervention: Drug: Mangafodipir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 9, 2019)
20
Original Estimated Enrollment  ICMJE
 (submitted: August 22, 2015)
40
Estimated Study Completion Date  ICMJE August 31, 2021
Estimated Primary Completion Date August 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Aaliyah H Hamidullah-Thiam (301) 496-5121 aaliyah.hamidullahthiam@nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02531880
Other Study ID Numbers  ICMJE 150177
15-N-0177
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
Study Sponsor  ICMJE National Institute of Neurological Disorders and Stroke (NINDS)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Sara K Inati, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date July 8, 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP