Investigation of Blood-Brain-Barrier Breakdown Using Manganese Magnetic Resonance Imaging in Drug-Resistant Epilepsy

NCT02531880 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 15017715-N-0177
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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
• Prior or concurrent enrollment in 18-N-0066 is required 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
• 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....

Conditions

Epilepsy

Keywords

MRI; Manganese Enhanced MRI; Seizure Disorder; Seizures; Epileptic Focus

Outcome Measures

Primary Outcomes (2)

• evaluation of the utility of MEMRI and/or DCE-MRI in identifying focal BBBD in the seizure onset zone identified by standard clinical, EEG, and imaging studies, and the homologous contralateral region.

  evaluation of the utility of MEMRI and/or DCE-MRI in identifying focal BBBD in the seizure onset zone identified by standard clinical, EEG, and imaging studies, and the homologous contralateral region.

  after mangafodipir administration

• description of the safety profile of mangafodipir administration in patients with epilepsy

  safety profile

  after mangafodipir adminstration

Study Arms (1)

1

EXPERIMENTAL

Patients will be given the study drug

Drug: Mangafodipir

Interventions

Mangafodipir DRUG

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.

1

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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 NINDS 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.

You may not qualify if:

• Patients with epilepsy who are not surgical candidates
• Significant structural brain abnormality such as a brain tumor, stroke, brain damage from head trauma or blood vessel abnormalities, on the baseline MRI scan.
• Positive test for HIV
• Pregnancy or breast-feeding
• 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)
• Unwilling to allow sharing and/or use in future studies of coded data that are collected for this study
• History of post-ictal psychosis or post-ictal aggression
• Planning to get pregnant in the next 2 months
• History of clinically significant 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 more than 2 times the upper limit 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

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Epilepsy; Seizures

Interventions

N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Sara K Inati, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aaliyah M HamidullahThiam

CONTACT

(301) 402-7686; aaliyah.hamidullahthiam@nih.gov

Sara K Inati, M.D.

CONTACT

(301) 435-6269; inatisk@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2015
• First Posted: August 25, 2015
• Study Start: November 19, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-02-23

Locations

US (1)