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

Primary Purpose

Epilepsy

Status

Not yet recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Mangafodipir

About this trial

This is an interventional diagnostic trial for Epilepsy focused on measuring MRI, Manganese Enhanced MRI, Seizure Disorder, Seizures, Epileptic Focus

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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:

Patients with epilepsy who are not surgical candidates
Positive test for HIV.
History of post-ictal psychosis or post-ictal aggression
Significant structural brain abnormality such as a brain tumor, stroke, brain damage from head trauma or blood vessel abnormalities, on the baseline 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 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
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 < 60, tested within 1 week of scan
Allergy to gadolinium

Sites / Locations

National Institutes of Health Clinical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

Patients will be given the study drug

Outcomes

Primary Outcome Measures

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...

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

safety profile

Secondary Outcome Measures

Full Information

NCT ID

NCT02531880

First Posted

August 22, 2015

Last Updated

October 18, 2023

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

1. Study Identification

Unique Protocol Identification Number

NCT02531880

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 20, 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

November 6, 2023 (Anticipated)

Primary Completion Date

April 1, 2024 (Anticipated)

Study Completion Date

August 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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....

Detailed Description

Objective: The primary goals of this pilot study is to (1) describe the safety profile of administration of mangafodipir in 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 periictal 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epilepsy

Keywords

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

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Patients will be given the study drug

Intervention Type

Drug

Intervention Name(s)

Mangafodipir

Intervention Description

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.

Primary Outcome Measure Information:

Title

Description

Time Frame

after mangafodipir administration

Title

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

Description

safety profile

Time Frame

after mangafodipir adminstration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility 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: Patients with epilepsy who are not surgical candidates Positive test for HIV. History of post-ictal psychosis or post-ictal aggression Significant structural brain abnormality such as a brain tumor, stroke, brain damage from head trauma or blood vessel abnormalities, on the baseline 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 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 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 < 60, tested within 1 week of scan Allergy to gadolinium

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Aaliyah H Hamidullah-Thiam

Phone

(301) 402-7686

aaliyah.hamidullahthiam@nih.gov

First Name & Middle Initial & Last Name or Official Title & Degree

Sara K Inati, M.D.

Phone

(301) 435-6269

inatisk@mail.nih.gov

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sara K Inati, M.D.

Organizational Affiliation

National Institute of Neurological Disorders and Stroke (NINDS)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Phone

800-411-1222

Ext

TTY dial 711

ccopr@nih.gov

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Links:

URL

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2015-N-0177.html

Description

NIH Clinical Center Detailed Web Page

Learn more about this trial

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

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