EpilepsyPhase 1NCT02531880
Investigation of Blood-Brain-Barrier Breakdown Using Manganese Magnetic Resonance Imaging in Drug-Resistant Epilepsy
A Phase 1 study testing Mangafodipir and Gadolinium in people with Epilepsy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Epilepsy
- What is being tested?
- Mangafodipir and Gadolinium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Nov 2024to 1 Jul 2030
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- General exclusions:
- 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.
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- 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
- MEMRI component specific exclusions (applicable only to patients participating in this arm of the 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
- 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
- Gadolinium enhanced MRI component specific exclusions (applicable only to patients participating in this arm of the study):
- Estimated GFR <60, tested within 1 week of scan
- Allergy to gadolinium
- Of note, patients who are ineligible for one arm of the study may still be eligible for and participate in the other arm of the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
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.
Read more
Objective:
- To see if mangafodipir is well tolerated and safe. To see if magnetic resonance imaging (MRI) using either mangafodipir or gadolinium can show areas of blood-brain barrier breakdown in people with epilepsy.
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. One visit is 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.
- Getting gadolinium through the IV.
- Up to 6 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....
Read the detailed description
Objective:
The primary goals of this pilot study are to (1) describe the safety profile of administration of mangafodipir in patients with epilepsy and (2) investigate the prevalence of blood-brain barrier disruption (BBBD) in patients with drug-resistant focal epilepsy using peri-ictal manganese enhanced magnetic resonance imaging (MEMRI) and interictal gadolinium dynamic contrast-enhanced MRI (DCE-MRI) and determine if these methods will allow for visualization of seizure foci. Secondary objectives are further exploration of MEMRI and DCE-MRI properties in patients with epilepsy.
Study population:
40 patients with drug-resistant epilepsy.
Design:
Screening of enrolled participants will include a medical history, physical exam, blood and urine laboratory testing. There are two arms of this study; patients may be enrolled in either arm or both. For one arm, patients will be imaged interictally with a gadolinium enhanced MRI session (DCE-MRI). For the other arm, patients will be imaged peri-ictally with manganese enhanced MRI (MEMRI) 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 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.
- Conditions
- Epilepsy
- Being tested
- Mangafodipir, Gadolinium
- Keywords
- MRI, Manganese Enhanced MRI, Seizure Disorder, Seizures, Epileptic Focus
- Medical subject headings
- Epilepsy, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MangafodipirDrug
Patients will be imaged interictally with the administration of mangafodipir as an inpatient during long-term video EEG recording, to ensure administration in the peri-ictal period.
GadoliniumDrug
Patients will be imaged with a gadolinium enhanced MRI session.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Patients will be given the manganese contrast before 3T MRI. Receives: Drug: Mangafodipir |
| 2 | Experimental | Patients will be given gadolinium contrast before 7T MRI. Receives: Drug: Gadolinium |
What is being measured
The primary outcome is the main question the study is designed to answer.
description of the safety profile of mangafodipir administration in patients with epilepsy
safety profile
Measured: after mangafodipir adminstration
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.
Measured: after mangafodipir and/or gadolinium administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2015 (estimated)
- Study start19 Nov 2024
- Primary completion1 Jul 2030 (estimated)
- Study completion1 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sara K Inati, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02531880
- Sponsor's protocol ID
- 150177
- Other IDs
- 15-N-0177
- Status last verified
- 4 Jun 2026
- First submitted
- 22 Aug 2015
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided