Manganese-Enhanced Magnetic Resonance Imaging in Healthy Volunteers and People With Multiple Sclerosis
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Neurology, Ocular, Multiple Sclerosis |
| Therapuetic Areas: | Neurology, Ophthalmology, Other |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 4/6/2019 |
| Start Date: | March 30, 2011 |
| End Date: | June 1, 2021 |
Background:
- Contrast agents are drugs that make certain body areas or abnormalities show up better on
imaging studies, such as magnetic resonance imaging (MRI) scans. Mangafodipir is an MRI
contrast agent with manganese that has been approved for MRI scans of the liver and pancreas.
Because contrast agents with manganese have also been shown to be useful in studying problems
with the nervous system, researchers are interested in determining if mangafodipir may be
used for MRI scans of the brain or eye, two areas that often experience problems caused by
disorders that affect the nervous system, such as multiple sclerosis. However, more
information is needed on whether mangafodipir will be useful for this purpose, or how best to
use it in MRI scans of the eye and brain. To study mangafodipir more closely, researchers are
interested in studying its use in both individuals with multiple sclerosis and healthy
volunteers.
Background:
- Contrast agents are drugs that make certain body areas or abnormalities show up better on
imaging studies, such as magnetic resonance imaging (MRI) scans. Mangafodipir is an MRI
contrast agent with manganese that has been approved for MRI scans of the liver and pancreas.
Because contrast agents with manganese have also been shown to be useful in studying problems
with the nervous system, researchers are interested in determining if mangafodipir may be
used for MRI scans of the brain or eye, two areas that often experience problems caused by
disorders that affect the nervous system, such as multiple sclerosis. However, more
information is needed on whether mangafodipir will be useful for this purpose, or how best to
use it in MRI scans of the eye and brain. To study mangafodipir more closely, researchers are
interested in studying its use in both individuals with multiple sclerosis and healthy
volunteers.
Objectives:
- To evaluate the safety and effectiveness of mangafodipir in imaging studies of nerve
disorders affecting the eye and brain.
Eligibility:
- Individuals between 18 and 70 years of age who either have been diagnosed with multiple
sclerosis or are healthy volunteers.
Design:
- Participants will be screened with a physical examination, medical history, and blood
tests.
- Participants will have up to 10 outpatient visits for screening and MRI scans over a
period of up to 2 months. Participants will be divided into Eye and Brain groups, based
on which area will be studied during the scans. (Participants who have available time
may be eligible for study in both groups.)
- Participants will have an initial MRI scan as part of the screening process.
- At the first visit, participants will have a baseline MRI scan once before receiving
mangafodipir.
- Participants will have up to five MRI scans, with the following procedures:
- Eye imaging group: MRI scans will be scheduled at specific times between 2 and 48 hours
after receiving mangafodipir. Eye MRI participants will wear a dark contact lens and an
eye patch for 30 minutes before receiving mangafodipir, and leave both on for up to 8
hours. The other eye will remain uncovered.
- Brain imaging group: MRI scans will be scheduled at specific times between 48 hours and
7 days after receiving mangafodipir.
- Participants will have a follow-up MRI scan 1 month after receiving mangafodipir. This
scan is done to see how long mangafodipir may affect MRI images of the brain.
- Contrast agents are drugs that make certain body areas or abnormalities show up better on
imaging studies, such as magnetic resonance imaging (MRI) scans. Mangafodipir is an MRI
contrast agent with manganese that has been approved for MRI scans of the liver and pancreas.
Because contrast agents with manganese have also been shown to be useful in studying problems
with the nervous system, researchers are interested in determining if mangafodipir may be
used for MRI scans of the brain or eye, two areas that often experience problems caused by
disorders that affect the nervous system, such as multiple sclerosis. However, more
information is needed on whether mangafodipir will be useful for this purpose, or how best to
use it in MRI scans of the eye and brain. To study mangafodipir more closely, researchers are
interested in studying its use in both individuals with multiple sclerosis and healthy
volunteers.
Background:
- Contrast agents are drugs that make certain body areas or abnormalities show up better on
imaging studies, such as magnetic resonance imaging (MRI) scans. Mangafodipir is an MRI
contrast agent with manganese that has been approved for MRI scans of the liver and pancreas.
Because contrast agents with manganese have also been shown to be useful in studying problems
with the nervous system, researchers are interested in determining if mangafodipir may be
used for MRI scans of the brain or eye, two areas that often experience problems caused by
disorders that affect the nervous system, such as multiple sclerosis. However, more
information is needed on whether mangafodipir will be useful for this purpose, or how best to
use it in MRI scans of the eye and brain. To study mangafodipir more closely, researchers are
interested in studying its use in both individuals with multiple sclerosis and healthy
volunteers.
Objectives:
- To evaluate the safety and effectiveness of mangafodipir in imaging studies of nerve
disorders affecting the eye and brain.
Eligibility:
- Individuals between 18 and 70 years of age who either have been diagnosed with multiple
sclerosis or are healthy volunteers.
Design:
- Participants will be screened with a physical examination, medical history, and blood
tests.
- Participants will have up to 10 outpatient visits for screening and MRI scans over a
period of up to 2 months. Participants will be divided into Eye and Brain groups, based
on which area will be studied during the scans. (Participants who have available time
may be eligible for study in both groups.)
- Participants will have an initial MRI scan as part of the screening process.
- At the first visit, participants will have a baseline MRI scan once before receiving
mangafodipir.
- Participants will have up to five MRI scans, with the following procedures:
- Eye imaging group: MRI scans will be scheduled at specific times between 2 and 48 hours
after receiving mangafodipir. Eye MRI participants will wear a dark contact lens and an
eye patch for 30 minutes before receiving mangafodipir, and leave both on for up to 8
hours. The other eye will remain uncovered.
- Brain imaging group: MRI scans will be scheduled at specific times between 48 hours and
7 days after receiving mangafodipir.
- Participants will have a follow-up MRI scan 1 month after receiving mangafodipir. This
scan is done to see how long mangafodipir may affect MRI images of the brain.
Objective
The original goals of this pilot study were to assess whether: (1) manganese-enhanced
magnetic resonance imaging (MEMRI) using mangafodipir trisodium, a contrast agent that enters
the intracellular compartment, can detect multiple sclerosis-related tissue damage in the
retina, optic nerve, and brain; and (2) the MRI effects of manganese are detectable in the
basal ganglia one month following administration. With amendment F, the retina and optic
nerve portions of the study have been eliminated, and we have modified our focus to
examination of participants with multiple sclerosis and MRI evidence of abnormal permeability
to gadolinium. In these individuals, mangafodipir may allow assessment of brain connectivity
that is not possible to achieve with a gadolinium-based contrast agent, which remains in the
extracellular space.
Study Population
Up to 15 healthy volunteers and up to 15 participants with multiple sclerosis.
Design
The first phase of the study involved healthy volunteers and focuses on optimizing our
imaging protocol. The second phase studies participants with multiple sclerosis. With
amendment F, the focus has shifted to evaluating participants with multiple sclerosis and
evidence of gadolinium enhancement on contrast-enhanced brain MRI.
We have completed enrollment of 15 healthy volunteers. With Amendment G, we will remove
references to the enrollment and screening procedures for healthy volunteers.
Outcome Measures
The primary outcome measure is T1-weighted signal intensity, measured: (1) in the retina,
optic nerve, and brain at early time points after mangafodipir administration; and (2) in the
basal ganglia, cerebral cortex, and whole brain one month following administration.
The original goals of this pilot study were to assess whether: (1) manganese-enhanced
magnetic resonance imaging (MEMRI) using mangafodipir trisodium, a contrast agent that enters
the intracellular compartment, can detect multiple sclerosis-related tissue damage in the
retina, optic nerve, and brain; and (2) the MRI effects of manganese are detectable in the
basal ganglia one month following administration. With amendment F, the retina and optic
nerve portions of the study have been eliminated, and we have modified our focus to
examination of participants with multiple sclerosis and MRI evidence of abnormal permeability
to gadolinium. In these individuals, mangafodipir may allow assessment of brain connectivity
that is not possible to achieve with a gadolinium-based contrast agent, which remains in the
extracellular space.
Study Population
Up to 15 healthy volunteers and up to 15 participants with multiple sclerosis.
Design
The first phase of the study involved healthy volunteers and focuses on optimizing our
imaging protocol. The second phase studies participants with multiple sclerosis. With
amendment F, the focus has shifted to evaluating participants with multiple sclerosis and
evidence of gadolinium enhancement on contrast-enhanced brain MRI.
We have completed enrollment of 15 healthy volunteers. With Amendment G, we will remove
references to the enrollment and screening procedures for healthy volunteers.
Outcome Measures
The primary outcome measure is T1-weighted signal intensity, measured: (1) in the retina,
optic nerve, and brain at early time points after mangafodipir administration; and (2) in the
basal ganglia, cerebral cortex, and whole brain one month following administration.
- This study enrolls two cohorts:
- Up to 15 healthy volunteers
- Up to 15 MS patients
INCLUSION CRITERIA:
- Age 18 to 70 (inclusive)
- Able to give informed consent
- Able to comply with study procedures
- Diagnosis of multiple sclerosis according to the current McDonald Criteria
- Evidence of abnormal permeability of the brain or cerebrospinal fluid, based on a
screening gadolinium-enhacned MRI scancan
EXCLUSION CRITERIA:
- Reported history of clinically significant medical disorders, such as liver or kidney
disease, that could potentially increase the risk of CNS damage due to manganese
exposure
- Uncontrolled hypertension, demonstrated by a blood pressure reading of >160/100 at
screening on repeat exam
- Screening labs demonstrating any value for hepatic or biliary function out of the
range of normal, to include AST, ALT, bilirubin, gammaGT, alkaline phosphatase; repeat
value of the same test showing normal results will remove the exclusion
- For patients receiving ocular MRI, reported history of ocular disorders
- Previous or current alcohol and/or substance abuse
- Previous presumed occupational exposure to manganese (i.e., having worked in a mine,
foundry, smelter, dry cell battery manufacturing facility, or agriculture)
- Medical contraindications for MRI (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 are not MRI-safe or that cannot be removed)
- Psychological contraindications for MRI (e.g., claustrophobia), to be assessed at the
time the medical history is collected
- Pregnancy or current breastfeeding
- Allergy to manganese
- Reported history of impaired hearing, because people with impaired hearing are at
increased risk of sound-induced damage from the MRI scanner
- Ongoing treatment with calcium-channel blockers
- Clinically significant iron-deficiency anemia
- 5 contrast-enhancing lesion on screening MRI performed within one week of
administration of mangafodipir
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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