Manganese-Enhanced Magnetic Resonance Imaging in Healthy Volunteers and People With Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Mangafodipir (Teslascan)
Intervention type(s): Drug
Intervention description(s): gadolinium enhancement on contrast enhanced brain MRI.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Mangafodipir; Brain; MEMRI; Healthy Volunteer; Multiple Sclerosis