Manganese-Enhanced Magnetic Resonance Imaging in Healthy Volunteers and People With Multiple Sclerosis

This study is currently recruiting participants.
Verified August 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier:
NCT01326715
First received: March 30, 2011
Last updated: March 14, 2014
Last verified: August 2013
  Purpose

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.

Condition Intervention Phase
Multiple Sclerosis
Optic Neuritis
Drug: Mangafodipir (Teslascan)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Manganese-Enhanced Magnetic Resonance Imaging in Healthy Volunteers and People With Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • MRI changes after mangafodipir administration MRI changes after mangafodipir administration [ Time Frame: 1 day - 1 week ] [ Designated as safety issue: No ]
  • MRI changes in the brain after mangafodipir administration [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Optimum scanning times [ Time Frame: 1 day - 1 week ] [ Designated as safety issue: No ]
  • Correlation w/ Vision Measures [ Time Frame: 1 day - 1 week ] [ Designated as safety issue: No ]
  • Assessment of lesion visualization [ Time Frame: 1 day - 1 week ] [ Designated as safety issue: No ]
  • Differences in MRI Enhancement Pattern between healthy volunteers and people with MS [ Time Frame: 1 day - 1 week ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: March 2011
Estimated Study Completion Date: December 2014
Intervention Details:
    Drug: Mangafodipir (Teslascan)
    Contrast Agent
Detailed Description:

Objective

The goals of this pilot study are to assess whether: (1) manganese-enhanced magnetic resonance imaging (MEMRI) using mangafodipir trisodium 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.

Study Population

Up to 10 healthy volunteers and up to 15 participants with multiple sclerosis.

Design

The first phase of the study will involve healthy volunteers and will focus on optimizing our imaging protocol. The second phase will study participants with multiple sclerosis.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

HEALTHY VOLUNTEER:

Age between 18 and 70

Vital signs within normal range at the time of the screening visit

Normal complete blood count and normal kidney and liver function tests

Able to give informed consent

For retinal imaging studies, corrected visual acuity of 20/30 or better

For retinal imaging studies, intraocular pressure between 11 and 19 mm Hg

Normal screening brain MRI

PATIENT:

Age between 18 and 70

Vital signs within normal range at the time of the screening visit

Normal complete blood count and normal kidney and liver function tests

Able to give informed consent

For retinal imaging studies, intraocular pressure between 11 and 19 mm Hg

Diagnosis of multiple sclerosis according to revised McDonald Criteria

Expanded disability status scale (EDSS) 0-6

EXCLUSION CRITERIA:

HEALTHY VOLUNTEER:

Reported history of systemic, ocular, or central-nervous-system disorders

Screening labs demonstrating any value for hepatic or biliary function out of the range of normal, to include AST, ALT, bilirubin, gammaGT, alkaline phosphatase

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 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

Family history of Parkinson s Disease or other neurodegenerative disease

Ongoing treatment with calcium-channel blockers

Iron-deficiency anemia

PATIENT:

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

Screening labs demonstrating any value for hepatic or biliary function out of the range of normal, to include AST, ALT, bilirubin, gammaGT, alkaline phosphatase

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 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

Greater than 1 contrast-enhancing lesion on screening MRI performed within one week of administration of mangafodipir

On-going treatment with calcium-channel blocker

Iron-deficiency anemia

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01326715

Contacts
Contact: Irene CM Cortese, M.D. (301) 496-0064 corteseir@ninds.nih.gov
Contact: Daniel S Reich, M.D. (301) 496-1801 reichds@ninds.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Daniel S Reich, M.D. National Institutes of Health Clinical Center (CC)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier: NCT01326715     History of Changes
Other Study ID Numbers: 110116, 11-N-0116
Study First Received: March 30, 2011
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Multiple Sclerosis
MRI
Manganese Enhanced MRI
Optic Neuritis
Healthy Volunteer

Additional relevant MeSH terms:
Multiple Sclerosis
Neuritis
Optic Neuritis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Optic Nerve Diseases
Cranial Nerve Diseases
Eye Diseases
Pathologic Processes
Manganese
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014