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

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ClinicalTrials.gov Identifier: NCT01326715
Recruitment Status : Recruiting
First Posted : March 31, 2011
Last Update Posted : May 30, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Brief 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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: Mangafodipir (Teslascan) Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Manganese-Enhanced Magnetic Resonance Imaging in Healthy Volunteers and People With Multiple Sclerosis
Actual Study Start Date : October 17, 2013
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : June 1, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Manganese

Arm Intervention/treatment
Active Comparator: mangafodipir
see protocol
Drug: Mangafodipir (Teslascan)
Contrast Agent




Primary Outcome Measures :
  1. The primary outcome measure is normalized T1-weighted signal intensity. [ Time Frame: One month after mangafodipir administration ]

Secondary Outcome Measures :
  1. Optimum scanning time points following mangafodipir administration [ Time Frame: Within the first week after injection ]
  2. Qualitative and quantitative assessment of improved lesion visualization by MEMRI (i.e., enhancement pattern). [ Time Frame: Within the first week after injection ]
  3. Differences in enhancement patterns between healthy volunteers and people with MS. [ Time Frame: ongoing ]
  4. Qualitative differences between enhancement patterns induced byadministration of 2013 batch and 2015 batch mangafodipir. [ Time Frame: ongoing ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01326715


Contacts
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Contact: Irene CM Cortese, M.D. (301) 496-9175 corteseir@ninds.nih.gov
Contact: Daniel S Reich, M.D. (301) 496-1801 reichds@ninds.nih.gov

Locations
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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 Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Daniel S Reich, M.D. National Institutes of Health Clinical Center (CC)

Additional Information:
Publications:
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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT01326715     History of Changes
Other Study ID Numbers: 110116
11-N-0116
First Posted: March 31, 2011    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: April 16, 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Mangafodipir
Brain
MEMRI
Healthy Volunteer
Multiple Sclerosis
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Manganese
Pyridoxal Phosphate
Edetic Acid
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins