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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01326715
Recruitment Status : Completed
First Posted : March 31, 2011
Last Update Posted : February 28, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Tracking Information
First Submitted Date  ICMJE March 30, 2011
First Posted Date  ICMJE March 31, 2011
Last Update Posted Date February 28, 2020
Actual Study Start Date  ICMJE October 17, 2013
Actual Primary Completion Date September 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 17, 2019)
The primary outcome measure is normalized T1-weighted signal intensity. [ Time Frame: One month after mangafodipir administration ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 30, 2011)
  • MRI changes after mangafodipir administration MRI changes after mangafodipir administration [ Time Frame: 1 day - 1 week ]
  • MRI changes in the brain after mangafodipir administration [ Time Frame: 1 month ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2019)
  • Optimum scanning time points following mangafodipir administration [ Time Frame: Within the first week after injection ]
  • Qualitative and quantitative assessment of improved lesion visualization by MEMRI (i.e., enhancement pattern). [ Time Frame: Within the first week after injection ]
  • Differences in enhancement patterns between healthy volunteers and people with MS. [ Time Frame: ongoing ]
  • Qualitative differences between enhancement patterns induced byadministration of 2013 batch and 2015 batch mangafodipir. [ Time Frame: ongoing ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2011)
  • Optimum scanning times [ Time Frame: 1 day - 1 week ]
  • Correlation w/ Vision Measures [ Time Frame: 1 day - 1 week ]
  • Assessment of lesion visualization [ Time Frame: 1 day - 1 week ]
  • Differences in MRI Enhancement Pattern between healthy volunteers and people with MS [ Time Frame: 1 day - 1 week ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Manganese-Enhanced Magnetic Resonance Imaging in Healthy Volunteers and People With Multiple Sclerosis
Official Title  ICMJE Manganese-Enhanced Magnetic Resonance Imaging in Healthy Volunteers and People With Multiple Sclerosis
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE Drug: Mangafodipir (Teslascan)
Contrast Agent
Study Arms  ICMJE Active Comparator: mangafodipir
see protocol
Intervention: Drug: Mangafodipir (Teslascan)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 1, 2019)
15
Original Estimated Enrollment  ICMJE
 (submitted: March 30, 2011)
25
Actual Study Completion Date  ICMJE September 30, 2019
Actual Primary Completion Date September 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01326715
Other Study ID Numbers  ICMJE 110116
11-N-0116
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
Study Sponsor  ICMJE National Institute of Neurological Disorders and Stroke (NINDS)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Daniel S Reich, M.D. National Institutes of Health Clinical Center (CC)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date September 30, 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP