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

NCT01326715 | Completed Phase 1 FDA Drug

• 2 other identifiers: 11011611-N-0116
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Keywords

Mangafodipir; Brain; MEMRI; Healthy Volunteer; Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• The primary outcome measure is normalized T1-weighted signal intensity.

  T1#weighted signal intensity, measured in selected brain structures at early time points after mangafodipir administration, as well as inthe basal ganglia, cerebral cortex, and whole brain one month following administration.

  early time points after mangafodipir administration

Study Arms (1)

mangafodipir

ACTIVE COMPARATOR

see protocol

Drug: Mangafodipir (Teslascan)

Interventions

Mangafodipir (Teslascan) DRUG

gadolinium enhancement on contrast enhanced brain MRI.

mangafodipir

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• contrast-enhancing lesion on screening MRI performed within one week of administration of mangafodipir

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Andrews HE, Nichols PP, Bates D, Turnbull DM. Mitochondrial dysfunction plays a key role in progressive axonal loss in Multiple Sclerosis. Med Hypotheses. 2005;64(4):669-77. doi: 10.1016/j.mehy.2004.09.001.

  PMID: 15694681 BACKGROUND

• Aoki I, Wu YJ, Silva AC, Lynch RM, Koretsky AP. In vivo detection of neuroarchitecture in the rodent brain using manganese-enhanced MRI. Neuroimage. 2004 Jul;22(3):1046-59. doi: 10.1016/j.neuroimage.2004.03.031.

  PMID: 15219577 BACKGROUND

• Aschner M, Guilarte TR, Schneider JS, Zheng W. Manganese: recent advances in understanding its transport and neurotoxicity. Toxicol Appl Pharmacol. 2007 Jun 1;221(2):131-47. doi: 10.1016/j.taap.2007.03.001. Epub 2007 Mar 12.

  PMID: 17466353 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Daniel S Reich, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2011
• First Posted: March 31, 2011
• Study Start: October 17, 2013
• Primary Completion: September 18, 2019
• Study Completion: September 13, 2022
• Last Updated: September 16, 2022

Record last verified: 2022-09

Locations

US (1)