Multiple SclerosisPhase 1NCT01326715
Manganese-Enhanced Magnetic Resonance Imaging in Healthy Volunteers and People With Multiple Sclerosis
A Phase 1 study testing Mangafodipir (Teslascan) in people with Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Mangafodipir (Teslascan)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Oct 2013to 13 Sep 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Multiple Sclerosis
- Being tested
- Mangafodipir (Teslascan)
- Keywords
- Mangafodipir, Brain, MEMRI, Healthy Volunteer, Multiple Sclerosis
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mangafodipir (Teslascan)Drug
gadolinium enhancement on contrast enhanced brain MRI.
| Study group | Role | What they receive |
|---|---|---|
| mangafodipir | Active comparator | see protocol Receives: Drug: Mangafodipir (Teslascan) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: early time points after mangafodipir administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2011 (estimated)
- Study start17 Oct 2013
- Primary completion18 Sep 2019
- Study completion13 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Daniel S Reich, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01326715
- Sponsor's protocol ID
- 110116
- Other IDs
- 11-N-0116
- Status last verified
- Sep 2022
- First submitted
- 30 Mar 2011
- Last updated
- 16 Sep 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 15694681Aoki 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.
PubMed 15219577Aschner 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.
PubMed 17466353
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Manganese-Enhanced Magnetic Resonance Imaging in Healthy Volunteers and People With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT01326715
- Acronym / sponsor ID
- 110116
- Conditions
- Multiple Sclerosis
- Keywords
- Mangafodipir, Brain, MEMRI, Healthy Volunteer, Multiple Sclerosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 17 Oct 2013 (actual)
- Primary completion
- 18 Sep 2019 (actual)
- Study completion
- 13 Sep 2022 (actual)
- First posted
- 31 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| mangafodipir | Active comparator | Drug: Mangafodipir (Teslascan)see protocol |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mangafodipir (Teslascan)gadolinium enhancement on contrast enhanced brain MRI. | Drug | mangafodipir |
Primary outcome
The primary outcome measure is normalized T1-weighted signal intensity.
Time frame: early time points after mangafodipir administration
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2022.
- Background: PubMed 15694681Andrews 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.
- Background: PubMed 15219577Aoki 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.
- Background: PubMed 17466353Aschner 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel S Reich, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mangafodipir (Teslascan) in people with Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome measure is normalized T1-weighted signal intensity. (time frame: early time points after mangafodipir administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01326715, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2022.