Multiple SclerosisNCT02659956
Pathological Basis of MRI Signal Changes in Multiple Sclerosis
An observational study of Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Multiple sclerosis (MS) is a disease that damages the central nervous system (brain and spinal cord). This leads to increased physical disability over time. The disease is lifelong once it begins. Researchers want to learn more about MS s stages and follow them until a person s death. Read more about this study
- Who is it for?
- Ages 18 to 120 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- How many people
- 250 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Apr 2016to 26 Feb 2080
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 120 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Primary clinical
Who may be able to join
- Diagnosis of MS according to consensus criteria at the time of enrollment OR diagnosis of a disease that shares clinical, imaging, or biological features with MS OR individuals without known CNS disease.
- Age greater than or equal to 18.
- Able to participate in study procedures and provide high-quality clinical research data (for example, prior MRI scans show ability to tolerate the MRI scan with minimal motion artifact).
- Willing to return to NIH for follow-up visits approximately annually (or every 5 years for non-CNS controls) until the time of autopsy. Note: participants who become too sick to return to NIH will not be removed from the study.
- Willing to undergo autopsy with donation of at least the brain, spinal cord, and retinas.
- Able to provide informed consent at the time of initial study enrollment and willing to appoint a Durable Power of Attorney (DPA) if an advanced directive is not already in place.
- Except for non-CNS controls, simultaneously participating in another screening or natural history protocol within the NINDS Neuroimmunology Clinic at the time of study entry.
- Eligible NIH employees and staff may participate.
Who cannot join
- Unwilling to allow sharing and/or use in future studies of coded samples and data that are collected for this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: The Pathological Basis of MRI Signal Changes in Multiple Sclerosis: A Longitudinal In Vivo-to-Postmortem Study
Background:
Multiple sclerosis (MS) is a disease that damages the central nervous system (brain and spinal cord). This leads to increased physical disability over time. The disease is lifelong once it begins. Researchers want to learn more about MS s stages and follow them until a person s death.
Read more
Objective:
To understand how the physical and clinical signs of MS relate to its changes over time.
Eligibility:
Adults age 18 or older with MS or a disease of the brain and spinal cord that may act like MS.
Design:
Participants will have a medical history and a complete neurological exam. They may have timed tests of neurological function, such as a 25-foot walk and a 9-hole peg test.
Participants will have multi-day visits about once a year.
Participants will have blood drawn.
Participants may have a brain magnetic resonance imaging (MRI) scan. They may also have an MRI of the spinal cord. They may get a contrast agent (dye) injected into a tube in an arm vein. During the MRI, participants will lie on a table that slides in and out of a metal cylinder.
Participants will have the thickness of their retina measured using optical coherence tomography. A camera on top of a table uses lasers. Participants will look through a lens and follow instructions. Eye drops may be used to dilate the pupils.
Participants will chew on a piece of sterile cotton for 1 minute to collect saliva.
Participants agree to have an autopsy at the time of their death and to donate some of their organs to research, such as the brain and spinal cord.
Read the detailed description
Objective.
The goal of this protocol is to understand how the pathology of multiple sclerosis (MS) relates to its evolution over time as observed through neuroradiological, clinical, and biological data collection in vivo.
Study population.
This study will enroll up to 200 individuals with MS, targeting 100 study completers, across various ages and stages of the disease, as well as up to 50 appropriate disease and non-neurological control participants, for a total of 250 participants.
Design.
This is a longitudinal cohort study in which participants will be seen approximately annually at the NIH Clinical Center. Most visits will extend over several days. Participants will receive ongoing care by their outside clinician. They may also concurrently participate in additional research protocols at the NIH or elsewhere, and data may be shared between those protocols and the current one. At the time of death, the central nervous system (CNS) (brain, spinal cord, retinas, and cerebrospinal fluid), as well as lymph nodes and possibly other lymphoid tissue, will be harvested.
This is a multi-site study with Johns Hopkins University. Some analysis of identifiable data will be conducted at Johns Hopkins University JHU under a reliance agreement. Patients will not be consented to the study or participate in study interventions/procedures at JHU.
Outcome measures.
Outcome measures include data derived from magnetic resonance imaging (MRI) of the brain and spinal cord, optical coherence tomography (OCT) of the retinas, clinical examination, and disability scales; radiological and pathological examination of CNS tissue; and the correlation between in vivo and postmortem measures. Particular attention will be paid to the extent to which longitudinal in vivo changes predict postmortem findings.
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Longitudinal Prospective Follow-Up, Natural History
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Individuals without known CNS disease | Family members of patient participants | |
| Patient controls | A target population of 100 patient controls will also be enrolled. These individuals will have diseases that share clinical, imaging, or biological features with MS. | |
| Patients with multiple sclerosis | Up to 250 adults (age >= 18) with MS, diagnosed by applicable consensus criteria and by the best judgment of the investigators at the time of enrollment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation among in vivo imaging, postmortem imaging, and pathological characteristics of individual areas of tissue damage ("lesions") in the brain, spinal cord, and retinas.
Correlation among in vivo imaging, postmortem imaging, and pathological characteristics of individual areas of tissue damage ( lesions ) in the brain, spinal cord, and retinas. Priority will be given to measures of myelination, axonal preservation, inflammation, and astrogliosis, as judged primarily by histological stains and immunohistochemistry.
Measured: annual visits
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2016 (estimated)
- Study start7 Apr 2016
- Primary completion26 Feb 2080 (estimated)
- Study completion26 Feb 2080 (estimated)
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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 250 participants (estimated)
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
- NCT02659956
- Sponsor's protocol ID
- 160055
- Other IDs
- 16-N-0055
- Status last verified
- 3 Jun 2026
- First submitted
- 20 Jan 2016
- Last updated
- 5 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: This is a natural history study, not a clinical trial.
Publications
Absinta M, Nair G, Filippi M, Ray-Chaudhury A, Reyes-Mantilla MI, Pardo CA, Reich DS. Postmortem magnetic resonance imaging to guide the pathologic cut: individualized, 3-dimensionally printed cutting boxes for fixed brains. J Neuropathol Exp Neurol. 2014 Aug;73(8):780-8. doi: 10.1097/NEN.0000000000000096.
PubMed 25007244Absinta M, Vuolo L, Rao A, Nair G, Sati P, Cortese IC, Ohayon J, Fenton K, Reyes-Mantilla MI, Maric D, Calabresi PA, Butman JA, Pardo CA, Reich DS. Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis. Neurology. 2015 Jul 7;85(1):18-28. doi: 10.1212/WNL.0000000000001587. Epub 2015 Apr 17.
PubMed 25888557Maggi P, Macri SM, Gaitan MI, Leibovitch E, Wholer JE, Knight HL, Ellis M, Wu T, Silva AC, Massacesi L, Jacobson S, Westmoreland S, Reich DS. The formation of inflammatory demyelinated lesions in cerebral white matter. Ann Neurol. 2014 Oct;76(4):594-608. doi: 10.1002/ana.24242. Epub 2014 Aug 21.
PubMed 25088017
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Pathological Basis of MRI Signal Changes in Multiple Sclerosis: A Longitudinal In Vivo-to-Postmortem Study
- ClinicalTrials.gov ID
- NCT02659956
- Acronym / sponsor ID
- 160055
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Longitudinal Prospective Follow-Up, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 7 Apr 2016 (actual)
- Primary completion
- 26 Feb 2080 (estimated)
- Study completion
- 26 Feb 2080 (estimated)
- First posted
- 21 Jan 2016 (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:
Multiple sclerosis (MS) is a disease that damages the central nervous system (brain and spinal cord). This leads to increased physical disability over time. The disease is lifelong once it begins. Researchers want to learn more about MS s stages and follow them until a person s death.
Objective:
To understand how the physical and clinical signs of MS relate to its changes over time.
Eligibility:
Adults age 18 or older with MS or a disease of the brain and spinal cord that may act like MS.
Design:
Participants will have a medical history and a complete neurological exam. They may have timed tests of neurological function, such as a 25-foot walk and a 9-hole peg test.
Participants will have multi-day visits about once a year.
Participants will have blood drawn.
Participants may have a brain magnetic resonance imaging (MRI) scan. They may also have an MRI of the spinal cord. They may get a contrast agent (dye) injected into a tube in an arm vein. During the MRI, participants will lie on a table that slides in and out of a metal cylinder.
Participants will have the thickness of their retina measured using optical coherence tomography. A camera on top of a table uses lasers. Participants will look through a lens and follow instructions. Eye drops may be used to dilate the pupils.
Participants will chew on a piece of sterile cotton for 1 minute to collect saliva.
Participants agree to have an autopsy at the time of their death and to donate some of their organs to research, such as the brain and spinal cord.
Detailed description
Objective.
The goal of this protocol is to understand how the pathology of multiple sclerosis (MS) relates to its evolution over time as observed through neuroradiological, clinical, and biological data collection in vivo.
Study population.
This study will enroll up to 200 individuals with MS, targeting 100 study completers, across various ages and stages of the disease, as well as up to 50 appropriate disease and non-neurological control participants, for a total of 250 participants.
Design.
This is a longitudinal cohort study in which participants will be seen approximately annually at the NIH Clinical Center. Most visits will extend over several days. Participants will receive ongoing care by their outside clinician. They may also concurrently participate in additional research protocols at the NIH or elsewhere, and data may be shared between those protocols and the current one. At the time of death, the central nervous system (CNS) (brain, spinal cord, retinas, and cerebrospinal fluid), as well as lymph nodes and possibly other lymphoid tissue, will be harvested.
This is a multi-site study with Johns Hopkins University. Some analysis of identifiable data will be conducted at Johns Hopkins University JHU under a reliance agreement. Patients will not be consented to the study or participate in study interventions/procedures at JHU.
Outcome measures.
Outcome measures include data derived from magnetic resonance imaging (MRI) of the brain and spinal cord, optical coherence tomography (OCT) of the retinas, clinical examination, and disability scales; radiological and pathological examination of CNS tissue; and the correlation between in vivo and postmortem measures. Particular attention will be paid to the extent to which longitudinal in vivo changes predict postmortem findings.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Individuals without known CNS disease | – | –Family members of patient participants |
| Patient controls | – | –A target population of 100 patient controls will also be enrolled. These individuals will have diseases that share clinical, imaging, or biological features with MS. |
| Patients with multiple sclerosis | – | –Up to 250 adults (age >= 18) with MS, diagnosed by applicable consensus criteria and by the best judgment of the investigators at the time of enrollment. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Primary clinical
Key inclusion criteria (8 listed)
- Diagnosis of MS according to consensus criteria at the time of enrollment OR diagnosis of a disease that shares clinical, imaging, or biological features with MS OR individuals without known CNS disease.
- Age greater than or equal to 18.
- Able to participate in study procedures and provide high-quality clinical research data (for example, prior MRI scans show ability to tolerate the MRI scan with minimal motion artifact).
- Willing to return to NIH for follow-up visits approximately annually (or every 5 years for non-CNS controls) until the time of autopsy. Note: participants who become too sick to return to NIH will not be removed from the study.
- Willing to undergo autopsy with donation of at least the brain, spinal cord, and retinas.
Key exclusion criteria (1 listed)
- Unwilling to allow sharing and/or use in future studies of coded samples and data that are collected for this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Correlation among in vivo imaging, postmortem imaging, and pathological characteristics of individual areas of tissue damage ("lesions") in the brain, spinal cord, and retinas.
Time frame: annual visits
Correlation among in vivo imaging, postmortem imaging, and pathological characteristics of individual areas of tissue damage ( lesions ) in the brain, spinal cord, and retinas. Priority will be given to measures of myelination, axonal preservation, inflammation, and astrogliosis, as judged primarily by histological stains and immunohistochemistry.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2026.
- Background: PubMed 25007244Absinta M, Nair G, Filippi M, Ray-Chaudhury A, Reyes-Mantilla MI, Pardo CA, Reich DS. Postmortem magnetic resonance imaging to guide the pathologic cut: individualized, 3-dimensionally printed cutting boxes for fixed brains. J Neuropathol Exp Neurol. 2014 Aug;73(8):780-8. doi: 10.1097/NEN.0000000000000096.
- Background: PubMed 25888557Absinta M, Vuolo L, Rao A, Nair G, Sati P, Cortese IC, Ohayon J, Fenton K, Reyes-Mantilla MI, Maric D, Calabresi PA, Butman JA, Pardo CA, Reich DS. Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis. Neurology. 2015 Jul 7;85(1):18-28. doi: 10.1212/WNL.0000000000001587. Epub 2015 Apr 17.
- Background: PubMed 25088017Maggi P, Macri SM, Gaitan MI, Leibovitch E, Wholer JE, Knight HL, Ellis M, Wu T, Silva AC, Massacesi L, Jacobson S, Westmoreland S, Reich DS. The formation of inflammatory demyelinated lesions in cerebral white matter. Ann Neurol. 2014 Oct;76(4):594-608. doi: 10.1002/ana.24242. Epub 2014 Aug 21.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No. This is a natural history study, not a clinical trial.
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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.
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?
An observational study of 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 8 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 5 Jun 2026. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jenifer E Dwyer ((301) 496-3825, jenifer.dwyer@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation among in vivo imaging, postmortem imaging, and pathological characteristics of individual areas of tissue damage ("lesions") in the brain, spinal cord, and retinas. (time frame: annual visits). 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 NCT02659956, 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 5 Jun 2026.