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Pathological Basis of MRI Signal Changes in 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02659956
Recruitment Status : Recruiting
First Posted : January 21, 2016
Last Update Posted : August 3, 2022
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Brief Summary:


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.


To understand how the physical and clinical signs of MS relate to its changes over time.


Adults age 18 or older with MS or a disease of the brain and spinal cord that may act like MS.


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.

Condition or disease
Multiple Sclerosis

Detailed Description:


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 150 individuals with MS, targeting 50 study completers, across various ages and stages of the disease, as well as 50 appropriate disease and non-neurological control participants, for a total of 200 participants.


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.

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Pathological Basis of MRI Signal Changes in Multiple Sclerosis: A Longitudinal In Vivo-to-Postmortem Study
Actual Study Start Date : April 7, 2016
Estimated Primary Completion Date : February 26, 2080
Estimated Study Completion Date : February 26, 2080

Resource links provided by the National Library of Medicine

Individuals without known CNS disease
Family members of patient participants
Patient controls
a target population of 50 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 150 adults (age >= 18) with MS, diagnosed by applicable consensus criteria, and by the best judgment of the investigators, at the time of enrollment.

Primary Outcome Measures :
  1. 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.

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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Primary clinical
  • 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.


Unwilling to allow sharing and/or use in future studies of coded samples and data that are collected for this study.

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 identifier (NCT number): NCT02659956

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Contact: Joan M Ohayon, C.R.N.P. (301) 496-9135
Contact: Daniel S Reich, M.D. (301) 496-1801

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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   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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Principal Investigator: Daniel S Reich, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
Additional Information:
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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS) Identifier: NCT02659956    
Other Study ID Numbers: 160055
First Posted: January 21, 2016    Key Record Dates
Last Update Posted: August 3, 2022
Last Verified: March 7, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: .This is a natural history study, not a clinical trial.

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Studies a U.S. FDA-regulated Drug Product: No
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) ):
Multiple Sclerosis
Longitudinal Prospective Follow-Up
Natural History
Additional relevant MeSH terms:
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Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases