Magnetic Resonance Imaging (MRI) to Evaluate Activity of Multiple Sclerosis (MS)

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: NCT00001248
Recruitment Status : Recruiting
First Posted : November 4, 1999
Last Update Posted : December 6, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Brief Summary:

Studies performed under 89-N-0045 are designed to examine the natural history of multiple sclerosis (MS) using MRI and immunological measures. In addition to studying the natural history of untreated patients, the natural history of patients receiving approved disease-modifying therapies of MS will be examined. In both cohorts of patients levels of disease activity on MRI will be compared with immunological characteristics in order to help identify disease mechanism. Patients with either definite MS (based either on clinical or combined clinical and MRI criteria) or with an initial presentation of neurological dysfunction consistent with MS will be studied longitudinally by MRI. Disease activity on MRI will be assessed using several MRI measures of disease activity including the number of contrast enhancing lesions, the overall burden of disease, brain atrophy and measures to assess axonal damage. Patients will be assessed clinically and correlations between immunological and genetic factors and disease activity as seen clinically or by MRI will be studied.

A second cohort of patients starting the use of approved therapy will also be examined. Patients referred to NIH prior to beginning approved therapy will be assessed with a series of three monthly MRIs to determine the level of pretreatment disease activity. After beginning approved therapy under the direction of their private physician, patients will be followed similarly to the natural history cohort. Immunological and genetic findings will be accessed before and during therapy in order to help establish the mechanisms of action of the therapies and to identify mechanisms accounting for either a response or lack of response to therapy. Part of the collected samples willl be cryopreserved to provide respository for further studies focusing on detection of biomarkers indicative of disease state, disease stage or repsonse to therapies.

Additionally, a cohort of normal volunteers will be studied. The studies in the normal volunteers will be used to establish the most appropriate imaging sequences for studying normal white matter in MS patients using magnetization transfer (MT) imaging sequences for studying normal white matter in MS patients using magnetization transfer (MT) imaging and to provide normative immunological measures.

Condition or disease
Multiple Sclerosis

Detailed Description:

Studies performed under 89-N-0045 are primarily designed to examine the natural history of multiple sclerosis (MS) and its mimickers, viewed through the window of imaging (especially magnetic resonance imaging or MRI). The protocol has four other important objectives: (1) Screening prospective participants in selected Neuroimmunology Branch clinical trials; (2) Performing studies to help define the mechanism of action and cause of side effects of disease modifying therapies (DMT); (3) Studying healthy volunteers for comparison with patients and for development of new experimental technologies; and (4) Comparing MS to other neurological diseases that share imaging features.

Disease activity on MRI will be assessed using several MRI measures, focusing on the number of new on-study lesions but also including the number of contrast-enhancing lesions, the total number of MRI-visible lesions, brain atrophy, and more recently defined MRI measures of tissue damage, such as quantitative magnetic relaxation mapping, diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI), and MR spectroscopy (MRS). Additionally, participants will be assessed with other imaging modalities, specifically optical coherence tomography (OCT) and fluorescein angiography of the eye, and they will also be studied clinically and with neurophysiologic tests.

In order to obtain comparative data for proper interpretation of the results in MS, two control cohorts one consisting of patients, the other of healthy volunteers will be studied. The patient control cohort will have three subcohorts: (1) patients with other disorders who are receiving DMT used in MS and are experiencing similar side effects (e.g. progressive multifocal encephalopathy (PML) in patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA)), (2) patients who are receiving DMT not used in MS but in whom MS-like illness is suspected (e.g. TNF-alpha inhibitors in patients with rheumatological diseases) and (3) patients with neurodegenerative diseases that may share pathophysiological processes with MS patients (e.g. oxidative stress in patients with Parkinson s disease or mitochondrial dysfunction in patients with mitochondrial diseases) and who do not qualify for the enrollment to the 09-N-0032 protocol. Enrollment of patients with different diseases who are experiencing identical side effects on DMTs as those studied in MS cohort will help to answer the question of whether the identified mechanism of action of the side effect is MS specific or generalizable. The other neurological disease cohort will provide data to assess the specificity of the MRI findings in the MS cohort.

Study Type : Observational
Estimated Enrollment : 1500 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Evaluation of Progression in Multiple Sclerosis by Magnetic Resonance Imaging (MRI)
Study Start Date : March 13, 1989

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Level of disease activity on MRI, defined as the volume of new lesions on T2-weighted MRI since the baseline

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.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion criteria for all populations:

  • Diagnosis of MS based on combined MRI and clinical criteria (Polman et al., 2005) OR presentation with a clinically isolated syndrome consistent with MS and at least two abnormalities on MRI consistent with MS OR diagnosis of another neurological disease of the CNS (see Section 6.1.2) OR patients with other diseases who are receiving identical DMTs as the MS cohort OR patients who acquire an MS-like disease while receiving immunomodulatory agents for a different indication.
  • For patients with neuroimmunological disorders, treatment with any available immunomodulatory therapy.
  • Age greater than or equal to 18.
  • Able to give informed consent.


Exclusion criteria for all cohorts:

  • Contraindication to MRI.
  • Fulfills inclusion criteria for 09-N-0032 protocol, i.e. any untreated neuroimmunological or CNS white matter disease that requires diagnostic work-up.
  • Pregnancy.
  • Unwilling to allow coded samples to be processed offsite or unwilling to have coded samples used in other studies.

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): NCT00001248

Contact: Joan M Ohayon, C.R.N.P. (301) 496-3825
Contact: Daniel S Reich, M.D. (301) 496-1801

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)
Principal Investigator: Daniel S Reich, M.D. National Institutes of Health Clinical Center (CC)

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS) Identifier: NCT00001248     History of Changes
Other Study ID Numbers: 890045
First Posted: November 4, 1999    Key Record Dates
Last Update Posted: December 6, 2018
Last Verified: July 2, 2018

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Multiple Sclerosis
MRI (Magnetic Resonance Imaging)

Additional relevant MeSH terms:
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases