Bethesda, Maryland 20892


Purpose:

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.


Study summary:

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.


Criteria:

- INCLUSION CRITERIA: One of the following: - Diagnosis of MS or clinically isolated syndrome based on combined MRI and clinical criteria - Presentation with neuroimaging features consistent with MS. - Diagnosis of another disease of the CNS - Diagnosis with a non-neurologic disease but receiving DMT typically prescribed for MS. - New onset of an MS-like disease while receiving immunomodulatory agents for a different indication. - Healthy volunteer. - Age greater than or equal to 18. - Able to give informed consent. NIH employees are eligible to participate. EXCLUSION CRITERIA: - Contraindication to MRI. - Pregnancy. - Unwilling to allow coded samples to be processed offsite or unwilling to have coded samples used in other studies.


NCT ID:

NCT00001248


Primary Contact:

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

Joan M Ohayon, C.R.N.P.
Phone: (301) 496-3825
Email: eatonj@ninds.nih.gov


Backup Contact:

Email: reichds@ninds.nih.gov
Daniel S Reich, M.D.
Phone: (301) 496-1801


Location Contact:

Bethesda, Maryland 20892
United States

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
Phone: 800-411-1222
Email: prpl@cc.nih.gov

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: October 09, 2019

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