Magnetic Resonance Imaging (MRI) to Evaluate Activity of Multiple Sclerosis (MS)
|First Received Date ICMJE||November 3, 1999|
|Last Updated Date||August 8, 2015|
|Start Date ICMJE||March 1989|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Level of disease activity on MRI, defined as the volume of new lesions on T2-weighted MRI since the baseline|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00001248 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Magnetic Resonance Imaging (MRI) to Evaluate Activity of Multiple Sclerosis (MS)|
|Official Title ICMJE||Evaluation of Progression in Multiple Sclerosis by Magnetic Resonance Imaging (MRI)|
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.
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 ICMJE||Observational|
|Study Design ICMJE||Time Perspective: Prospective|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition ICMJE||Multiple Sclerosis|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||920|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Inclusion criteria for all populations:
Exclusion criteria for all cohorts:
|Ages||18 Years and older|
|Accepts Healthy Volunteers||Yes|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00001248|
|Other Study ID Numbers ICMJE||890045, 89-N-0045|
|Has Data Monitoring Committee||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )|
|Study Sponsor ICMJE||National Institute of Neurological Disorders and Stroke (NINDS)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||July 2015|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP