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

Multiple Sclerosis Clinical Trial

Official title:

Evaluation of Progression in Multiple Sclerosis by Magnetic Resonance Imaging (MRI)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00001248
• Other study ID #: 890045
• Secondary ID: 89-N-0045
• Status: Recruiting
• Start date: July 23, 1992

Study information

• Verified date: February 13, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Jenifer E Dwyer
• Phone: (301) 496-3825
• Email: jenifer.dwyer[@]nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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Description:

Studies performed under 89-N-0045 are primarily designed to examine the evolving natural history of multiple sclerosis (MS) and its mimickers, viewed through the window of neuroimaging (especially magnetic resonance imaging or MRI). The protocol has four other important objectives: (1) Screening prospective participants for selected NINDS Neuroimmunology Clinic 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.

To the extent possible, scheduled testing performed under this protocol will coincide with standard-of-care evaluations for diagnosis and longitudinal clinical management, thereby reducing the burden of research participation by participants. Such testing may involve state-of-the-art research methods. Additional pure-research visits may be scheduled to further investigate findings observed on scheduled visits and/or outside studies.

Disease activity on MRI will be assessed using several MRI measures, including the detection of new on-study lesions, quantification of contrast-enhancing lesions, the total number and/or volume of MRI-visible lesions, brain volume and brain volume change, and more advanced MRI measures of tissue damage, such as quantitative magnetic relaxation mapping, diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI), and MR spectroscopy (MRS). Participants may be assessed with other imaging modalities, including optical coherence tomography (OCT), and they will be asked to provide research samples (generally blood, but also saliva and cerebrospinal fluid) and be studied clinically.

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 include patients with other CNS diseases that may share pathophysiological processes with MS patients (e.g. other inflammatory conditions of the central nervous system, mitochondrial disorders, leukodystrophies, neurodegenerative diseases that may cause axonal loss or oxidative stress, or cerebral small vessel disease). Enrollment of these control patient populations will help to answer the question of whether the identified MRI findings and/or pathophysiological mechanisms are MS-specific or generalizable.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3750
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

• INCLUSION CRITERIA:

• One of the following:

• Diagnosis of MS or clinically isolated syndrome based on currently accepted diagnostic criteria.

• Presentation with neuroimaging features consistent with MS.

• Diagnosis of another disease of the CNS

• 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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Calabresi PA, Stone LA, Bash CN, Frank JA, McFarland HF. Interferon beta results in immediate reduction of contrast-enhanced MRI lesions in multiple sclerosis patients followed by weekly MRI. Neurology. 1997 May;48(5):1446-8. doi: 10.1212/wnl.48.5.1446. — View Citation

Calabresi PA, Tranquill LR, Dambrosia JM, Stone LA, Maloni H, Bash CN, Frank JA, McFarland HF. Increases in soluble VCAM-1 correlate with a decrease in MRI lesions in multiple sclerosis treated with interferon beta-1b. Ann Neurol. 1997 May;41(5):669-74. doi: 10.1002/ana.410410517. — View Citation

Tresley RM, Stone LA, Fields N, Maloni H, McFarland H, Frank JA. Clinical safety of serial monthly administrations of gadopentetate dimeglumine in patients with multiple sclerosis: implications for natural history and early-phase treatment trials. Neurology. 1997 Apr;48(4):832-5. doi: 10.1212/wnl.48.4.832. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the rate of change in the number of new white matter lesions per participant	The primary outcome, which is designed to determine how MS disease activity has changed with the advent of ever-more-effective disease-modifying therapy, is the rate of change in the number of new white matter lesions per participant, indexed by the date of baseline evaluation.	baseline vs. follow up visits

External Links

•   NIH Clinical Center Detailed Web Page