- Magnetic resonance imaging (MRI) has been used for decades to help diagnose and monitor
neurological disorders like multiple sclerosis (MS). Researchers want to improve how MRI
pictures are taken. They also want to learn more about using newer MRIs with stronger magnets
to get better pictures than standard MRIs provide.
- To collect data that will help researchers better understand MS and related diseases.
- Adults 18 and older with MS or MRI findings that appear similar to MS, or with other
neurological diseases that may look or act like MS.
- Healthy adult volunteers.
- Participants will be screened with a review of their medical records.
- Participants will have a baseline visit. It will include a physical exam, medical
history, and neurological exam. They may have blood tests.
- The study will last indefinitely.
- Participants may have MRIs. Some MRIs may include a contrast dye. For this, a needle
will be used to guide a thin plastic tube into an arm vein.
- Participants may have up to 2 lumbar punctures per year. Skin will be numbed and a
needle inserted between back bones will remove fluid.
- Participants may give saliva samples and have an eye exam.
- Participants may have evoked potential tests. These measure how the nervous system
responds to different types of stimulation. Participants may sit in front of a TV and
watch pictures on the screen. Or they may wear earphones that make a clicking noise or
static. Or they may get a small electrical shock that may tingle and cause a hand or
- Participants may have tests of strength, spasticity, sensations, balance, and/or
The goals of this protocol are to study the pathophysiology of multiple sclerosis (MS),
primarily through small studies that utilize magnetic resonance imaging (MRI), and to
correlate the results with clinical and biological measures. The protocol includes only
techniques with minimal risk (standard and quantitative clinical evaluation, MRI, blood
draws, saliva testing, urine and stool collection, lumbar punctures, visual evoked
potentials, ophthalmologic evaluation) or more-than-minimal risk (injection of approved
gadolinium-based contrast agents) that are appropriate and common in this study population.
Under this protocol, we will conduct:
- Pilot substudies. These studies are exploratory and hypothesis generating. Once
sufficient data are collected to justify a hypothesis-driven study and a formal power
analysis, further work will continue under either a dedicated protocol or, if
appropriate, a hypothesis-testing substudy. There are no enrollment limitations for
- Hypothesis-testing substudy. These studies have a specific hypothesis that can be tested
with at most 6 participants per arm. If additional participants are required, the
Principal Investigator (PI) and Protocol Review Committee (PIRC) will decide together
whether to continue the hypothesis-testing substudy with more participants without an
amendment, or to file an amendment or new protocol. A memo requesting a review of a
hypothesis-testing substudy for possible additional enrollment will be sent to PIRC and
its statistical reviewer.
The memo will also be forwarded to the IRB.
- Individual patient substudies. These studies seek to increase knowledge of a disease
process or to assist in the diagnosis of an individual patient.
- Technique development substudies. These studies will lay the groundwork for new
experimental paradigms, using the methods approved under this protocol, which can be
further tested in the substudies listed above.
- Training of investigators. These studies will be done to train new investigators in
techniques relevant to the studies under this protocol.
Three groups of study participants will be enrolled:
- MS patients. Participants with definite, probable, or possible MS.
- Patient controls. Participants with diseases that share features with MS.
- Healthy volunteers.
We will design small substudies as ideas arise in the course of our work that are pertinent
to the theme of the pathophysiology of MS (or of diseases that share features with MS). If a
hypothesis testing sub-study leads to results of interest and if a larger population is
necessary to reach statistical significance, a separate protocol will be submitted with a
priori hypotheses, specific study design and power analysis adapted from the pilot or
exploratory substudies performed in the present protocol.
These will include MRI, clinical, and biological outcome measures consistent with the
objectives of the study and its investigators. Imaging measures will focus on features
related to the central nervous system (CNS), particularly focal lesions. Clinical measures
will include standard and established MS disability scales as well as quantitative measures
related to function. Biological measures will include genotype, gene expression, proteomics,
virological studies, and immunological profiling.
- INCLUSION CRITERIA:
- One or more of the following:
- Diagnosis of MS, clinically isolated syndrome, or radiologically isolated
- Presentation with clinical or neuroimaging findings that, in the best judgment of
the investigators, are possibly consistent with central nervous system
- Healthy volunteer.
- Age greater than or equal to18.
- Able to participate in study procedures and provide high-quality clinical research
data, in the best judgment of the investigators.
- Interest of the study investigators in performing one or more procedures under one or
more of the substudies.
- Unwilling to allow sharing and/or use in future studies of coded samples and data that
are collected for this study.
- Inability to provide informed consent.