fMRI Study of Treatment Recommendations Comparing Recently Diagnosed Multiple Sclerosis (MS) Patients to Controls
Condition: Relapsing-Remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Study type: Observational

Summary: 
      Impaired short term memory, attention and concentration lapses, and slower processing of
      information occur in up to 40-65% of patients with Multiple Sclerosis (MS). The quality of
      life of individuals with MS is impacted to the degree with which they experience these
      symptoms.

      There are several medications approved by the United States Food and Drug Administration
      (FDA) to treat MS symptoms and to modify (slow) disease course. Traditional approaches to
      determining the effectiveness of medications used in treating MS rely on reports of the
      number of relapses an individual experiences, as well as standard clinical tests, such as the
      Kurtzke Expanded Disability Status Scale (EDSS).

      This research study will look at whether the functional magnetic resonance imaging (fMRI)
      scan can be used as a tool for measuring changes in the brain associated with treatment in MS
      patients. Unlike a typical MRI which provides structural information about the brain, the
      fMRI provides information about brain activity during performance of cognitive or motor
      tasks.
    

Detailed description: 
      The development of the immunomodulatory, disease-modifying therapies (DMT) represents a major
      advance for the treatment of multiple sclerosis (MS). To date, immunomodulatory agents
      approved for the treatment of MS in the United States include two forms of recombinant
      interferon-beta (IFN-beta-1a [Avonex, Rebif] and IFN-beta-1b [Betaseron]) and synthetic
      glatiramer acetate [Copaxone]. These drugs have been shown to favorably alter the natural
      history of relapsing remitting MS by slowing the progression of disability, reducing relapse
      rate, and decreasing brain inflammation as measured by MRI. There is evidence that the
      treatment effects of both IFN-beta and glatiramer acetate are related to their properties in
      regulating various components of the immune system, in particular, the T cell functions (e.g.
      proliferation and migratory behavior) and cytokine production.

      Though demonstrating clear efficacy on a number of short-term clinical measures, these agents
      are not cures and most patients with MS continue to experience disease activity in spite of
      treatment. Over the last ten years, clinicians have become comfortable initiating therapy
      with DMT. Now, attention is focused on monitoring the results of a chosen therapy and
      deciding whether or not a patient is responding optimally to treatment. At present, however,
      clinicians lack criteria for defining optimal response to DMT as well as evidence-based
      recommendations on how to improve treatment outcomes for individual patients.

      Using a recently published model generated by an advisory board from the United States, as a
      framework, The Canadian Multiple Sclerosis Working Group (CMSWG) developed practical,
      evidence-based recommendations on how neurologists can assess the status of patients on DMT
      and decide when it may be necessary to modify treatment in order to optimize outcomes. The
      CMSWG's recommendations are based on monitoring relapses, neurological progression and MRI
      activity. These recommendations have yet to be implemented in a prospective, randomized,
      comparative Phase IV clinical trial.

      Traditional measures do not provide critical information about the neural systems that
      underlie change in behavioral performance. The goal of developing a surrogate biological
      marker of drug efficacy is to be able to measure the extent to which a drug reaches its
      intended targeted neural system, and to understand and predict the impact of treatment on
      existing neuropathology. Ideally, relevant clinical outcome measures should be well
      correlated with the biomarker.

      fMRI is a new tool for noninvasive imaging of human brain function. Without the use of
      contrast agents, fMRI detects regional MR signal increases that have been hypothesized to
      reflect decreases in deoxyhemoglobin due to local increases in blood flow/volume during task
      activation. fMRI has higher spatial and temporal resolution than other existing functional
      imaging techniques, making it ideal for the study of complex cognitive functions in patient
      populations.
    

Intervention name(s): IFN-β-1a (Rebif®)
Intervention type(s): Drug
Intervention description(s): 44 mcg Three times a week, subcutaneous injection
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        ProHealth Care, Waukesha Memorial Hospital Neuroscience Center
      
Keywords: Multiple Sclerosis; Disease Modifying Therapy