Gilenya's Impact on Cognitive Function and Thalamic Volumes
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional

Summary: 
      This evaluation will be a one-year feasibility study to characterize the neuroprotective
      benefits of Gilenya and its effects on cognition and grey matter volumes. The study will
      enroll 15 patients with relapsing-remitting multiple sclerosis being treated with Gilenya and
      5 healthy controls. Each participant will undergo a battery of neurometric testing at
      baseline, six months, and one year. In addition, patients will undergo high-field 7T MRI at
      the same time points.
    

Detailed description: 
      Cognitive impairment is a well-recognized manifestation of multiple sclerosis (MS) with
      prevalence estimates ranging from 43 to 70%. It is also known to occur as early as the first
      demyelinating event and is a major factor contributing to quality of life in MS. Treatment
      strategies for cognitive impairment in MS are limited. Several agents have been tested as
      therapeutics for MS-related cognitive dysfunction and have showed no major benefit. Cognitive
      rehabilitation has shown some promise, but the data are limited and many studies have
      suffered from methodological shortcomings. Given the lack of well-established treatment
      options and the substantial impact of cognitive impairment, protection of cognitive function
      from the earliest stages of the disease is of great importance.

      Cognitive outcomes received relatively little attention in the pivotal studies of MS disease
      modifying therapies (DMT), but some data suggest that DMT may have a positive impact on
      cognition. Gilenya is of special interest because it was found to have a significant
      protective effect on whole brain atrophy when compared against placebo and intramuscular
      interferon β-1a in two phase III studies, showing a 31-35% reduction in percentage brain
      volume change. Gilenya's effect on whole brain atrophy leads to the natural hypothesis that
      it may have a beneficial effect on cognitive function in MS. Also of particular interest is
      the extent to which protection of the thalamus and cortex contributes to Gilenya's effect on
      whole brain atrophy and possible effects on cognition.

      The study will enroll 15 subjects from the Cleveland Clinic Mellen Center patient population.
      Participants must have been on Gilenya for at least 6 months at the time of study entry. The
      study will involve three assessments: at baseline, six months, and one year. At each time
      point, participants will undergo 7T MRI of the brain with and without contrast. Participants
      will also undergo a battery of neurometric testing at each time point. The tests will include
      the Brief Visuospatial Memory Test - Revised (visuospatial skills), the iPadTM Processing
      Speed Test (processing speed), the Selective Reminding Test (verbal learning and memory), and
      the Delis-Kaplan Executive Function System Sorting Test (problem-solving skills; can only be
      administered at baseline and one year due to version limitations).
    

Intervention name(s): 7T MRI; Neurocognitive testing
Intervention type(s): Diagnostic Test; Diagnostic Test
Intervention description(s): A high field MRI that will take approximately one hour.; A series of tests to assess memory, verbal skills, and visuospatial skills.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: There will be two groups running in parallel. One will be MS patients (15) and the other will be control patients (5). Both groups will receive the same interventions.
Masking: None (Open Label)
Primary purpose: Other
Keywords: multiple sclerosis; thalamus; high field MRI; cognition