Effects of Gilenya (Fingolimod) on Thalamus Pathology and Cognitive Impairment in Patients With Relapsing Forms of Multiple Sclerosis
Condition: Multiple Sclerosis; Healthy
MeSH terms: Multiple Sclerosis; Sclerosis; Cognitive Dysfunction
Study type: Observational

Summary: 
      This study aims to assess the effect of Gilenya on brain pathology and cognitive impairment
      over 6, 12, and 24 months in patients with relapsing MS using MRI, clinical data, and
      neurological assessments. Healthy controls will also be followed over 6, 12, and 24 months
      using the same measures.
    

Detailed description: 
      This is an open-label, single-blinded, observational, prospective, 24 months follow-up,
      controlled study to assess the efficacy of Gilenya on thalamus pathology and cognitive
      impairment in 30 relapsing MS patients naïve to Gilenya who fulfilled the inclusion and
      exclusion criteria used for screening and started Gilenya, on a clinical basis. In addition,
      20 HCs will be included as a reference population. Because this is an observational study
      investigating evolution of thalamic atrophy, iron deposition, cognitive dysfunction and
      response to herpes viruses in patients treated with Gilenya on a clinical basis the patients
      are not starting Gilenya as an investigational drug. Therefore, the patients who are already
      started Gilenya by the treatment decision of their physician will be asked to participate in
      this observational study.

      The screening and starting procedures criteria for Gilenya on a clinical basis and for our
      study are defined by the Gilenya PI. All patients in our clinic have standardized assessments
      before starting any disease-modifying therapy. Once the patient decided to start Gielnya on a
      clinical basis and qualified on a screening, as defined by Gilenya PI, our team will be
      informed and contact the patient regarding participation in the present study before
      receiving first dose of Gilenya. Once the informed consent is signed, the patient will follow
      study procedures, as outlined in the protocol and study evaluation schedule. All subjects
      will be assessed at 0, 6, 12 and 24 months with the same clinical, 3T MRI and laboratory, and
      humoral response to herpes viruses examinations. The cognitive assessments and evaluation of
      environmental risk factors will be performed at 0, 12 and 24 months. Safety will be also
      assessed at 0, 6, 12 and 24 months of the study.

      The healthy controls (HC) will serve as reference comparison group to patients for atrophy
      iron, cognitive and response to herpesvirus outcomes. We considered alternative study designs
      as listed below. The head-to-head comparison with untreated or comparator-treated patients
      are difficult to conduct and can not be performed without proper randomization and
      double-blinding which is costly and unfeasible in mechanistical study like is the one
      proposed. The inclusion of a HC group provides a valuable baseline, allowing evaluation of
      the proposed techniques for normal variation between individuals, against which changes in
      the proposed outcomes could be compared. Use of HCs for comparison with a patient population
      in prospective longitudinal pilot studies of non-conventional MRI, including measurement of
      thalamic atrophy and iron deposition, may become an attractive approach in the future for
      several reasons. First, the ultimate goal of therapy is to normalize patient changes over
      time, to those observed in HCs over the same time period. HCs also experience brain changes
      over time and so the notion of arresting disease progression as measured by proposed outcomes
      requires validation by reference to a comparator without disease progression to account for
      age-related changes. Second, ethical considerations preclude placebo-controlled studies using
      an established MS treatment versus placebo-treatment in patients with RRMS.

      The MRI analysis will be performed fully blinded, as are all phase I, II, III and IV trials
      calculated at the Buffalo Neuroimaging Analysis Center (BNAC), Buffalo, NY. BNAC has been
      involved as an centralized MRI reading center in many MS clinical trials that included over
      500 sites around the world in 55 countries The detailed procedures of how the MRI DICOM files
      are blinded and how the workload is distributed are part of our internal standard operating
      procedures (SOPs) that have been accepted as appropriate following standard audits by
      government and industry agencies.

      All participants will undergo study eligibility screening and consenting by a Clinical
      Research Project Coordinator. The participant will be provided with a description of the
      required testing for study participation, and any risks will be described in order for the
      person to make an informed decision regarding voluntary study participation. This is also an
      opportunity for the person to ask questions regarding the study and the testing components.
      All study participants who choose to enroll in the study will be asked to sign and date the
      consent form in front of the Study Coordinator who will also sign and date the consent as
      witness.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        30 relapsing MS patients naïve to Gilenya who fulfill the inclusion and exclusion criteria
        used for screening and start Gilenya, on a clinical basis will be enrolled in the study. In
        addition, 20 healthy controls will be included as a reference population. The plan is to
        recruit the 50 subjects (30 relapsing MS and 20 healthy controls) at a single center.
      
Biospecimen description: 
      Whole blood
    
Keywords: Multiple sclerosis; Gilenya; Healthy controls; Thalamic atrophy; MRI