Fingolimod in Schizophrenia Patients
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 2

Summary: 
      This will be a single site safety and proof of concept study conducted at the Indiana
      University Psychotic Disorders Program. Forty subjects with schizophrenia or schizoaffective
      disorders will be randomized 1:1 to double-blind treatment with fingolimod or matched placebo
      for duration of 8 weeks.
    

Detailed description: 
      Study Design:

      This will be a single site safety and proof of concept study conducted at the Indiana
      University Psychotic Disorders Program. Forty subjects with schizophrenia or schizoaffective
      disorders will be randomized 1:1 to double-blind treatment with fingolimod or matched placebo
      for duration of 8 weeks.

      All subjects will be admitted to the Indiana Clinical and Translational Sciences Institute
      Clinical Research Center (CRC) and remain hospitalized for the first 24 (+/- 2) hours post
      initial dose of study medication. The CRC is located in Indiana University Hospital and has
      24 hour staffing with nurses skilled in conducting Phase 1 and Phase 2 investigational drug
      studies.

      Background and Rationale:

      Schizophrenia is a severe brain disorder that begins during the teenage years and early
      twenties and typically progresses to a life-long chronic illness marked by psychotic
      symptoms, cognitive impairment and poor functioning. A leading hypothesis to account for the
      symptoms and cognitive dysfunction of this disorder is that abnormalities exist in cortical
      circuits, particularly in frontal and temporal areas. An interest in cortical circuitry has
      led to a focus on the integrity of cortical white matter tracts as possibly contributing to
      the pathophysiology of this illness. Indeed, several lines of evidence have supported
      abnormalities in white matter structure and function in schizophrenia. Numerous
      myelin-related genes and their functional expression have been associated with schizophrenia.
      Moreover, quantitative and qualitative abnormalities in prefrontal cortical oligodendrocytes
      have been found in postmortem studies. MRI-determined volumetric reductions in prefrontal
      white matter have been reported in schizophrenia. Advances in MRI technology have enhanced
      the ability to study white matter pathology in vivo. Diffusion tensor imaging (DTI) and
      fractional anisotropy (FA) provides an assessment of the density and integrity of white
      matter tracts. Decreased FA has been reported in many de-myelinating diseases including
      multiple sclerosis (MS), leukodystrophies, and HIV. Numerous studies using DTI have reported
      decrements in FA in schizophrenia with the most consistent abnormalities occurring in frontal
      cortical white matter. Also, FA has been shown to be sensitive to therapeutic drug effects in
      MS which supports DTI-derived FA as an outcome measure in clinical trials of neuroprotective
      agents.

      Fingolimod (FTY720, approved as Gilenya™ ) is a sphingosine-1-phosphate (S1P) receptor
      modulator and recently licensed in the USA and several other countries for relapsing forms of
      multiple sclerosis (MS). It is administered as a once per day oral preparation. In
      registration clinical trials, it had positive effects on brain atrophy, MRI-determined axonal
      lesions and relapse rates. Significant improvement in the mean number of MRI assessed T1
      gadolinium (Gd) enhanced lesions/patient and the percentage of patients free of T1
      Gd-enhanced lesions was observed within 6 months of treatment and there was evidence of
      clinical improvement as early as 2 months after treatment initiation
    

Intervention name(s): Fingolimod; placebo
Intervention type(s): Drug; Drug
Intervention description(s): 0.5mg each day of 8 week cycle; 1 tablet each day of 8 week cycle
Other intervention name(s): gilenya; sugar pill
Intervention MeSH terms: Fingolimod Hydrochloride
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: psychosis; schizophrenia; cognition; fingolimod