Fingolimod in Schizophrenia Patients (STEP)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Safety and Efficacy of Fingolimod in Schizophrenia Patients Who Have Suboptimal Responses to Antipsychotic Drug Treatment|
- Dosing Safety [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]assess the effects of dosing fingolimod in subjects with schizophrenia who are concomitantly being treated with antipsychotic drugs on ECG and laboratory
- Cognition, including executive functioning, verbal fluency, attention, task switching, and motor speed [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]assessment of the effects of fingolimod versus placebo on cognition measures above as determined by BACS and Trails B scores
- verbal memory [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]assessment of the effects of fingolimod versus placebo on cognition measures above as determined by BACS and Trails B scores as well as encoding and recognition tasks within the MRI protocol
- Positive and Negative Symptoms of Schizophrenia [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]assessment of the effects of fingolimod versus placebo on positive and negative symptoms as determined by the PANSS total score
- plasma cytokines [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]assessment of the effects of fingolimod versus placebo on plasma cytokine levels
- working memory [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]assessment of the effects of fingolimod versus placebo on cognition measures above as determined by BACS and Trails B scores as well as encoding and recognition tasks within the MRI protocol
- DTI-derived FA [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]assessment of the effects of fingolimod versus placebo on DTI-derived FA and other MRI indices
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Fingolimod
0.5mg of fingolimod, oral administration, daily, for 8 weeks.
0.5mg each day of 8 week cycle
Other Name: gilenya
Placebo Comparator: placebo
placebo, oral administration, daily, for 8 weeks.
1 tablet each day of 8 week cycle
Other Name: sugar pill
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01779700
|United States, Indiana|
|Center for NeuroImaging|
|Indianapolis, Indiana, United States, 46202|
|Prevention and Recovery Center|
|Indianapolis, Indiana, United States, 46202|
|Larue D Carter Memorial Hospital|
|Indianapolis, Indiana, United States, 46222|
|Principal Investigator:||Alan Breier, MD||Indiana University|
|Principal Investigator:||Michael Francis, MD||Indiana University|