Fingolimod in Schizophrenia Patients
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Fingolimod; placebo
Intervention description: 0.5mg each day of 8 week cycle; 1 tablet each day of 8 week cycle
Intervention MeSH terms: Fingolimod Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: psychosis; schizophrenia; cognition; fingolimod

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.
    

Eligibility criteria:

        Inclusion

          -  18 to 65 yrs, able to give informed consent

          -  DSM IV-TR Diagnosis of schizophrenia or schizoaffective disorder

          -  Previous and/or current exposure to one of the following antipsychotic medications
             (clozapine, olanzapine, risperidone, paliperidone, haloperidol, quetiapine) as defined
             by a minimum of 8 weeks in duration greater than or equal to the Food and Drug
             Administration (FDA) approved therapeutic range for schizophrenia at the time of study
             entry OR previous and/or current exposure to two antipsychotic medications as defined
             by a minimum of 4 weeks in duration and greater than or equal to the FDA approved
             therapeutic range for schizophrenia at the time of study entry

          -  willing to participate in a minimum of 1 day of hospitalization

          -  Clinical stability:

               1. CGI-S score of < 4 at randomization AND

               2. no exacerbation of illness within 4 weeks prior to randomization, leading to an
                  intensification of psychiatric care in the opinion of the investigator AND

               3. antipsychotic treatment stability for at least 4 weeks prior to randomization

          -  Female subjects of childbearing potential must test negative for pregnancy at
             screening and agree to use a single, effective, medically acceptable method of birth
             control for the duration of the study and for two months following cessation of study
             medication

          -  Subjects must agree not to consume tonic water for the duration of the study and for
             two months following cessation of study medication

          -  Sub-optimally treated positive OR negative symptoms as defined by the Brief
             Psychiatric Rating Scale (BPRS):

               1. BPRS positive symptom factor (conceptual disorganization, hallucinations,
                  suspiciousness, unusual thought content) score of > 4 on any one item or a sum >
                  8 on the factor

               2. BPRS negative symptom factor (motor retardation, blunted affect, inappropriate
                  affect) score of > 4 on any one item or a sum > 6 on the factor

        Exclusion

          -  Subjects who are considered prisoners per the IU Standard Operating Procedures for
             Research Involving Human Subjects

          -  Current acute, serious, or unstable medical conditions

          -  Clinically significant electrocardiogram abnormality: corrected QT interval >450 msec
             (M) or >470 msec (F) prior to randomization OR sinus bradycardia (HR < 50 beats/min)

          -  Subjects who have experienced the following within the six months prior to study
             entry: myocardial infarction, unstable angina, stroke, transient ischemic attach
             (TIA), decompensated heart failure requiring hospitalization or Class III/IV heart
             failure

          -  Hypokalemia, hypomagnesemia, or congenital long-QT syndrome

          -  Known HIV+ status

          -  Active seizure disorder

          -  Pregnant or lactating women or women who plan to become pregnant or will be lactating
             within two months after cessation of study drug

          -  Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS
             unit, ventriculoperitoneal shunt, or other contraindication to undergoing an MRI scan

          -  Class1a or class 3 antiarrhythmic agents, beta blockers, diltiazem, verapamil,
             digoxin, tricyclic antidepressants, warfarin, ketoconazole, ketamine

          -  Subjects likely to need a live attenuated vaccine during the course of the study or
             within two months after stopping study medication

          -  Subjects with no history of chicken pox or chicken pox vaccination, or with a negative
             VZV titer

          -  Active herpes simplex outbreak, mononucleosis, or zoster

          -  Subjects with histories of ischemic heart disease, myocardial infarction, congestive
             heart failure, cardiac arrest, cerebrovascular disease, unexplained or recurrent
             syncope, cardiac conduction prolongations (prolonged P-R interval), cardiac
             arrhythmias, symptomatic bradycardia, or severe untreated sleep apnea

          -  Antineoplastic, immunosuppressive, or immune modulating therapies

          -  History of macular edema or uveitis

          -  Known IQ < 70

          -  Current active fungal or viral infection

          -  Current DSM IV-TR diagnosis of substance dependence (excluding caffeine and nicotine)

          -  Positive urine toxicology screen for the following: cocaine, barbiturates,
             methamphetamine, opiate, methadone, phencyclidine, or amphetamine prior to
             randomization

          -  Test positive for (1) Hep C virus antibody, (2) Hep B surface antigen (HBsAg) with or
             without positive Hep B core total antibody, (3) HIV 1 or 2 antibodies, or (4) Mantoux
             tuberculin test.

          -  Moderate to severe renal impairment as defined by creatinine clearance < 60 ml/min at
             screening

          -  Hepatic impairment as defined by liver transaminases or total bilirubin > 3 × upper
             limit of normal

          -  Subjects considered a high risk for suicidal acts - active suicidal ideation OR any
             suicide attempt in 90 days prior to screening

          -  Subjects who have participated in a clinical trial with any pharmacological treatment
             intervention for which they received study-related medication in the 4 weeks prior to
             screening OR Subjects currently receiving treatment (within 1 dosing interval + 4
             weeks) with an investigational depot formulation of an antipsychotic medication

          -  Subjects who demonstrate overtly aggressive behavior or who are deemed to pose a
             homicidal risk in the investigator's opinion