Schizophrenia Clinical Trial
— STEPOfficial title:
Safety and Efficacy of Fingolimod in Schizophrenia Patients Who Have Suboptimal Responses to Antipsychotic Drug Treatment
NCT number | NCT01779700 |
Other study ID # | 11T-001 |
Secondary ID | |
Status | Completed |
Phase | Phase 2 |
First received | |
Last updated | |
Start date | January 2013 |
Est. completion date | August 2016 |
Verified date | March 2019 |
Source | Indiana University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 40 |
Est. completion date | August 2016 |
Est. primary completion date | August 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility |
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 |
Country | Name | City | State |
---|---|---|---|
United States | Center for NeuroImaging | Indianapolis | Indiana |
United States | Larue D Carter Memorial Hospital | Indianapolis | Indiana |
United States | Prevention and Recovery Center | Indianapolis | Indiana |
Lead Sponsor | Collaborator |
---|---|
Indiana University |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | QTcB Change | To determine the safety of fingolimod, as measured by the electrocardiogram (ECG) QT interval corrected by Bazett's (QTcB) value. | Screening, Day 0, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56, Day 84, Day 112 | |
Primary | Levels of Lymphocyte | To determine the safety of fingolimod, as measured by the absolute lymphocyte count | Baseline, 4 weeks, 8 weeks | |
Primary | Symptom Changes - PANSS Total Score | The Positive and Negative Syndrome Scale (PANSS) is a semi-structured interview, containing 30 items that assess symptoms of psychotic disorders including positive, negative, and general psychopathology symptoms. Positive symptoms are rated on 7 items, negative symptoms are rated on 7 items, and general psychopathology on 16 items. Scores for each item range from 1=absent to 7=extreme. Positive, negative, and general psychopathology symptoms can each respectively render total scores. Positive total scores ranging from 7-49, negative total scores ranging from 7-49, and general psychopathology scores ranging from 16-112. When all items are summed together a total score is generated. Total scores for all items range from 30-210, a lower score reflecting fewer symptoms. | Baseline, 4 weeks, 8 weeks | |
Secondary | Verbal Memory - BACS | The Brief Assessment of Cognition in Schizophrenia (BACS) is a battery specifically designed to measure treatment-related changes in cognition. The BACS utilizes 6 tasks, and has alternate forms, thus minimizing practice effects. Each task generates a raw score (with a higher score indicating better performance): verbal memory 0-75; digit sequencing 0-28; token motor task 0-100; semantic&letter fluency 0-148; symbol coding 0-110; and tower of London 0-22. The raw scores are used to generate a composite score that is calculated by summing t-scores derived by comparisons with a normative sample of 404 healthy controls. The six brief assessments' t-scores, are summed, and averaged to provide a composite t-score. The composite score min and max are between -43 and 100. A higher score indicating better cognitive performance. | Baseline, 4 weeks, 8 weeks | |
Secondary | Cognition Change - BACS | The Brief Assessment of Cognition in Schizophrenia (BACS) is a battery specifically designed to measure treatment-related changes in cognition by utilizing 6 tasks, and has alternate forms, thus minimizing practice effects. Each task generates a raw score (with a higher score indicating better performance): verbal memory 0-75; digit sequencing 0-28; token motor task 0-100; semantic&letter fluency 0-148; symbol coding 0-110; and tower of London 0-22. The raw scores are used to generate a composite score that is calculated by summing t-scores derived by comparisons with a normative sample of 404 healthy controls. The six brief assessments' t-scores, are summed, and averaged to provide a composite t-score. The composite score min and max are between -43 and 100. A higher score indicating better cognitive performance. | Baseline, 4 weeks, 8 weeks | |
Secondary | Cognition Change - Trails B | The Trail Making Test-Part B (Trails B) is a measure of visual attention and task switching. The task requires a subject to 'connect-the-dots' of 25 consecutive targets on a sheet of paper. In Part B version the subject alternates between numbers and letters (1, A, 2, B, etc.) The goal of the test is for the subject is to finish part B as quickly as possible, the time taken to complete the test is used as the primary performance metric. The score is the number of seconds it took to complete the test. | Baseline, 4 weeks, 8 weeks | |
Secondary | Positive Symptom Change - PANSS | The Positive and Negative Syndrome Scale (PANSS) is a semi-structured interview, containing 30 items that assess symptoms of psychotic disorders including positive, negative, and general psychopathology symptoms. Positive symptoms are rated on 7 items, negative symptoms are rated on 7 items, and general psychopathology on 16 items. Scores for each item range from 1=absent to 7=extreme. Positive, negative, and general psychopathology symptoms can each respectively render total scores. Positive total scores ranging from 7-49, negative total scores ranging from 7-49, and general psychopathology scores ranging from 16-112. When all items are summed together a total score is generated. Total scores for all items range from 30-210, a lower score reflecting fewer symptoms. | Baseline, 4 weeks, 8 weeks | |
Secondary | Negative Symptom Change - PANSS | The Positive and Negative Syndrome Scale (PANSS) is a semi-structured interview, containing 30 items that assess symptoms of psychotic disorders including positive, negative, and general psychopathology symptoms. Positive symptoms are rated on 7 items, negative symptoms are rated on 7 items, and general psychopathology on 16 items. Scores for each item range from 1=absent to 7=extreme. Positive, negative, and general psychopathology symptoms can each respectively render total scores. Positive total scores ranging from 7-49, negative total scores ranging from 7-49, and general psychopathology scores ranging from 16-112. When all items are summed together a total score is generated. Total scores for all items range from 30-210, a lower score reflecting fewer symptoms. | Baseline, 4 weeks, 8 weeks | |
Secondary | Plasma Cytokines Levels - IL-10 | To assess IL-10 plasma cytokines levels changes in participants taking fingolimod versus placebo | Baseline, 4 weeks, 8 weeks | |
Secondary | Plasma Cytokines Levels - IL-17A | To assess IL-17A plasma cytokines levels changes in participants taking fingolimod versus placebo | Baseline, 4 weeks, 8 weeks | |
Secondary | Plasma Cytokines Levels - IL-1BETA | To assess IL-1BETA plasma cytokines levels changes in participants taking fingolimod versus placebo | Baseline, 4 weeks, 8 weeks | |
Secondary | Plasma Cytokines Levels - IL-2 | To assess IL-2 plasma cytokines levels changes in participants taking fingolimod versus placebo | Baseline, 4 weeks, 8 weeks | |
Secondary | Plasma Cytokines Levels - IL-4 | To assess IL-4 plasma cytokines levels changes in participants taking fingolimod versus placebo | Baseline, 4 weeks, 8 weeks | |
Secondary | Plasma Cytokines Levels - IL-6 | To assess IL-6 plasma cytokines levels changes in participants taking fingolimod versus placebo | Baseline, 4 weeks, 8 weeks | |
Secondary | Plasma Cytokines Levels - IL-8 | To assess IL-8 plasma cytokines levels changes in participants taking fingolimod versus placebo | Baseline, 4 weeks, 8 weeks | |
Secondary | Plasma Cytokines Levels - TNFa | To assess TNFa plasma cytokines levels changes in participants taking fingolimod versus placebo | Baseline, 4 weeks, 8 weeks | |
Secondary | Plasma Cytokines Levels - IFNgamma | To assess IFNgamma plasma cytokines levels changes in participants taking fingolimod versus placebo | Baseline, 4 weeks, 8 weeks |
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