Evaluation of Mirtazapine and Folic Acid for Schizophrenia:

Study Overview
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Brief Summary
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Multicentre randomised double-blind, placebo-controlled 2x2 factorial trial investigating the effects of adding mirtazapine and folic acid to existing therapy for patients with schizophrenia

Detailed Description
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The combination of mirtazapine plus antipsychotic potentially offers considerable benefit for patients with schizophrenia. Folic acid is a promising adjunctive therapy for schizophrenia that may also provide benefits for patients with other mental disorders. Furthermore the effects of folic acid may be affected by genotype. The trial will investigate the effects of adding mirtazapine and the effects of adding folic acid to treatments for schizophrenia. At randomisation, patients will be separately randomised to mirtazapine or placebo and to folic acid or placebo. Randomised, double-blind, placebo-controlled 2x2 factorial trial with 12-week follow-up.

Official Title
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Multicentre Randomised Double-blind, Placebo-controlled 2x2 Factorial Trial Investigating the Effects of Adding Mirtazapine and Folic Acid to Existing Therapy for Patients With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: mirtazapine
* Drug: folic acid placebo
* Drug: mirtazapine placebo
* Drug: folic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inpatients or outpatients age 18 to 70 years; Meet DSM-IV criteria for schizophrenia; Signed an informed consent form by patients or their legally acceptable representatives; PANSS total score >=60 and at least one item of P1, P2, P3, P5 or P6 >=4 to ensure subject has current active psychotic symptoms - i.e. hallucinations, delusions, thought disorder; Subjects who are currently taking effective dose of antipsychotic; Women must agree to practice an effective method of birth control if they are sexually active before entry and throughout the study. Exclusion Criteria: Meet any other DSM-IV Axis I disorders; Meet DSM-IV criteria for substance abuse or dependence; Have been treatment-resistant to 2 or more kinds of antipsychotics with sufficient dosage for at least 4 weeks, or require clozapine treatment, or have received clozapine treatment within 1 month prior to randomization; Subjects are actively suicidal or judged clinically to be at risk of serious suicidal or violent behavior in the opinion of the investigator; Have serious or unstable medical illness (e.g., cardiovascular disease, neurologic, hematologic, renal, hepatic, immunologic, endocrine, or other systemic illness), or have any clinically significant abnormality on laboratory test or ECG which indicate severe medical conditions; Have received electroconvulsive therapy within 28 days before randomization; Have received long acting antipsychotic within 1 treatment cycle before randomization; Have received antidepressant within 14 days, or have received MAOIs within 4 weeks before randomization or require antidepressive treatment; History of prostatic hypertrophy or dysuria; History of narrow-angle glaucoma or elevation of intraocular pressure; Known or suspected history of allergy or have contradiction to mirtazapine or folic acid; Known have currently requirement of taking mirtazapine or folic acid; Women who are pregnant or nursing; Have previously completed or withdrawn from this study, or participated in a clinical trial of another drug within 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: mirtazapine+folic acid<br>mirtazapine 30mg QD, folic acid 0.4mg QD | Drug: mirtazapine<br>* mirtazapine 30mg QD<br>* Other names: Remeron;Drug: folic acid<br>* folic acid 0.4mg QD<br>* Other names: vitamin B 9;|
| Active Comparator: mirtazapine+folic acid placebo<br>mirtazapine 30mg QD, folic acid placebo 1 tablet QD | Drug: mirtazapine<br>* mirtazapine 30mg QD<br>* Other names: Remeron;Drug: folic acid placebo<br>* folic acid placebo 1 tablet QD<br>* Other names: Folic placebo;|
| Active Comparator: mirtazapine placebo+folic acid<br>mirtazapine placebo 1 tablet QD, folic acid 0.4mg QD | Drug: mirtazapine placebo<br>* mirtazapine placebo 1 tablet QD<br>* Other names: Remeron placebo;Drug: folic acid<br>* folic acid 0.4mg QD<br>* Other names: vitamin B 9;|
| Placebo Comparator: mirtazapine placebo+folic acid placebo<br>mirtazapine placebo 1 tablet QD, folic acid placebo 1 tablet QD | Drug: folic acid placebo<br>* folic acid placebo 1 tablet QD<br>* Other names: Folic placebo;Drug: mirtazapine placebo<br>* mirtazapine placebo 1 tablet QD<br>* Other names: Remeron placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the efficacy of mirtazapine and placebo for treatment of symptoms associated with schizophrenia |  | baseline, week4, week8, week12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the efficacy of folic acid and placebo for treatment of symptoms of schizophrenia |  | baseline, week4, week8, week12 | 
| To compare the efficacy of mirtazapine and placebo for treatment of negative symptoms of schizophrenia |  | baseline, week4, week8, week12 | 
| To compare the efficacy of folic acid and placebo for treatment of negative symptoms of schizophrenia |  | baseline, week4, week8, week12 | 
| To compare the safety and tolerability of mirtazapine and placebo in patients with schizophrenia |  | baseline, week4, week8, week12 | 
| To compare the safety and tolerability of folic acid and placebo in patients with schizophrenia |  | baseline, week4, week8, week12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mirtazapine, folic acid, schizophrenia