Evaluation of Mirtazapine and Folic Acid for Schizophrenia: (RECOVERY2)

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

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

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: mirtazapine; Drug: folic acid; Drug: folic acid placebo; Drug: mirtazapine placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 333
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100088
      • Beijing Anding Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Inpatients or outpatients age 18 to 70 years;
2. Meet DSM-IV criteria for schizophrenia;
3. Signed an informed consent form by patients or their legally acceptable representatives;
4. 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;
5. Subjects who are currently taking effective dose of antipsychotic;
6. Women must agree to practice an effective method of birth control if they are sexually active before entry and throughout the study.

Exclusion Criteria:

1. Meet any other DSM-IV Axis I disorders;
2. Meet DSM-IV criteria for substance abuse or dependence;
3. 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;
4. Subjects are actively suicidal or judged clinically to be at risk of serious suicidal or violent behavior in the opinion of the investigator;
5. 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;
6. Have received electroconvulsive therapy within 28 days before randomization;
7. Have received long acting antipsychotic within 1 treatment cycle before randomization;
8. Have received antidepressant within 14 days, or have received MAOIs within 4 weeks before randomization or require antidepressive treatment;
9. History of prostatic hypertrophy or dysuria;
10. History of narrow-angle glaucoma or elevation of intraocular pressure;
11. Known or suspected history of allergy or have contradiction to mirtazapine or folic acid;
12. Known have currently requirement of taking mirtazapine or folic acid;
13. Women who are pregnant or nursing;
14. Have previously completed or withdrawn from this study, or participated in a clinical trial of another drug within 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: mirtazapine+folic acid; mirtazapine 30mg QD, folic acid 0.4mg QD	Drug: mirtazapine; mirtazapine 30mg QD; Other Names: Remeron; Drug: folic acid; folic acid 0.4mg QD; Other Names: vitamin B 9
Active Comparator: mirtazapine+folic acid placebo; mirtazapine 30mg QD, folic acid placebo 1 tablet QD	Drug: mirtazapine; mirtazapine 30mg QD; Other Names: Remeron; Drug: folic acid placebo; folic acid placebo 1 tablet QD; Other Names: Folic placebo
Active Comparator: mirtazapine placebo+folic acid; mirtazapine placebo 1 tablet QD, folic acid 0.4mg QD	Drug: folic acid; folic acid 0.4mg QD; Other Names: vitamin B 9; Drug: mirtazapine placebo; mirtazapine placebo 1 tablet QD; Other Names: Remeron placebo
Placebo Comparator: mirtazapine placebo+folic acid placebo; mirtazapine placebo 1 tablet QD, folic acid placebo 1 tablet QD	Drug: folic acid placebo; folic acid placebo 1 tablet QD; Other Names: Folic placebo; Drug: mirtazapine placebo; mirtazapine placebo 1 tablet QD; Other Names: Remeron placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Capital Medical University
• Investigators: Principal Investigator: Gang Wang, M.D., Beijing Anding Hospital, Capital Medical University

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: December 17, 2010
• First Submitted That Met QC Criteria: December 17, 2010
• First Posted (Estimate): December 20, 2010

Study Record Updates

• Last Update Posted (Estimate): August 2, 2016
• Last Update Submitted That Met QC Criteria: August 1, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: schizophrenia; mirtazapine; folic acid
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Micronutrients; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Vitamins; Hematinics; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Adrenergic alpha-Antagonists; Adrenergic alpha-2 Receptor Antagonists; Folic Acid; Vitamin B Complex; Mirtazapine
• Other Study ID Numbers: RECOVERY2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided