Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia

Study Overview
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Brief Summary
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This a randomized double-blind placebo controlled trial which aims to determine the beneficial effects of minocycline augmentation to clozapine in partial responders to Treatment Resistant Schizophrenia (TRS).

Detailed Description
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The primary objective is to determine if the addition of minocycline to Clozapine, Treatment as Usual (TAU) Improves negative symptoms and/or positive symptoms. The secondary objectives are to determine: Effects on cognitive functioning. Effects on social functioning and quality of life. Safety and tolerability. Possible additive effects of Minocycline added to TAU The effect on inflammatory biomarkers associated with schizophrenia. Both pro and anti-inflammatory cytokines will be drawn at baseline and endpoint. We will test to see if minocycline is associated with improvements in abnormal cytokines as compared to placebo. The study will be a randomized double-blind placebo controlled trial of minocycline added to clozapine (Treatment as Usual) in TRS. There will be two treatment arms: one arm receiving TAU with minocycline and the other TAU with placebo for a period of twelve weeks.

Official Title
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Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia: A Randomised Placebo-controlled Double-blind Trial

Conditions
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Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder

Intervention / Treatment
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* Drug: Minocycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged between 18-65 years, IQ >70 (to complete assessments) identified by treating psychiatrist. Confirmation of schizophrenia by using The MINI psychiatric interview (at baseline only) Assessed as competent to provide informed consent by treating psychiatrist. Antipsychotic medication has remained stable 4 weeks prior to baseline *. Assessed as a partial responder to clozapine: patients prescribed clozapine at a stable therapeutic dose for a minimum of 3 months with total Positive and Negative Syndrome Schizophrenia (PANSS) score >70. Exclusion Criteria: Prior history of intolerance or serious side effects (hepatotoxicity, photosensitivity, blood dyscrasias) to any of the Tetracyclines. Concomitant Penicillin therapy or concomitant anticoagulant therapy. Active substance abuse (except nicotine or caffeine) or dependence within the last three months according to ICD 10 criteria. Treatment with Warfarin or Lamotrigine. Current or previous treatment with minocycline or other tetracycline antibiotics in the preceding three months before study entry. Relevant current or past hematologic, hepatic, renal, neurological or other medical disorder that in the opinion of the principal investigator may interfere with the study. Pregnant or breast-feeding females

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>Matching placebo for Minocycline | Drug: Minocycline<br>* Minocycline 200mg per day<br>* Other names: Mesodrum;|
| Experimental: Minocycline<br>Minocycline 200mg once a day orally | Drug: Minocycline<br>* Minocycline 200mg per day<br>* Other names: Mesodrum;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale PANSS | PANSS is an assessment measures to assess severity of symptoms of schizophrenia | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CogState | Measuring all seven domains recommended by MATRICS (NIMH initiative). These domains include speed processing, attention/vigilance, Working memory (nonverbal & verbal), verbal learning, visual learning, reasoning and problem solving and social cognition's. | 3 Month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Anti-inflammatory, Clozapine, Minocycline, Psychosis NOS