Enhancing Recovery in Early Schizophrenia

Study Overview
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Brief Summary
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Current antipsychotic treatments of schizophrenia are only partially effective, and their use is often associated with serious side effects. Cannabidiol is a natural counterpart of the psychoactive component of marijuana, delta-9- tetrahydrocannabinol and has no psychotomimetic or addictive properties. In a controlled clinical trial of cannabidiol versus amisulpride in acute paranoid schizophrenia we showed a statistically significant clinical improvement in all symptoms clusters of schizophrenia compared to baseline with either treatment. Cannabidiol displayed a significantly superior side-effect profile in particular regarding prolactin elevation, extrapyramidal symptoms and weight gain. The favorable side-effect profile and potentially novel mechanism of action identify this molecule as a potential antipsychotic. However, long-term safety and efficacy data is still lacking. This study is to evaluate the efficacy and safety of the novel compound cannabidiol in the maintenance treatment of schizophrenia in comparison to placebo as an add-on to an established treatment with either amisulpride, aripiprazole, olanzapine, quetiapine or risperidone, in a 12-months, double-blind, parallel-group, randomized, placebo-controlled clinical trial. Thereby, relevant data on cannabidiol's antipsychotic potential will be gained.

Official Title
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Enhancing Recovery in Early Schizophrenia - a Multi-center, Two-arm, Double-blind, Randomized Phase II Trial Investigating Cannabidiol vs. Placebo as an add-on to an Individualized Antipsychotic Treatment

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Cannabidiol as add-on
* Drug: Placebo as add-on


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent given by the subject DSM-IV-TR diagnosis of schizophrenic psychosis (295.10-30, 295.90) First documented diagnosis of schizophrenia must not be no older than seven years. Patients must receive a stable dose of amisulpride, aripiprazole, olanzapine, quetiapine or risperidone (TAU: treatment as usual) at least 4 weeks prior to inclusion in the study to ensure that the maximal effect of the previous medication has been received. Initial PANSS total score of ≤ 75 at baseline. proper contraception in female patients of childbearing potential body mass index between 18 and 40. Exclusion Criteria: Lack of accountability positive urine drug-screening for illicit drugs at screening (except cannabinoids and benzodiazepines) serious suicidal risk at screening visit other relevant interferences of axis 1 according to diagnostic evaluation (MINI) including residual forms of schizophrenia. other relevant neurological or other medical disorders pregnancy or lactation.

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 |
| --- | --- |
| Experimental: Cannabidiol<br>Cannabidiol as add-on to individualized pharmacological treatment | Drug: Cannabidiol as add-on<br>* Cannabidiol capsules 2x200 mg twice a day as add-on to individualized pharmacological treatment with either amisulpride, aripiprazole, olanzapine, quetiapine or risperidone over 26 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo as add-on to individualized pharmacological treatment | Drug: Placebo as add-on<br>* Placebo capsules 2x200 mg twice a day as add-on to individualized pharmacological treatment with either amisulpride, aripiprazole, olanzapine, quetiapine or risperidone over 26 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause discontinuation |  | within 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in Psychopathology assessed by PANSS | Positive and Negative Syndrome Scale (PANSS) | 6, 9 and 12 month | 
| Improvement in Psychopathology assessed by CGI | Clinical Global Impression (CGI) | 6, 9 and 12 month | 
| Improvement in Psychopathology assessed by BSI-53 | Brief Symptom Inventory (BSI-53) | 6, 9 and 12 month | 
| Improvement in Psychopathology assessed by FROGS | Functional Remission of General Schizophrenia (FROGS) | 6, 9 and 12 month | 
| Changes from baseline in Depression Scale | Calgary Depression Scale for Schizophrenia (CDSS) | 6, 9 and 12 month | 
| Improvement in social and occupational functioning assessed by GAF | Global Assessment of Functioning (GAF) | 6, 9 and 12 month | 
| Improvement in social and occupational functioning assessed by PSP | Personal and Social Performance Scale (PSP) | 6, 9 and 12 month | 
| Improvement in social and occupational functioning assessed by EMA | Ecological Momentary Assessment (EMA) | 6, 9 and 12 month | 
| Improvement in Quality of life assessed by WHOQUOL-Bref | WHO Quality of Life-Bref (WHOQUOL-Bref) | 6, 9 and 12 month | 
| Improvement in Quality of life assessed by LQLP | Lancashire Quality of Life Profile (LQLP) | 6, 9 and 12 month | 
| Changes from baseline in Neurocognition assessed by B-CATS | Brief Cognitive Assessment Tool for Schizophrenia (B-CATS) | 6, 9 and 12 month | 
| Changes from baseline in Neurocognition assessed by BACS | Brief Assessment of Cognition in Schizophrenia (BACS) | 6, 9 and 12 month | 
| Changes from baseline in Neurocognition assessed by UPSA-B | University of California San Diego Performance based Skills Assessment (UPSA-B) | 6, 9 and 12 month | 
| Changes from baseline in Neurocognition assessed by MASC | Movie for the Assessment of Social Cognition (MASC) | 6, 9 and 12 month | 
| Changes from baseline in Neurocognition assessed by PFA | Pictures of Facial Affect (PFA) | 6, 9 and 12 month | 
| Treatment adherence |  | 6, 9 and 12 month | 
| Changes in Cumulative dose of concomitant or rescue medication |  | 6, 9 and 12 month | 
| Changes of Biomarker: alterations of endocannabinoids and lipdomic profiling |  | 6, 9 and 12 month |