A Four-week Clinical Trial Investigating Efficacy and Safety of Cannabidiol as a Treatment for Acutely Ill Schizophrenic Patients

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

Schizophrenia is a heterogeneous mental disorder that affects one percent of the world's population. Current antipsychotics 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. While cannabidiol has no psychotomimetic or addictive properties, it indirectly affects endogenous cannabinoid signalling by impairing the degradation of the endocannabinoid anandamide. In a controlled clinical trial of cannabidiol versus amisulpride (an established antipsychotic) in acute paranoid schizophrenics the investigators showed a significant clinical improvement in all symptoms of schizophrenia compared to baseline with either treatment. But cannabidiol displayed a significantly superior side-effect profile. This study is to evaluate the efficacy and safety of this novel treatment option in comparison to placebo and olanzapine, an established second generation antipsychotic in the treatment of acute schizophrenia and schizophrenia maintenance therapy, in a four-week clinical trial.

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Drug: Cannabidiol; Drug: Olanzapine; Drug: Placebo Cannabidiol; Drug: Placebo Olanzapine	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	150 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Four-week, Multicentre, Double-blinded, Randomised, Active- and Placebo- Controlled, Parallel-group Trial Investigating Efficacy and Safety of Cannabidiol in Acute, Early-stage Schizophrenic Patients
Study Start Date :	March 2014
Estimated Primary Completion Date :	August 2021
Estimated Study Completion Date :	December 2021

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Cannabidiol; Cannabidiol capsules 2x200 mg twice a day and placebo olanzapine capsule once a day over 4 weeks	Drug: Cannabidiol; Cannabidiol capsules Drug: Placebo Olanzapine; Placebo olanzapine capsules
Active Comparator: Olanzapine; Olanzapine capsule 15mg once a day and placebo cannabidiol capsules twice a day over 4 weeks	Drug: Olanzapine; Olanzapine capsules; Other Name: Olanzapine 1A pharma Drug: Placebo Cannabidiol; Placebo cannabidiol capsules
Placebo Comparator: Placebo; Placebo cannabidiol capsules twice a day and placebo olanzapine capsule once a day over 4 weeks	Drug: Placebo Cannabidiol; Placebo cannabidiol capsules Drug: Placebo Olanzapine; Placebo olanzapine capsules

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Change in the Positive and Negative Syndrome Scale (PANSS) total score [ Time Frame: within 4 weeks ]

Secondary Outcome Measures :

1. Changes in the PANSS subscores and clusters [ Time Frame: within 4 weeks ]
2. Changes in the Clinical Global Impression score [ Time Frame: within 4 weeks ]
3. Changes in the Global Assessment of Functioning Scale [ Time Frame: within 4 weeks ]
4. Changes in the Personal and Social Performance Scale [ Time Frame: within 4 weeks ]
5. Changes in the Calgary Depression Scale for Schizophrenia [ Time Frame: within 4 weeks ]
6. Changes in the Hamilton Anxiety Scale [ Time Frame: within 4 weeks ]
7. Changes in cognitive skills [ Time Frame: within 4 weeks ]
8. Response to antipsychotic medication [ Time Frame: within 4 weeks ]
9. Plasma levels of endogenous cannabinoids [ Time Frame: within 4 weeks ]
10. Changes in physiological parameter [ Time Frame: within 4 weeks ]
11. Changes in the UKU Side Effect Rating Scale [ Time Frame: within 4 weeks ]
12. Columbia Suicidality Severity Rating Scale [ Time Frame: within 4 weeks ]

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Informed consent given by the subject
• DSM-IV-TR diagnosis of schizophrenic psychosis (295.10, 295.20, 295.30, 295.90 (American Psychiatric Association)
• Patients must be within the first three years of illness, i.e. first diagnosis of schizophrenia is no older than three years.
• Age 18 to 65 years, male or female
• Minimal initial PANSS score of 75 at baseline
• Female patients of childbearing potential need to utilize a proper method of contraception.
• Body Mass Index between 18 and 40

Exclusion Criteria:

• Lack of accountability (assessed by an independent psychiatrist)
• History of treatment-resistant schizophrenia, defined as no response to at least two antipsychotics given for a minimum of 6 weeks each in an adequate dosage
• Positive urine drug-screening for illicit drugs at screening (except cannabinoids and benzodiazepines)
• Serious suicidal risk at screening visit (Subject to investigator's and independent psychiatrist's judgement: Poses a serious suicidal or homicidal risk at screening visit or has made a serious suicide attempt within the last 12 months prior to screening visit, or has exhibited homicidal behaviour at anytime during her/his lifetime)
• Known intolerance or allergy to olanzapine or cannabidiol
• Other relevant interferences of axis 1 (e.g. serious depression) according to diagnostic evaluation (MINI) including residual forms of schizophrenia
• Pregnancy, as determined through a β-HCG pregnancy test, or lactation

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Denmark
Psychiatric Centre Glostrup
Glostrup, Denmark, 2600
Germany
Department of General Psychiatry, Heidelberg University
Heidelberg, BW, Germany, 68115
Dep. of Psychiatry and Psychotherapy, Central Institute of Mental Health
Mannheim, BW, Germany, 68159
Dept. of Psychiatry and Psychotherapy, Ludwig-Maximillians-University Munich
Munich, BY, Germany, 80336
Dept. of Psychiatry and Psychotherapy, Technical University Munich
Munich, BY, Germany, 81675
Dept. of Psychiatry and Psychotherapy, Martin-Luther-University, Halle/Wittenberg
Halle, Saint, Germany, 06112

Sponsors and Collaborators

Central Institute of Mental Health, Mannheim

Martin-Luther-Universität Halle-Wittenberg

Heidelberg University

Technische Universität München

Ludwig-Maximilians - University of Munich

Glostrup University Hospital, Copenhagen

Investigators

Principal Investigator:	F. Markus Leweke, MD	Central Institute of Mental Health

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Central Institute of Mental Health, Mannheim
ClinicalTrials.gov Identifier:	NCT02088060 History of Changes
Other Study ID Numbers:	CBD-FEP; 2012-004335-23 ( EudraCT Number )
First Posted:	March 14, 2014
Last Update Posted:	March 8, 2018
Last Verified:	March 2018

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Olanzapine; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipsychotic Agents	Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents