Clinical trial NCT02088060: A Four-week Clinical Trial Investigating Efficacy and Safety of Cannabidiol As a Treatment for Acutely Ill Schizophrenic Patients
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Schizophrenia
Lead sponsor: Central Institute of Mental Health, Mannheim
Sponsor class: OTHER
Collaborators: name: Martin-Luther-Universität Halle-Wittenberg
name: Heidelberg University
name: Technical University of Munich
name: Ludwig-Maximilians - University of Munich
name: Glostrup University Hospital, Copenhagen
First posted: 2014-03-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change in the Positive and Negative Syndrome Scale (PANSS) total score
timeFrame: within 4 weeks
Secondary outcomes:
measure: Changes in the PANSS subscores and clusters
timeFrame: within 4 weeks
measure: Changes in the Clinical Global Impression score
timeFrame: within 4 weeks
measure: Changes in the Global Assessment of Functioning Scale
timeFrame: within 4 weeks
measure: Changes in the Personal and Social Performance Scale
timeFrame: within 4 weeks
measure: Changes in the Calgary Depression Scale for Schizophrenia
timeFrame: within 4 weeks
measure: Changes in the Hamilton Anxiety Scale
timeFrame: within 4 weeks
measure: Changes in cognitive skills
timeFrame: within 4 weeks
measure: Response to antipsychotic medication
timeFrame: within 4 weeks
measure: Plasma levels of endogenous cannabinoids
timeFrame: within 4 weeks
measure: Changes in physiological parameter
timeFrame: within 4 weeks
measure: Changes in the UKU Side Effect Rating Scale
timeFrame: within 4 weeks
measure: Columbia Suicidality Severity Rating Scale
timeFrame: within 4 weeks
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Psychiatric Centre Glostrup
city: Heidelberg
country: Germany
facility: Department of General Psychiatry, Heidelberg University
state: BW
city: Mannheim
country: Germany
facility: Dep. of Psychiatry and Psychotherapy, Central Institute of Mental Health
state: BW
city: Munich
country: Germany
facility: Dept. of Psychiatry and Psychotherapy, Ludwig-Maximillians-University Munich
state: BY
city: Munich
country: Germany
facility: Dept. of Psychiatry and Psychotherapy, Technical University Munich
state: BY
city: Halle
country: Germany
facility: Dept. of Psychiatry and Psychotherapy, Martin-Luther-University, Halle/Wittenberg
state: ST
Study officials:
affiliation: Central Institute of Mental Health
name: F. Markus Leweke, MD
role: PRINCIPAL_INVESTIGATOR
References: