Clinical trial NCT02926859: Enhancing Recovery in Early Schizophrenia
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Schizophrenia
Lead sponsor: Central Institute of Mental Health, Mannheim
Sponsor class: OTHER
First posted: 2016-10-06
Enrollment: 180
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: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: All-cause discontinuation
timeFrame: within 12 month
Secondary outcomes:
measure: Improvement in Psychopathology assessed by PANSS
timeFrame: 6, 9 and 12 month
measure: Improvement in Psychopathology assessed by CGI
timeFrame: 6, 9 and 12 month
measure: Improvement in Psychopathology assessed by BSI-53
timeFrame: 6, 9 and 12 month
measure: Improvement in Psychopathology assessed by FROGS
timeFrame: 6, 9 and 12 month
measure: Changes from baseline in Depression Scale
timeFrame: 6, 9 and 12 month
measure: Improvement in social and occupational functioning assessed by GAF
timeFrame: 6, 9 and 12 month
measure: Improvement in social and occupational functioning assessed by PSP
timeFrame: 6, 9 and 12 month
measure: Improvement in social and occupational functioning assessed by EMA
timeFrame: 6, 9 and 12 month
measure: Improvement in Quality of life assessed by WHOQUOL-Bref
timeFrame: 6, 9 and 12 month
measure: Improvement in Quality of life assessed by LQLP
timeFrame: 6, 9 and 12 month
measure: Changes from baseline in Neurocognition assessed by B-CATS
timeFrame: 6, 9 and 12 month
measure: Changes from baseline in Neurocognition assessed by BACS
timeFrame: 6, 9 and 12 month
measure: Changes from baseline in Neurocognition assessed by UPSA-B
timeFrame: 6, 9 and 12 month
measure: Changes from baseline in Neurocognition assessed by MASC
timeFrame: 6, 9 and 12 month
measure: Changes from baseline in Neurocognition assessed by PFA
timeFrame: 6, 9 and 12 month
measure: Treatment adherence
timeFrame: 6, 9 and 12 month
measure: Changes in Cumulative dose of concomitant or rescue medication
timeFrame: 6, 9 and 12 month
measure: Changes of Biomarker: alterations of endocannabinoids and lipdomic profiling
timeFrame: 6, 9 and 12 month
Other outcomes:
measure: Side effects: weight gain
timeFrame: 6, 9 and 12 month
measure: Side effects: Vital Signs
timeFrame: 6, 9 and 12 month
measure: Side effects: UKU Side Effect rating scale
timeFrame: 6, 9 and 12 month
measure: Side effects: Abnormal Involuntary Movement Scale (AIMS)
timeFrame: 6, 9 and 12 month
measure: Side effects: Evaluation of extrapyramidal symptoms (EPS)
timeFrame: 6, 9 and 12 month
measure: Side effects: physical and neurological examination
timeFrame: 6, 9 and 12 month
measure: Standard blood tests
timeFrame: 6, 9 and 12 month
measure: Columbia Suicidality Sverity Rating Scale (C-SSRS)
timeFrame: 6, 9 and 12 month
Locations:
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: Berlin
country: Germany
facility: Dept. of Psychiatry and Psychotherapy, Charité, Campus Charité-Mitte
state: B
city: Aachen
country: Germany
facility: Department of Psychiatry, Psychotherapy, and Psychosomatics, RWTH Aachen
state: NRW
city: Cologne
country: Germany
facility: Dept. of Psychiatry and Psychotherapy, University Hospital of Cologne
state: NRW
city: Hamburg
country: Germany
facility: Department of Psychiatry und Psychotherapy, University Hospital Hamburg-Eppendorf
Study officials:
affiliation: Central Institute of Mental Health
name: F. Markus Leweke, MD
role: PRINCIPAL_INVESTIGATOR
References: