Enhancing Recovery in Early Schizophrenia

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

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.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Cannabidiol as add-on; Drug: Placebo as add-on

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: F. Markus Leweke, MD; Phone Number: +49 621 1703 2321; Email: leweke@cimh.de
• Study Contact Backup: Name: Cathrin Rohleder, PhD; Phone Number: +49 621 1703 2333; Email: rohleder@cimh.de

Study Locations

• Germany
  • Hamburg, Germany, 20246
    • Recruiting
    • Department of Psychiatry und Psychotherapy, University Hospital Hamburg-Eppendorf
    • Contact: Daniel Schöttle, MD
    • Principal Investigator: Daniel Schöttle, MD
  • B
    • Berlin, B, Germany, 10117
      • Recruiting
      • Dept. of Psychiatry and Psychotherapy, Charité, Campus Charité-Mitte
      • Contact: Henrik Walter, MD, PhD; Email: henrik.walter@charite.de
      • Principal Investigator: Henrik Walter, MD, PhD
  • BW
    • Mannheim, BW, Germany, 68159
      • Recruiting
      • Dep. of Psychiatry and Psychotherapy, Central Institute of Mental Health
      • Contact: F. Markus Leweke, MD; Phone Number: 2761 +49 621 1703; Email: leweke@cimh.de
      • Principal Investigator: F. Markus Leweke, MD
  • BY
    • Munich, BY, Germany, 80336
      • Not yet recruiting
      • Dept. of Psychiatry and Psychotherapy, Ludwig-Maximillians-University Munich
      • Contact: Peter Falkai, MD; Email: Peter.Falkai@med.uni-muenchen.de
      • Principal Investigator: Peter Falkai, MD
  • NRW
    • Aachen, NRW, Germany, 52074
      • Recruiting
      • Department of Psychiatry, Psychotherapy, and Psychosomatics, RWTH Aachen
      • Contact: Tanja Veselinovic, MD; Email: tveselinovic@ukaachen.de
      • Principal Investigator: Tanja Veselinovic, MD
    • Cologne, NRW, Germany, 50924
      • Recruiting
      • Dept. of Psychiatry and Psychotherapy, University Hospital of Cologne
      • Contact: Joseph Kambeitz, MD; Email: Joseph.Kambeitz@uk-koeln.de
      • Principal Investigator: Joseph Kambeitz, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cannabidiol; Cannabidiol as add-on to individualized pharmacological treatment	Drug: Cannabidiol as add-on; 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
Placebo Comparator: Placebo; Placebo as add-on to individualized pharmacological treatment	Drug: Placebo as add-on; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects: weight gain	Body Mass Index, abdominal girth	6, 9 and 12 month
Side effects: Vital Signs	heart rate, blood pressure, electrocardiography	6, 9 and 12 month
Side effects: UKU Side Effect rating scale		6, 9 and 12 month
Side effects: Abnormal Involuntary Movement Scale (AIMS)		6, 9 and 12 month
Side effects: Evaluation of extrapyramidal symptoms (EPS)		6, 9 and 12 month
Side effects: physical and neurological examination		6, 9 and 12 month
Standard blood tests		6, 9 and 12 month
Columbia Suicidality Sverity Rating Scale (C-SSRS)		6, 9 and 12 month

Collaborators and Investigators

• Sponsor: Central Institute of Mental Health, Mannheim
• Investigators: Principal Investigator: F. Markus Leweke, MD, Central Institute of Mental Health

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2017
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 7, 2016
• First Submitted That Met QC Criteria: October 4, 2016
• First Posted (Estimated): October 6, 2016

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: CBD-ESPRIT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No