Enhancing recovery in early schizophrenia: A study comparing cannabidiol and placebo as add-on to standard antipsychotic treatment.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Zentralinstitut Fuer Seelische Gesundheit

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

17 Feb 2017 → ongoing

Decision date (initial)

2024-11-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Endosane Pharmaceuticals GmbH · German Federal Ministry of Education and Research (BMBF)

External identifiers

EU CT number

2024-517198-26-00

EudraCT number

2014-003215-11

ClinicalTrials.gov

NCT02926859

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of cannabidiol compared to placebo as
an add-on to state-of-the-art antipsychotic maintenance
treatment of schizophrenia.

Secondary objectives 7

1. To evaluate improvements in psychopathology, social and occupational functioning.
2. To analyze changes in neurocognition.
3. To analyze safety and drug-drug interaction of cannabidiol in a long-term treatment.
4. To compare changes in cumulative dose of concomitant and rescue medication.
5. To evaluate alterations in endocannabinoid levels and lipidomic profiles.
6. To evaluate whether aberrations in oral microbial community structure and function accompany schizophrenia.
7. To quantify the incidence of extrapyramidal side-effects and weight gain.

Conditions and MedDRA coding

Remitted early phase schizophrenia

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Informed consent given by the subject
2. DSM-IV-TR diagnosis of schizophrenic psychosis (295.10, 295.20, 295.30, 295.90)
3. DSM-IV-TR diagnosis of schizophrenic psychosis (295.10, 295.20, 295.30, 295.90)
4. Patients must receive a stable oral dose of amisulpride (up to 1200 mg/day), aripiprazole (up to 30 mg/day), olanzapine (up to 20 mg/day), paliperidone (up to 12 mg/day), quetiapine (up to 750 mg/day), or risperidone (up to 10 mg/day) (TAU: treatment as usual) at least two weeks prior to inclusion in the study to ensure that the maximal effect of the previous medication has been received
5. Age 18 to 65 years, male or female
6. Initial PANSS total score of ≤ 75 at baseline
7. Female patients of childbearing potential need to utilize a proper method of contraception
8. Body Mass Index between 18 and 40 (Subjects with a BMI>40 and no further medical conditions that could indicate a metabolic syn-drome may enter the study based on the approval of the coordinating investigator)
9. Fluent in German or English

Exclusion criteria 8

1. Lack of accountability (assessed by an independent psychiatrist)
2. Treatment-resistant schizophrenia (TRS) defined as the persistence of symptoms despite ≥2 trials of antipsychotic medications of adequate dose and duration with documented adherence
3. Use of long-acting antipsychotics <3 months of end of proposed duration of action of respective dosage form prior to randomization
4. Positive urine drug-screening for illicit drugs at screening (except cannabinoids and benzodiazepines)
5. Serious suicidal risk at screening visit (Subject to investigator’s judgment)
6. Other relevant interferences of axis 1 (e.g., serious depression) according to diagnostic evaluation (M.I.N.I) including residual forms of schizophrenia
7. Other relevant neurological or other medical disorders
8. Pregnancy, determined through a β-HCG pregnancy test, or nursing (i.e., lactation at screening visit)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. All-cause discontinuation within 12 months following randomization as defined by any of the following conditions: 1) relevant worsening of symptoms; 2) not taking medication as prescribed for more than 14 consecutive days; 3) not keeping appointments as scheduled for more than six weeks; 4) not being traceable despite extensive efforts; withdrawal of informed consent; 6) termination of treatment on investigators request due to clinical reasons

Secondary endpoints 9

1. Improvement in Psychopathology from baseline (PANSS, CGI, BSI-53, FROGS), social and occupational functioning (GAF, PSP) and quality of life (WHOQUOL-Bref, LQLP).
2. Changes from baseline in the Calgary Depression Scale for Schizo-phrenia (CDSS).
3. Changes from baseline in Neurocognition.
4. Drug Attitude Inventory (DAI) and self-reported treatment adherence.
5. Changes of cumulative dose of concomitant or rescue medication.
6. Changes of biomarkers: alteration in endogenous cannabinoids and lipidomic profiling.
7. Changes from baseline in the UKU Side Effect Rating Scale, Abnormal Involuntary Movement Scale (AIMS) and evaluation of ex-trapyramidal symptoms (EPS).
8. Columbia Suicidality Severity Rating Scale (C-SSRS).
9. Other safety and tolerability assessments including (S)AEs, physical examination, abdominal girth, body mass index (BMI), vital signs (including heart rate and systolic and diastolic blood pressure in both supine and standing positions), ECG, assessments for neurological functioning and detailed laboratory assessments.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Zentralinstitut Fuer Seelische Gesundheit

Sponsor organisation

Zentralinstitut Fuer Seelische Gesundheit

Address

Luisenring J 5

City

Mannheim

Postcode

68159

Country

Germany

Scientific contact point

Organisation

Zentralinstitut Fuer Seelische Gesundheit

Contact name

F. Markus Leweke

Public contact point

Organisation

Zentralinstitut Fuer Seelische Gesundheit

Contact name

F. Markus Leweke

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications