Clinical Trial Results:
Cannabidiol as an add-on therapy in treatment-refractory psychotic disorders
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Summary
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EudraCT number |
2013-000240-26 |
Trial protocol |
GB |
Global end of trial date |
07 Aug 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Sep 2018
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First version publication date |
30 Sep 2018
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Other versions |
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Summary report(s) |
FINAL STUDY REPORT |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CBD_ADD_IN
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
King's College London
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Sponsor organisation address |
The Strand, London, United Kingdom, WC2R 2LS
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Public contact |
Paul Morrison, King's College London, 44 02078480057, paul.morrison@kcl.ac.uk
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Scientific contact |
Paul Morrison, King's College London, 44 02078480057, paul.morrison@kcl.ac.uk
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Sponsor organisation name |
South London & Maudsley NHS Foundation Trust
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Sponsor organisation address |
Bethlem Royal Hospital, Monks Orchard Road, Beckenham, United Kingdom, BR3 3BX
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Public contact |
Paul Morrison, South London & Maudsley NHS Foundation Trust, 44 02078480057, paul.morrison@kcl.ac.uk
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Scientific contact |
Paul Morrison, South London & Maudsley NHS Foundation Trust, 44 02078480057, paul.morrison@kcl.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
07 Aug 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 Jul 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Aug 2015
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To determine whether the addition of the molecule Cannabidiol (CBD) leads to improvement in the severity of core psychotic symptom, in patients experiencing their first psychotic episode who have failed to recover despite treatment with at least one standard anti-psychotic drug.
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Protection of trial subjects |
Subjects would continue to be seen by Community Mental Health team.
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Background therapy |
Participants will already be prescribed an oral antipsychotic medication (a dopamine-based pharmaceutical) at the time of entry into the study. In the majority of cases, this will be a 2nd generation drug (e.g. amisulpride, risperidone, olanzapine, quetiapine) in line with treatment guidelines in schizophrenia and local prescribing practice. CBD will be added to the existing dopamine-based treatment regime | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
25 Sep 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 5
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Worldwide total number of subjects |
5
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EEA total number of subjects |
5
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
5
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants recruited from the South London & Maudsley NHS Foundation Trust in the UK between July 2014 and August 2015. | ||||||||||
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Pre-assignment
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Screening details |
Screening visit to include Psychopathology assessments, metabolic assessments, MRI imaging, vital signs including body weight and urine drug screen. | ||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Full study | ||||||||||
Arm description |
An open-label, exploratory therapeutic trial of the molecule Cannabidiol in treatment refractory 1st episode psychosis (n=20), focusing on core psychological and metabolic outcomes. Cannabidiol will be added to an existing treatment regime (based on dopamine receptor antagonists) for 6-weeks duration. Clinical data will be collected over the duration of the trial, at 0, 2, 4 and 6 week time points. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Cannabidiol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Flexible titrated oral dosing as 100mg capsules x n/day (where n =1-8), Range: 200-800mg/day total, in 1-2 divided doses.
Initial starting dose = 4 capsules/day.
Flexible Dosing: If participants experience the 400mg/d dose as being too sedating, the dose will be reduced to 200mg/d. Blood pressure will be monitored before and after the first dosing of the IMP. If after two weeks, the participant tolerates the 400mg/d dose, the dose will be increased to 600mg/d. If after a further two weeks, the participant tolerates the 600mg/d dose, the dose will be increased to 800mg/d.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
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End points reporting groups
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Reporting group title |
Full study
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Reporting group description |
An open-label, exploratory therapeutic trial of the molecule Cannabidiol in treatment refractory 1st episode psychosis (n=20), focusing on core psychological and metabolic outcomes. Cannabidiol will be added to an existing treatment regime (based on dopamine receptor antagonists) for 6-weeks duration. Clinical data will be collected over the duration of the trial, at 0, 2, 4 and 6 week time points. | ||
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End point title |
Primary Endpoint [1] | ||||||||
End point description |
Scores on core psychotic symptoms and functioning, as
measured by the following scales:
- The Positive & Negative Syndrome Scale, PANSS22 (videotaped interview).
- The Global Assessment of Functioning Scale, GAF
- The Community Assessment of Psychotic Experiences,
CAPE-4222
- The Montgomery-Asberg Depression Rating Scale, MAD RS
- The Clinical Global Impression scale, CGI.
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End point type |
Primary
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End point timeframe |
Until end of trial participation for each participant
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Insufficient data for analysis |
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| Notes [2] - Insufficient data was obtained for analysis & trial prematurely terminated. PK sampling not done |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Continuous
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Whole Trial
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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07 Mar 2014 |
1) An additional secondary objective: “To determine whether measures of brain activity using magnetic resonance imaging can predict response to CBD, and whether these measures change with response to CBD”
2) The addition of the following endpoints: “Brain glutamate measures with 1H-MRS, blood flow using ASL and BOLD response with fMRI imaging methods”
3) A modification to the following inclusion criteria: Aged 18-6035 (inclusive) meeting DSM IV criteria for schizophrenia within the first 3 years of presentation to psychiatric services.
4) An update to the Investigator Brochure (Edition 6 August 2013) in the form of a Development Core Safety Information (DSCI) detailing a revision to section 7.6 (Safety), which will be included as appendix 3 to the current IB.
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27 Mar 2015 |
The amendment consists of the removal of one of the exclusion criteria. It is expected this will result in an increase in patient recruitment, and an, albeit slight, change in patient population studied, and is therefore deemed as a substantial amendment for the MHRA.
The following criteria was removed; Concomitant anti-depressant/anti-convulsant treatment for 2-months prior to study entry.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| July 2015 the IMP expired. The IMP was sent for analysis and was found to be unstable so a shelf-life so a shelf-life extension was not granted. Additionally the Science had moved on by this stage. Insufficient data had been obtained for analysis. | |||
