The purpose of this trial is:
* To investigate whether the response to clozapine treatment can be enhanced by adding cannabidiol (CBD), compared to placebo, in treatment resistant psychosis patients.
* To confirm the safety of CBD in people with psychosis.
The trial is a randomised, double-blind, placebo-controlled, multi-centre, international, clinical trial. Individuals with a diagnosis of treatment resistant psychosis in their illness who have had a suboptimal or no response to clozapine treatment will be recruited. These patients are randomised to treatment with oral CBD 500mg twice daily, or a matching placebo for 12 weeks, in addition to clozapine, which is standard care treatment for this population. By using a battery of clinical outcome assessments, the trial will assess several optional biomarkers to predict clinical outcomes and response to treatment with CBD. Biomarkers are being assessed as an exploratory outcome measure. Participants will be invited to provide additional blood samples, stool samples, and complete neuroimaging assessments.
Who can participate
Age range16 Years – 50 Years
SexALL
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Inclusion criteria
✓. 16 to 50 years of age (inclusive) who are willing and able to provide written informed consent/assent (country specific requirements apply).
✓. The patient has been treated with clozapine for at least 8 weeks with a clozapine plasma concentration of at least 0.35 mg/L at screening. If a patient has a lower plasma concentration at screening, the patient can enter the trial at a later date once their plasma concentration is above the threshold\*.
✓. Within 10 years of first antipsychotic treatment prescribed for psychosis.
✓. The patient meets DSM-5 criteria for schizophrenia, schizoaffective disorder or schizophreniform disorder, as confirmed through the SCID-5-RV. The patient does not meet modified Andreasen et al (2005) criteria for symptomatic remission cross-sectionally (time requirement does not apply), i.e., a severity rating score of no more than mild (score of \</=3) on 8 specified Positive and Negative Syndrome Scale (PANSS) positive and negative symptom items: P1 - Delusions, P2 - Conceptual Disorganization, P3 - Hallucinatory Behaviour, N1 - Blunted Affect, N4 - Passive/Apathetic Social Withdrawal, N6 - Lack of Spontaneity and Flow of Conversation, G5 - Mannerisms and Posturing, G9 - Unusual Thought Content.
✓. Patients of child-bearing potential\*\* must be willing to ensure that they use highly effective contraception during the trial and as per the requirements in the protocol\*\*\*.
✓. In the Investigator's opinion, is able and willing to comply with all trial requirements.
What they're measuring
1
Change in Positive and Negative Syndrome Scale (PANSS) total score
✓. Willing to allow their General Practitioner and/or consultant, if required by local guidelines/regulations, to be notified of participation in the trial.
✓. For patients who take part in the optional MRI scans: they must be eligible for MRI scanning as per local requirements, for example concerning e.g. implants, braces etc.
Exclusion criteria
✕. Current treatment with sodium valproate, valproate semisodium, or clobazam. In cases of current use of these medicines, participation is only permitted if they can and will be discontinued or switched to a suitable alternative medication prior to randomisation.
✕. Hypersensitivity to the active substance, sesame oil, sesame seed or any of the excipients of the trial intervention.
✕. Known hepatic insufficiency and/or transaminase elevations levels exceeding the upper limit of normal 2 times or more and bilirubin greater than 1.5 times the upper limit of normal.
✕. Previous neurosurgery or neurological disorder, including epilepsy, which may affect the trial procedures\*.
✕. IQ \<70 as measured by a validated IQ test e.g. Wechsler Abbreviated Scale of Intelligence (WASI), Wechsler Adult Intelligence Scale (WAIS), and Wechsler Intelligence Scale for Children (WISC), as approved for local languages and appropriate for the participant's age.
✕. Pregnancy or breastfeeding.
✕. The patient has a current diagnosis of 'Substance or medication induced psychotic disorder' or 'Psychotic disorder due to another medical condition' as determined through the SCID-5-RV.
✕. Current active suicidal ideation within the last 2 weeks, defined as a score of 1 or higher on CDSS question 8, followed by an assessment by the treating clinician who determines it is not safe for the patient to participate in the trial\*\*