Stratification and Treatment in Early Psychosis Study - ENHANCE
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age16-40
SponsorUniversity of Oxford
About this trial
The purpose of this study is:
* To investigate whether the response to antipsychotic treatment can be enhanced by adding cannabidiol (CBD) to the existing treatment, compared to placebo, in participants with a first episode of psychosis, who have had a suboptimal or no response to their first antipsychotic treatment. * To confirm the safety of CBD in people with psychosis.
The study is a randomized, double-blind, placebo-controlled, multi-centre, clinical trial. Individuals with a diagnosis of first-episode psychosis, who have had a suboptimal or no response to their first antipsychotic treatment will be recruited. These participants are randomised to treatment with CBD oral solution 500mg twice daily, or a matching placebo for 6 weeks, as an adjunct to their existing antipsychotic treatment. By using a battery of clinical outcome assessments, the trial will also assess several biomarkers to determine if they can be used 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 blood and stool samples, and may be asked to complete neuroimaging assessments at certain eligible sites.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
The participant is 16 to 40 years of age, willing and able to provide written informed consent/assent.
The participant is currently being treated with an antipsychotic for at least 3 weeks but no longer than 16 weeks.
The participant should be receiving at least the minimum dose of this antipsychotic for FEP according to modified Maudsley guidelines, as listed in Appendix B. The clinician should judge the participant to be a non-responder to this treatment and that increasing the dose further is unacceptable to the clinician and/or participant.
The compliance score associated with this antipsychotic medication is 4 or more on the Clinician Rating Scale (CRS).
Disqualifiers
Having been previously treated with a different antipsychotic (to the current one) at an adequate dose* for 4 weeks or longer.
Current or previous treatment with clozapine and/or 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 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.
Trial design
Design model
Parallel
Treatments tested in this trial
CBD 100 mg/mL Oral Solution
DrugDaily dose 1000mg, taken as 500mg (5ml) b.i.d for 6 weeks. For participants with a weight lower than 50 kg, the dose is to be adjusted to 20 mg/kg/day divided over 2 intakes of 10 mg/kg/day, for a period of 6 weeks
Placebo
Other intervention5ml b.i.d for 6 weeks; For participants with a weight lower than 50 kg, the dose is to be adjusted to 20 mg/kg/day divided over 2 intakes of 10 mg/kg/day, for a period of 6 weeks
Treatment groups
250 Participants
are divided into 2 treatment groupsGroup A: Cannabidiol (CBD)Experimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change in Positive and Negative Syndrome Scale (PANSS) total score
Change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to 6 weeks. The minimum value is 1 and the maximum value is 7 for each item of the scale. 1. A patient meets remission criteria if none of the following items score a 4 or higher: P1, P2, P3, N1, N4, N6, G5 and G9. 2. A patient does not meet remission criteria if one or more of these items score a 4 or higher.
Time frame
6 weeksSecondary outcomes
1
Change in symptoms (sub-scale scores)
Change in scores on the PANSS positive, negative and general symptom subscales from baseline to 6 weeks and 58 weeks (if participants consent to the optional 12 months long-term follow-up period).
Time frame
from baseline to 6 weeks and 58weeks2
Symptomatic remission
Symptomatic remission after 6 weeks and 58 weeks (if participants consent to the optional 12 months long-term follow-up period as measured using the PANSS, defined using Andreasen (2005) remission criteria. Andreasen, N. C., Carpenter, W. T., Jr, Kane, J. M., Lasser, R. A., Marder, S. R., \& Weinberger, D. R. (2005). Remission in schizophrenia: proposed criteria and rationale for consensus. The American journal of psychiatry, 162(3), 441-449. https://doi.org/10.1176/appi.ajp.162.3.441
Time frame
6 weeks and 58weeks3
Change in overall clinical impression
Change in overall clinical impression, assessed through Clinical Global Impression of Improvement and Severity (CGI-I/S) scales from baseline to 6 weeks and 58 weeks (if participant consent to the optional 12 months long-term follow-up period).
Time frame
from baseline to 6 weeks and 58weeks4
Change in functioning
Change in functioning, assessed through Social and Occupational Function Scale (SOFAS) from baseline to 6 weeks and 58 weeks (if participants consent to the optional 12 months long-term follow-up period). Score range 1-100, the higher score means the better function
Time frame
from baseline to 6 weeks and 58weeksOther outcomes
1
Change in overall patient impression of severity and improvement
Change in overall patient impression, assessed through Patient Global Impression of Improvement and Severity (PGI-I/S) scales from baseline to 6 weeks and 58 weeks (if participant consents to the optional 12 months long-term follow-up period) The Patient Global Impression of Improvement (PGI-I) is a single question asking the patient to rate how their psychotic symptoms is now compared to the previous study visit on a scale of 1. very much better to 7. very much worse. The lower score is better in symptoms' improvement. The Patient Global Impression of Severity (PGI-S) is a single question asking the patient to rate how their psychotic symptoms is now on a scale of 1. not present to 7. very severe. The lower score is better in symptoms.
Time frame
from baseline to 6 weeks and 58weeksSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Oxford
Lead sponsor
Wellcome Trust
Collaborator
Cambridge Cognition Ltd
Collaborator
Cambridgeshire and Peterborough NHS Foundation Trust
Collaborator
Oxford Health NHS Foundation Trust
Collaborator
West London NHS Trust
Collaborator
Charite University, Berlin, Germany
Collaborator
University of Cologne
Collaborator
Ludwig-Maximilians - University of Munich
Collaborator
The Sheba Fund for Health Services and Research
Collaborator
Shalvata Mental Health Center
Collaborator
Geha Mental Health Center
Collaborator
Amsterdam University Medical Center
Collaborator
Hospital General Universitario Gregorio Marañon
Collaborator
National and Kapodistrian University of Athens
Collaborator
Medical University of Vienna
Collaborator
Hospitales Universitarios Virgen del Rocío
Collaborator
University of Campania Luigi Vanvitelli
Collaborator
Psychiatric University Hospital, Zurich
Collaborator
Source ClinicalTrials.gov