CLEAR (CLozapine in EARly Psychosis) is investigating the effectiveness of clozapine versus other antipsychotics (known here as treatment as usual or TAU) in young people under the age of 25.
Research on antipsychotics in young people and children shows that antipsychotics do help children and young people with psychosis. However, there is very limited research focussed on clozapine in young people, so it is not clear whether or not clozapine should be recommended for people under 25.
For these reasons, the National Institute of Health Research (NIHR) has commissioned this research to study clozapine as a treatment for psychosis in people under 25. The results will help the National Institute for Health and Care Excellence (NICE) decide which treatment they should recommend, so it should help other people to receive the best treatment in the future.
We plan to recruit 260 participants across England and Wales. Inclusion criteria includes young people with schizophrenia or a related disorder, aged between 12 to 24 years who meet NICE criteria for treatment resistance. A computer will randomly decide whether participants take clozapine or another antipsychotic (decided by the treating doctor) for 12 weeks. A researcher will meet the participant 4 times, firstly at a baseline visit prior to randomisation and treatment commencing and then a further 3 times to complete some questionnaires and clinical assessments.
After 12 weeks of treatment, participants can discuss with their clinical team whether they want to continue the treatment allocated in the trial or change it to something else. A further 2 follow ups will be organised between the researcher and the participant at 6 months and 12 months.
At some recruitment sites (please see ‘Recruitment sites’ for participating Trusts) an additional sub-study will also be offered. This add-on study investigates the biological changes that occur in the brain and blood when treated with clozapine or other antipsychotics and how they relate to symptom improvement. This biomarker study is also funded by the NIHR. Participation will involve having a magnetic resonance imaging (MRI) brain scan and providing a blood sample, once at baseline and again at the end of the 12 week treatment period. An MRI is used to take pictures of the brain and the participant lies down still in the machine, for up to 75 minutes, to enable this.
Participants will be compensated for their time and travel expenses.
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CLEAR aims to evaluate the clinical and cost effectiveness of clozapine compared to standard antipsychotic treatment in children and young adults (12-24 years) with treatment resistant psychosis.
Full eligibility criteria and current Protocol available here
Lead Investigator: Professor Alice Egerton
The MRI add-on study is investigating the biological mechanisms that underlie the efficacy of clozapine in treatment resistant schizophrenia (TRS).
The primary research aim is to develop understanding of the biological mechanisms that contribute to the superior efficacy of clozapine over standard antipsychotic treatment. We hope this will help to provide a rational basis for the development of new treatments. Based on the existing scientific literature and our previous research, we propose that reductions in inflammatory and glutamatergic features of TRS contribute to the efficacy of clozapine.
A secondary aim is to determine whether these biomarkers, measured before commencing clozapine treatment, can, together with clinical data, predict how well symptoms are likely to subsequently improve during clozapine treatment.
The target recruitment is 90 participants. Recruitment sites participating form part of the London, Oxford and Manchester hubs. MRI scans are taking place at Centre for Neuroimaging Sciences, King’s College London, Wellcome Centre for Integrative Neuroimaging (WIN), University of Oxford and NIHR/Wellcome Trust Manchester Clinical Research Facility, Manchester University NHS Foundation Trust (MFT).
The CLEAR study includes six participating academic centres, King’s College London, University College London, University of Oxford, University of Birmingham, University of Manchester and Cardiff University. These 6 hubs will act as a coordinating centre for their surrounding NHS Trusts and Health Boards acting as recruitment sites (approx. 25 across the UK, N.B. site list generated pre study start).
Co-applicants include Professor Paramala Santosh (South London and Maudsley NHS Foundation Trust), Professor Helen Killaspy (University College London), Professor Richard Emsley, Professor Sarah Byford, Professor Oliver Howes, Dr Cecilia Casetta (King’s College London), Dr Daniel Hayes (South London and Maudsley NHS Foundation Trust), Professor Richard Drake (The University of Manchester), Dr Rachel Elvins (Manchester University NHS Foundation Trust), Professor James Walters, Professor Jonathan Bisson (Cardiff University), Professor Belinda Lennox (University of Oxford), Dr Anthony James (Oxford Health NHS Foundation Trust), Professor Rachel Upthegrove (University of Birmingham), Dr Nicole Fung (Birmingham Women’s and Children’s NHS Foundation Trust), Dr Charles Dixon (Devon Partnership NHS Foundation Trust).