Treatment-resistant psychosis Mental and Behavioural Disorders
Conditions
Interventions
Current interventions as of 16/07/2025:
Multi-centre, open-label, blind-rated (primary outcome), 1:1 observational study of clozapine versus treatment as usual in children and young people (<25) with
(Maximum dose = 900 mg per day), at the discretion of the prescriber, for 12 weeks. Following this, if clozapine is continued, it will no longer be classified as an investigational medicinal product.
Sponsors
King's College London
South London and Maudsley NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 16/07/2025: 1. Age =12 and 4 5. Clinician Rating Scale [24] (CRS) =3 6. Capacity to give informed consent OR has a legal representative able to give consent to the trial _____ Previous inclusion criteria as of 24/04/2025: 1. Age =12 and 4 5. Clinician Rating Scale [24] (CRS) >3 6. English or Welsh language sufficient to participate 7. Capacity to give informed consent OR has a legal representative able to give consent to the trial _____ Previous inclusion criteria as of 13/03/2024: 1. Age =12 and 4 5. Clinician Rating Scale [24] (CRS) >3. 6. English or Welsh language sufficient to participate. 7. Capacity to give informed consent OR has a legal representative able to give consent to the trial. _____ Previous inclusion criteria: 1. Age =12 and 4 5. Compliance Rating Scale [23] (CRS) >3 6. English or Welsh language sufficient to participate 7. Capacity to give informed consent OR has
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 16/07/2025: 1. Psychosis predominantly caused by substance misuse. 2. Pregnancy. 3. Breastfeeding. 4 Women of child-bearing potential (WOCBP*) not using at least acceptable methods of contraception** during the trial 5. Previous adequate trial of clozapine. 6. CNS disorders (ICD-10 G00-26; G40-41, G45-46; G80-94, G97). 7. Concurrent medications with documented interactions with antipsychotics. 8. Participation in a clinical trial involving any unlicensed investigational medical product (within the last 3 months. 9. Positive test for COVID-19 within the past 10 days. 10. Current Electroconvulsive Therapy (ECT) * WOCBP defined as: fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. ** acceptable methods of contraception include: • progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action • male or female condom with or without spermicide *** • cap, diaphragm or sponge with spermicide *** *** A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) are also considered acceptable, but not highly effective, birth control methods Acceptable methods are the minimum requirement. It should be noted that the requirement for ‘at least acceptable methods of contraception’ would include the above methods but also include all ‘highly effective’ methods listed below: 1. Combined (estrogen and progestogen containing) hormonal 2. Contraception associated with inhibition of ovulation 1: 2.1. Oral 2.2. Intravaginal 2.3. Transdermal 3. Progestogen-only hormonal contraception associated with inhibition of ovulation 1: 3.1. Oral 3.2. Injectable 3.3. Implantable 4. Intrauterine device (IUD) 5. Intrauterine hormone-releasing system ( IUS) 6. Bilateral tubal occlusion 7. Vasectomised partner 8. Sexual abstinence (if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments) Previous exclusion criteria as of 13/03/2024: 1. Psychosis predominantly caused by substance misuse. 2. Pregnancy. 3. Breastfeeding. 4 Women of child-bearing potential (WOCBP*) not using at least acceptable methods of contraception** during the trial 5. Contraindications to clozapine as listed in SmPC as follows: 5.1. Hypersensitivity to the active substance or to any of the excipients, listed in section 6.1. 5.2. Patients unable to undergo regular blood tests. 5.3. History of toxic or idiosyncratic granulocytopenia/agranulocytosis (with the exception of granulocytopenia/agranulocytosis from previous chemotherapy). 5.4. History of clozapine-induced agranulocytosis. 5.5. Impaired bone marrow function. 5.6. Uncontrolled epilepsy. 5.7. Alcoholic and other toxic psychoses, drug intoxication, comatose conditions. 5.8. Circulatory collapse and/or CNS depression of any cause. 5.9. Severe renal or cardiac disorders (e.g. myocarditis). 5.10. Active liver disease associated with nausea, anorexia or jaundice; progressive liver disease, hepatic failure. 5.11. Paralytic ileus. 5.12. Clozapine treatment must not be started concurrently with substances known to have a substantial potential for causing agranulocytosis; concomitant use of depot antipsychotics is to be di
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in total PANSS score from baseline to 12 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures: Assessment will take place at weeks 6 and 12: 1. Change in overall clinical impression (CGI) 2. Clinician rated level of adherence (CRS) 3. Side effects (GASS-C) 4. Quality of life (EQ-5D-Y) 5. Subjective experience (DAI-10) 6. Psychotropic treatment, service use and readmission rate, (EI-AD-SUS) 7. Change in PANSS sub-scale (positive, negative and general), and weight gain Previous secondary outcome measures: Assessment will take place at weeks 6, 12, 24 and 52: 1. Change in overall clinical impression (CGI) 2. Clinician rated level of adherence (CRS) 3. Side effects (GASS-C) 4. Quality of life (EQ-5D-Y) 5. Subjective experience (DAI-10) 6. Psychotropic treatment, service use and readmission rate, (EI-AD-SUS) 7. Change in PANSS sub-scale (positive, negative and general), and weight gain Added 01/02/2023: In the embedded mechanistic study, outcomes will include, from baseline to 12 weeks: 1. Change in brain glutamate, measured using proton magnetic resonance spectroscopy (1H-MRS) 2. Change in brain glutathione, measured using 1H-MRS 3. Change in regional cerebral blood flow, measured using arterial spin labelling 4. Change in peripheral levels of glutathione and cytokines | — |
Countries
England, United Kingdom
Outcome results
None listed