Schizophrenia Mental and Behavioural Disorders Schizophrenia
Conditions
Interventions
Patients who have a diagnosis of psychotic disorder and having residual symptoms inspite of taking first-line antipsychotics will be recruited if they meet the conditions for participation.
Sponsors
King's College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 04/05/2021: 1. Aged 18 and above at the time of consent 2. Adequate command of English to understand the information leaflet 3. Capacity to consent to participation in the study 4. Confirmation of DSM-5 diagnosis of schizophrenia or schizoaffective disorder using SCID-5 5. PANSS total symptom severity score > 70 6. At least one PANSS psychotic item rating of at least moderate severity (> 3 on one or more psychotic item rating in PANSS) 7. Received treatment with at least one non-clozapine antipsychotic drug at adequate dose (as defined by Maudsley guidelines)for a duration of at least 6 weeks and in case of a depot be stable for at least 2 treatment cycles or at least 30 days 8. On a stable dose of antipsychotic treatment for at least 2 weeks in case of oral dosage forms 9. Good adherence to antipsychotic treatments as determined by a score > 4 on the Medication Adherence rating scale 10. Female subject of child bearing potential must agree to the MHRA pregnancy prevention programme which includes a negative serum pregnancy test, use of a highly effective form of birth control and signing an annual risk acknowledgement form _____ Previous inclusion criteria: 1. Aged 18 and above at the time of consent 2. Adequate command of English to understand the information leaflet 3. Capacity to consent to participation in the study 4. Confirmation of DSM-5 diagnosis of schizophrenia or schizoaffective disorder using SCID-5 5. PANSS total symptom severity score > 70 6. At least one PANSS psychotic item rating of at least moderate severity (> 3 on one or more psychotic item rating in PANSS) 7. Received treatment with at least one non-clozapine antipsychotic drug at adequate dose (as defined by Maudsley guidelines)for a duration of at least 6 weeks and in case of a depot be stable for at least 2 treatment cycles or at least 30 days 8. On a stable dose of antipsychotic treatment for at least 2 weeks in case of oral dosage forms 9. Good adherence to antipsychotic treatments as determined by a score > 4 (ideally > 6) on the Medication Adherence rating scale 10. Female subject of child bearing potential must agree to the MHRA pregnancy prevention programme which includes a negative serum pregnancy test, use of a highly effective form of birth control and signing an annual risk acknowledgement form
Exclusion criteria
Exclusion criteria: 1. Subject having a rating of 4 or above on the clinical frailty scale 2. Female subject who is pregnant or breast-feeding 3. Subject with a known history of urea cyclic disorder 4. Subject with a known history of porphyria 5. Subject with a known history of severe renal insufficiency 6. Subject with a known history of a mitochondrial disorder and in the opinion of the recruiting researcher will impair the safety of the subject and/or the scientific integrity of the study 7. Subject with carnitine palmitoyltransferase (CPT) type II deficiency 8. Subject currently taking clozapine 9. Subject currently taking valproate 10. Subject who had stopped taking valproate in the past six weeks prior to screening due to adverse effects 11. Any recent change (<2 weeks) change in antipsychotic regimen 12. Subject answers “yes” to “Suicide Ideation” Items 4 (active suicide ideation) with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) on the C-SSR during the screening visit 13. Subject has attempted suicide within 3 months prior to screening 14. Subject having known hypersensitivity to valproate or other ingredients in the tablet or placebo 15. Significant sustained abnormality when vital signs are measured at screening 16. Patients with a personal or family history of significant liver disease (e.g. severe hepatic dysfunction, cirrhosis) 17. Any other medical condition in the opinion of the recruiting researcher that will impair the safety of the subject and/or the scientific integrity of the study 18. Participation in a clinical trial within 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) 19. Participation in a research study that in the opinion of the investigator will affect the safety of the volunteer or scientific integrity of either study 20. Taking a drug that may have a clinically significant effect on the metabolism of valproate or where valproate may have a clinically significant effect on its metabolism including oxcarbazepine, lamotrigine, phenobarbital, primidone, phenytoin, ethosuximide, rufinamide, phenytoin, carbapenem antibiotics, topiramate, acetazolamide, warfarin and other coumarin anticoagulants and in the opinion of the recruiting researcher will impair the safety of the subject and/or the scientific integrity of the study (added 04/05/2021) 21. Women of childbearing potential unwilling to follow the study contraception requirements 22. Subject with a known history of active liver disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Psychotic (positive), negative and general symptom severity in schizophrenia measured using the Positive and Negative Syndrome Scale (PANSS) positive subscale at the 12-month visit | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Psychotic (positive) symptom severity in schizophrenia measured using the PANSS positive score at 6 months 2. Psychotic (positive), negative and general symptom severity in schizophrenia measured using the PANSS at 3, 6 and 12 months 3. Psychotic (positive), negative and general symptom severity (PANSS) factor scores at baseline at 3, 6 and 12 months 4. Severity of the patient’s illness measured using the Clinical Global Impression scale (Schizophrenia version) at baseline, 3, 6 & 12-month follow-up visits 5. Aggression levels will be measured using the Modified Overt Aggression Scale at baseline, 3, 6 & 12-month follow-up visits 6. Depression will be measured using the Calgary depression scale for schizophrenia (CDSS) at baseline, 3, 6 & 12-month follow-up visits 7. Manic symptoms will be assessed using Young’s Mania rating scale (YMRS) will be measured at baseline, 3, 6 & 12-month follow-up visits 8. Patient reported outcomes will be evaluated using the Short Warwick-Edinburgh Well-being scale (SWEMWBS). It will be measured at baseline, 3, 6-month and 1-year time points 9. Cost effectiveness will be assessed using measures collected at baseline, 3, 6 & 12-month follow-up visits: the Client Service Receipt Inventory (CSRI), PANSS and the 36-item short form health survey (SF-36) 10. The discontinuation of the intervention will be measured at the 3, 6-month and 1-year time points. We will also record the cause of discontinuation under the following categories: (i) lack of efficacy, (ii) adverse effects, (iii) switch to clozapine, (v) lost to follow-up, (vi) contraindicated with medication that has been added or (vii) personal reasons 11. We will evaluate on an annual basis the long-term symptomatic and functional outcomes beyond the 12-month period primarily using electronic notes to determine service use ( | — |
Countries
England, Scotland, United Kingdom
Outcome results
None listed