E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Conditions with cronic psychotic symptoms |
Lidelser med kroniske psykotiske symptomer |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009134 |
E.1.2 | Term | Chronic schizophrenia |
E.1.2 | System Organ Class | 100000004873 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The outline of the current project is to establish a cohort of patients with treatment refractory schizophrenia eligible for clozapine, to identify clinical and biological characteristics of clozapine responding patients. Patients will be offered treatment with clozapine according to national clinical guidelines. Before clozapine is initiated, patients will be offered a thoroughly neurobiological examination, and re-examination will be carried out after 12 weeks of treatment. The primary focus of the examinations will be the permeability of the blood-brain barrier. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is immunological markers and autoantibodies in the blood and magnetic resonance imaging of structural, neurochemical and functional brain changes. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•According to ICD-10 fulfill diagnostic criteria for schizophrenia (F20.x), chronical paranoid psychoses (F22), Schizoaffective psychoses (F25) or other non-organic psychoses (F28/F29); •Age 18-64 years; •Legally competent; •Stable antipsychotic treatment during last month •Being treatment refractory according to TRIPP-guidelines (Howes et al. 2017) defined as having tried at least two antipsychotic drugs in sufficient dosage (≥600 mg clorpromazine equivalent) for a sufficient time (≥ 6 weeks) without sufficient symptom improvement (still a moderate level of positive symptoms). •Recreational use of substances is allowed as long as it does not interfere with compliance •Fertile females must use safe contraception (spiral or any hormonal contraception).
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E.4 | Principal exclusion criteria |
•Involuntarily psychiatric admittance during the study •Substance abuse that interfere with compliance •Any condition that interfere with compliance for obtaining bloodsamples weekly •Pregnancy (will be verified by urine-HCG-test in fertile females) •Toxic or idiosyncratic agranulocytosis in the past •Reduced bone marrow function according to blood samples •According to information from patient and available files, no -current uncontrolled epilepsy -current circulatory collapse and/or CNS depression for any cause -current severe kidney, heart or liver disease -current paralytic ileus
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E.5 End points |
E.5.1 | Primary end point(s) |
Permeability of the blood-brain-barrier blood and csf inflamatory cytokines
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline and after 12 weeks of clozapine treatment |
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E.5.2 | Secondary end point(s) |
Changes in brain white matter Changes in cortical thickness glutamate in ACC and thalamus |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
baseline and after 12 weeks of clozapine treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
biomarkers indicative of clozapine response |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |