Psychosis, Schizophrenia
Conditions
Brief summary
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 immunological markers and autoantibodies in the blood and cerebrospinal fluid, permeability of the blood-brain barrier and magnetic resonance imaging of structural, neurochemical and functional brain changes.
Detailed description
Patients will be examined before and after 12 weeks of treatment with clozapine Examinations at baseline and follow up will be: * Clinical ratings * Blood inflammatory markers * Inflammatory markers in cerebro spinal fluid * MRI : examination of grey & white matter, glutamate and GABA in Anterior Cingulate cortex and glutamate in thalamus, * selected cognitive measures
Interventions
DRUGClozapine
clinical doses adjusted to sideeffects and clinical effect
Sponsors
Jimmi Nielsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
To compare biomarkers between clozapine responders and non-responder before and after 12 weeks of treatment
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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 18-65 years; * Legally competent; * Stabil 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 chlorpromazine 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).
Exclusion criteria
* Involuntarily psychiatric admittance during the study * Substance abuse that interfere with compliance * 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, noUncontrolled * Current uncontrolled epilepsy * Current circulatory collapse and / or CNS depression for any cause * Current severe kidney, heart or liver disease * Current paralytic ileus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in IL-6 and TGF-beta | Baseline and after 12 weeks | Change in interleukin 6 (IL-6) and transcription growth factor beta (TGF-beta) |
| Qalb | Baseline | Quotient albumin (Qabl) in cerebrospinal fluid (CSF) compared to plasma |
| Change in Qalb | Baseline and after 12 weeks | Change in quotient albumin in cerebrospinal fluid compared to plasma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in FA, MD, AD and RD | Baseline and after 12 weeks | Change in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) |
| Change in cortical thickness as measured with FreeSurfer | Baseline and after 12 weeks | Change in cortical thickness as measured with FreeSurfer |
| Change in glutamate in ACC and thalamus measured with MTI | Baseline and after 12 weeks | Change in glutamate in anterior cingulate cortex (ACC) and thalamus measured with magnetic transfer imaging (MTI) |
Countries
Denmark
Contacts
CONTACTJimmi Nielsen, PhD
CONTACTMette Nielsen, PhD
PRINCIPAL_INVESTIGATORJimmi Nielsen, PhD
Mental health Service, Glostrup
Outcome results
None listed