Clinical trial NCT05316883: Biomarkers in Clozapine-responding Schizophrenia
Official title: Biomarkers in Clozapine-responding Schizophrenia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Schizophrenia
Psychosis
Lead sponsor: Mental Health Services in the Capital Region, Denmark
Sponsor class: OTHER
First posted: 2022-04-07
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: To compare biomarkers between clozapine responders and non-responder before and after 12 weeks of treatment
Primary purpose: BASIC_SCIENCE

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

Eligibility criteria: 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

Primary outcomes:
measure: Qalb
timeFrame: Baseline
measure: Change in Qalb
timeFrame: Baseline and after 12 weeks
measure: Change in IL-6 and TGF-beta
timeFrame: Baseline and after 12 weeks
Secondary outcomes:
measure: Change in FA, MD, AD and RD
timeFrame: Baseline and after 12 weeks
measure: Change in cortical thickness as measured with FreeSurfer
timeFrame: Baseline and after 12 weeks
measure: Change in glutamate in ACC and thalamus measured with MTI
timeFrame: Baseline and after 12 weeks
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Mental Health Services Glostrup, Unit for Complicated Schizophrenia
Study officials:
affiliation: Mental health Service, Glostrup
name: Jimmi Nielsen, PhD
role: PRINCIPAL_INVESTIGATOR
References: