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BiCS: Biomarkers in Clozapine-responding Schizophrenia

Sponsor
Mental Health Services in the Capital Region, Denmark (Other)
Overall Status
Recruiting
CT.gov ID
NCT05316883
Collaborator
(none)
200
Enrollment
1
Location
1
Arm
46.1
Anticipated Duration (Months)
4.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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

Study Design

Study Type:
Interventional
Anticipated Enrollment :
200 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
To compare biomarkers between clozapine responders and non-responder before and after 12 weeks of treatmentTo compare biomarkers between clozapine responders and non-responder before and after 12 weeks of treatment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Biomarkers in Clozapine-responding Schizophrenia
Actual Study Start Date :
Feb 28, 2021
Anticipated Primary Completion Date :
Dec 31, 2024
Anticipated Study Completion Date :
Dec 31, 2024

Arms and Interventions

Arm Intervention/Treatment
Other: clozapine treatment

Open label clozapine will be given to all participants in clinical doses adjusted to sideeffects and clinical effect

Drug: Clozapine
clinical doses adjusted to sideeffects and clinical effect

Outcome Measures

Primary Outcome Measures

  1. Qalb [Baseline]

    Quotient albumin (Qabl) in cerebrospinal fluid (CSF) compared to plasma

  2. Change in Qalb [Baseline and after 12 weeks]

    Change in quotient albumin in cerebrospinal fluid compared to plasma

  3. 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)

Secondary Outcome Measures

  1. 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)

  2. Change in cortical thickness as measured with FreeSurfer [Baseline and after 12 weeks]

    Change in cortical thickness as measured with FreeSurfer

  3. 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)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 64 Years
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Mental Health Services Glostrup, Unit for Complicated Schizophrenia Glostrup Denmark 2600

Sponsors and Collaborators

  • Mental Health Services in the Capital Region, Denmark

Investigators

  • Principal Investigator: Jimmi Nielsen, PhD, Mental health Service, Glostrup

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Mental Health Services in the Capital Region, Denmark
ClinicalTrials.gov Identifier:
NCT05316883
Other Study ID Numbers:
  • BiCS2019
First Posted:
Apr 7, 2022
Last Update Posted:
Apr 7, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:
Schizophrenia
Clozapine

Study Results

No Results Posted as of Apr 7, 2022