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Biomarkers in Clozapine-responding Schizophrenia (BiCS)

Primary Purpose

Schizophrenia, Psychosis

Status
Recruiting
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Clozapine
Sponsored by
Mental Health Services in the Capital Region, Denmark
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Schizophrenia

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mental Health Services Glostrup, Unit for Complicated SchizophreniaRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

clozapine treatment

Arm Description

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

Outcomes

Primary Outcome Measures

Qalb
Quotient albumin (Qabl) in cerebrospinal fluid (CSF) compared to plasma
Change in Qalb
Change in quotient albumin in cerebrospinal fluid compared to plasma
Change in IL-6 and TGF-beta
Change in interleukin 6 (IL-6) and transcription growth factor beta (TGF-beta)

Secondary Outcome Measures

Change in FA, MD, AD and RD
Change in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD)
Change in cortical thickness as measured with FreeSurfer
Change in cortical thickness as measured with FreeSurfer
Change in glutamate in ACC and thalamus measured with MTI
Change in glutamate in anterior cingulate cortex (ACC) and thalamus measured with magnetic transfer imaging (MTI)

Full Information

First Posted
September 30, 2020
Last Updated
April 6, 2022
Sponsor
Mental Health Services in the Capital Region, Denmark
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1. Study Identification

Unique Protocol Identification Number
NCT05316883
Brief Title
Biomarkers in Clozapine-responding Schizophrenia
Acronym
BiCS
Official Title
Biomarkers in Clozapine-responding Schizophrenia
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 28, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mental Health Services in the Capital Region, Denmark

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Psychosis

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
To compare biomarkers between clozapine responders and non-responder before and after 12 weeks of treatment
Masking
None (Open Label)
Allocation
N/A
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
clozapine treatment
Arm Type
Other
Arm Description
Open label clozapine will be given to all participants in clinical doses adjusted to sideeffects and clinical effect
Intervention Type
Drug
Intervention Name(s)
Clozapine
Intervention Description
clinical doses adjusted to sideeffects and clinical effect
Primary Outcome Measure Information:
Title
Qalb
Description
Quotient albumin (Qabl) in cerebrospinal fluid (CSF) compared to plasma
Time Frame
Baseline
Title
Change in Qalb
Description
Change in quotient albumin in cerebrospinal fluid compared to plasma
Time Frame
Baseline and after 12 weeks
Title
Change in IL-6 and TGF-beta
Description
Change in interleukin 6 (IL-6) and transcription growth factor beta (TGF-beta)
Time Frame
Baseline and after 12 weeks
Secondary Outcome Measure Information:
Title
Change in FA, MD, AD and RD
Description
Change in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD)
Time Frame
Baseline and after 12 weeks
Title
Change in cortical thickness as measured with FreeSurfer
Description
Change in cortical thickness as measured with FreeSurfer
Time Frame
Baseline and after 12 weeks
Title
Change in glutamate in ACC and thalamus measured with MTI
Description
Change in glutamate in anterior cingulate cortex (ACC) and thalamus measured with magnetic transfer imaging (MTI)
Time Frame
Baseline and after 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jimmi Nielsen, PhD
Phone
4538640885
Email
jimmi.nielsen@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Mette Nielsen, PhD
Email
mette.oedegaard.nielsen@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jimmi Nielsen, PhD
Organizational Affiliation
Mental health Service, Glostrup
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mental Health Services Glostrup, Unit for Complicated Schizophrenia
City
Glostrup
ZIP/Postal Code
2600
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mette Ødegaard Nielsen, MD, PhD
Phone
38640884
Email
mette.oedegaard.nielsen@regionh.dk
First Name & Middle Initial & Last Name & Degree
Bahast Biuk, MD
Phone
38640884
Email
bahast.biuk.01@regionh.dk

12. IPD Sharing Statement

Plan to Share IPD
No

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Biomarkers in Clozapine-responding Schizophrenia

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