SchizophreniaPhase 4BiCSNCT05316883
Biomarkers in Clozapine-responding Schizophrenia
A Phase 4 study testing Clozapine in people with Schizophrenia and Psychosis, run by Jimmi Nielsen at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Schizophrenia, Psychosis
- What is being tested?
- Clozapine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteDenmark
- Study dates
- 28 Feb 2021to 31 Dec 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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).
Who cannot join
- 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
Show all 10Show fewer
- Current uncontrolled epilepsy
- Current circulatory collapse and / or CNS depression for any cause
- Current severe kidney, heart or liver disease
- Current paralytic ileus
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Mette Nielsen, PhD contact
Denmark1 site, 1 recruiting
- Recruiting
Mental Health Services Glostrup, Unit for Complicated Schizophrenia
Glostrup Municipality, Denmark, 2600
Mette Ødegaard Nielsen, MD, PhD, 38640884, mette.oedegaard.nielsen@regionh.dk
Bahast Biuk, MD, 38640884, bahast.biuk.01@regionh.dk
About this study
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.
Read the 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
- Conditions
- Schizophrenia, Psychosis
- Being tested
- Clozapine
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClozapineDrug
clinical doses adjusted to sideeffects and clinical effect
| Study group | Role | What they receive |
|---|---|---|
| clozapine treatment | Other | Open label clozapine will be given to all participants in clinical doses adjusted to sideeffects and clinical effect Receives: Drug: Clozapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Qalb
Quotient albumin (Qabl) in cerebrospinal fluid (CSF) compared to plasma
Measured: Baseline
Change in Qalb
Change in quotient albumin in cerebrospinal fluid compared to plasma
Measured: Baseline and after 12 weeks
Change in IL-6 and TGF-beta
Change in interleukin 6 (IL-6) and transcription growth factor beta (TGF-beta)
Measured: Baseline and after 12 weeks
Secondary outcomes (3)
Change in FA, MD, AD and RD
Change in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD)
Measured: Baseline and after 12 weeks
Change in cortical thickness as measured with FreeSurfer
Change in cortical thickness as measured with FreeSurfer
Measured: Baseline and after 12 weeks
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)
Measured: Baseline and after 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2022
- Study start28 Feb 2021
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- To compare biomarkers between clozapine responders and non-responder before and after 12 weeks of treatment
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jimmi Nielsen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jimmi Nielsen, Copenhagen University Hospital, Hvidovre
- Investigators
- Jimmi Nielsen, PhD, Principal investigator, Mental health Service, Glostrup
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05316883
- Sponsor's protocol ID
- BiCS2019
- Acronym
- BiCS
- Status last verified
- Jan 2026
- First submitted
- 30 Sep 2020
- Last updated
- 20 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers in Clozapine-responding Schizophrenia
- ClinicalTrials.gov ID
- NCT05316883
- Acronym / sponsor ID
- BiCS / BiCS2019
- Conditions
- Schizophrenia, Psychosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Jimmi NielsenUniversity, hospital or other
- Study start
- 28 Feb 2021 (actual)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 7 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- To compare biomarkers between clozapine responders and non-responder before and after 12 weeks of treatment
| Arm | Type | Receives |
|---|---|---|
| clozapine treatment | Other | Drug: ClozapineOpen label clozapine will be given to all participants in clinical doses adjusted to sideeffects and clinical effect |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clozapineclinical doses adjusted to sideeffects and clinical effect | Drug | clozapine treatment |
Primary outcome
Qalb
Time frame: Baseline
Quotient albumin (Qabl) in cerebrospinal fluid (CSF) compared to plasma
Change in Qalb
Time frame: Baseline and after 12 weeks
Change in quotient albumin in cerebrospinal fluid compared to plasma
Change in IL-6 and TGF-beta
Time frame: Baseline and after 12 weeks
Change in interleukin 6 (IL-6) and transcription growth factor beta (TGF-beta)
3 secondary outcomes
Change in FA, MD, AD and RD
Time frame: Baseline and after 12 weeks
Change in cortical thickness as measured with FreeSurfer
Time frame: Baseline and after 12 weeks
Change in glutamate in ACC and thalamus measured with MTI
Time frame: Baseline and after 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mette Nielsen, PhD contact
Jimmi Nielsen, PhD principal investigator
Mental health Service, Glostrup
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clozapine in people with Schizophrenia and Psychosis, run by Jimmi Nielsen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jimmi Nielsen, PhD (4538640885, jimmi.nielsen@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Qalb (time frame: Baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2026.