Biomarkers linked to clozapine response in schizophrenia

Biomarkers in Clozapine-responding Schizophrenia

This project will test whether blood, spinal fluid, and brain scans can help predict which patients with treatment‑resistant schizophrenia will respond to clozapine.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years to 64 Years
• Sex: All
• Sponsor: Copenhagen University Hospital, Hvidovre (Academic / other)
• Locations: 1 site (Glostrup Municipality, Denmark)
• Trial ID: NCT05316883 on ClinicalTrials.gov

What this trial studies

The study will recruit patients with treatment‑refractory schizophrenia who are eligible for clozapine and perform detailed neurobiological testing before treatment and after 12 weeks on clozapine. Baseline and follow‑up examinations include clinical ratings, blood inflammatory markers and autoantibodies, cerebrospinal fluid inflammatory markers, MRI of brain structure and spectroscopy (glutamate and GABA), blood–brain barrier permeability measures, and selected cognitive tests. Participants will receive clozapine according to national clinical guidelines and clinical response will be related to the biological measures. The goal is to identify clinical and biological characteristics that distinguish clozapine responders from non‑responders.

Who should consider this trial

Good fit: Ideal candidates are adults 18–65 with treatment‑refractory non‑organic psychosis or schizophrenia per ICD‑10 and TRIPP criteria, legally competent, on stable antipsychotic treatment in the prior month, and willing to undergo MRI, blood draws and lumbar puncture and to start clozapine.

Not a fit: Patients who are involuntarily admitted, pregnant, have substance use that interferes with compliance, are not eligible or willing to start clozapine, or refuse procedures like lumbar puncture or MRI are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the findings could help clinicians identify patients who are likely to benefit from clozapine sooner, reducing time on ineffective treatments and improving outcomes.

How similar studies have performed: Previous work has suggested immune and neurochemical differences in some clozapine responders, but existing results are limited and not yet conclusive.

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

Where this trial is running

Glostrup Municipality, Denmark

• Mental Health Services Glostrup, Unit for Complicated Schizophrenia — Glostrup Municipality, Denmark, Denmark (Recruiting)

Study contacts

• Principal investigator: Jimmi Nielsen, PhD — Mental health Service, Glostrup
• Study coordinator: Jimmi Nielsen, PhD

Conditions Schizophrenia; Psychosis