Biomarker-guided early treatment for schizophrenia
Official title: Biomarkers to Enhance Early Schizophrenia Treatment
Run by Northwell Health · NCT06969755 · Data updated 2026-11-12
This trial tests whether starting clozapine early, based on three biomarkers, helps people aged 18–35 who are having a first episode of psychosis and are likely to not respond to standard antipsychotics but are at low genetic risk for serious side effects.
Quick facts
| Phase | Phase 4 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years to 35 Years |
| Sex | All |
| Enrollment | 180 (estimated) |
| Sponsor | Northwell Health Academic / other |
| Locations | 5 sites (Birmingham, Alabama and 4 other locations) |
| Status | Recruiting |
| Started | September 4, 2024 |
| Main results expected | July 30, 2030 |
| Study ends | July 30, 2030 |
| Registry record updated | July 31, 2026 |
| Trial ID | NCT06969755 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are people aged 18–35 in an early phase of psychosis (≤4 weeks cumulative antipsychotic exposure) with moderate or greater positive symptoms who meet the three biomarker criteria and can give informed consent.
✕Probably not a fit
People who do not meet all three biomarker criteria, who are older than 35, have had more extensive prior antipsychotic treatment, or carry high-risk genotypes for agranulocytosis or weight gain are unlikely to be enrolled or benefit from this specific biomarker-guided intervention.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
Researchers will screen about 410 people with first-episode psychosis across five sites using a resting-state fMRI scan and blood tests for two genetic markers (MC4R and HLA-DQB1). Those who meet all three biomarker criteria (predicted poor response to risperidone/aripiprazole, no high-risk MC4R genotype for weight gain, and no high-risk HLA-DQB1 genotype for agranulocytosis) will be enrolled and receive either early clozapine or standard first-line antipsychotic treatment. The trial compares clinical outcomes between the clozapine group and the standard treatment group to see if biomarker-guided early clozapine improves response. Participants will have follow-up visits and monitoring appropriate for antipsychotic use, including bloodwork and clinical symptom assessments.
Why it matters
Potential benefit: If successful, this approach could allow clinicians to give clozapine earlier to the right patients, improving symptoms and long-term outcomes while reducing the chance of exposing high-risk people to serious side effects.
How similar studies have gone: Clozapine is established as effective for treatment-resistant schizophrenia and individual biomarkers have preliminary supporting data, but using these three biomarkers together to guide early clozapine is a novel approach with limited prior testing.
Who can join: the full rules
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Aged 18 to 35.
2. DSM5 diagnosis (as determined by the SCID5) of schizophrenia, schizoaffective disorder, schizophreniform disorder.
3. Current positive symptoms rated ≥4 (moderate) on one or more of the following BPRS positive subscale items: unusual thought content, conceptual disorganization, hallucinatory behavior, suspiciousness.
4. Preserved striatal connectivity, as determined by screening MRI scan
5. Absence of the MC4R high-risk genotype, as determined by genetic testing
6. Absence of the HLA-DQB1 high-risk genotype, as determined by genetic testing
7. In an early phase of illness as defined by having taken antipsychotic drugs for a cumulative lifetime period of 4 weeks or less (with exceptions of very low doses for other off-label indications, e.g. sleep)
8. Ability to provide informed consent
Exclusion Criteria:
1. The patient reports or medical records state a serious neurological or endocrine disorder at screening that the investigator determines could interfere with the interpretation of the efficacy or safety measurements
2. An abnormal EKG at screening that the investigator determines could interfere with the interpretation of the efficacy or safety measurements
3. Any medical condition which requires treatment with a medication with psychotropic effects.
4. Significant risk of suicidal or homicidal behavior (i.e. 'severe' risk on the Columbia Suicide Scale, a 'hostility' score of 7 on the BPRS, or an answer of 'yes' on questions 4,5 or 6 on the CDSS).
5. Cognitive limitations, or any other factor that would preclude potential participants providing informed consent
6. Contraindications to MRI (e.g. pacemaker).
7. Meeting SCID-5 substance use disorder moderate or severe for any substance, other than nicotine within 3 months of screening visit. Meeting SCID5 substance use disorder mild for any substance other than cannabis, alcohol, or nicotine for less than 3 months prior to screening visit, or a positive urine baseline drug screen with a substance other than nicotine, alcohol, or cannabis
8. Suspected DSM5 intellectual disability based upon clinical interview and psychosocial history, as well as screening with the Weschler Test for Adult Reading (IQ score \<71)
9. Prior psychosurgery
10. Pregnancy (self-report)
11. Seizure disorder (self-report)
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Where it's running
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The University of Alabama at Birmingham
Birmingham, Alabama, United States Recruiting -
University of California San Diego
La Jolla, California, United States Recruiting -
McLean
Belmont, Massachusetts, United States Recruiting -
Feinstein Institute for Medical Research
Glen Oaks, New York, United States Recruiting -
Centre for Addiction and Mental Health
Toronto, Canada Recruiting
Study contacts
- Study coordinator: Patricia Marcy
- Email: pmarcy@northwell.edu
- Phone: 904-302-0811
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.