Schizophenia DisorderPhase 4BEESTNCT06969755
Biomarkers to Enhance Early Schizophrenia Treatment
A Phase 4 study testing aripiprazole, risperidone and clozapine in people with Schizophenia Disorder, run by Northwell Health at 5 sites in 2 countries.
Trial summary
This study is recruiting participants who are experiencing a first episode of psychosis and who have certain genetic factors that may make them respond better to certain medications that are used to treat people with psychosis. Read more about this study
- Who is it for?
- Ages 18 to 35 years
- Conditions the study is for
- Schizophenia Disorder
- What is being tested?
- aripiprazole, risperidone and clozapine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 4 Sep 2024to 30 Jul 2030
- 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 35 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Aged 18 to 35.
- DSM5 diagnosis (as determined by the SCID5) of schizophrenia, schizoaffective disorder, schizophreniform disorder.
- 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.
- Preserved striatal connectivity, as determined by screening MRI scan
- Absence of the MC4R high-risk genotype, as determined by genetic testing
- Absence of the HLA-DQB1 high-risk genotype, as determined by genetic testing
- 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)
- Ability to provide informed consent
Who cannot join
- 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
- An abnormal EKG at screening that the investigator determines could interfere with the interpretation of the efficacy or safety measurements
- Any medical condition which requires treatment with a medication with psychotropic effects.
- 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).
- Cognitive limitations, or any other factor that would preclude potential participants providing informed consent
- Contraindications to MRI (e.g. pacemaker).
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- 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
- 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)
- Prior psychosurgery
- Pregnancy (self-report)
- Seizure disorder (self-report)
- -
Trial locations and contacts
5 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
5 sites in 2 countries
United States4 sites, 4 recruiting
- Recruiting
McLean
Belmont, Massachusetts, 02478
Dost Ongur, 617-855-3922, dongur@mgb.org
- Recruiting
The University of Alabama at Birmingham
Birmingham, Alabama, 35294
Adrienne Lahti, MD, 205-996-6171, alahti@uabmc.com
- Recruiting
Feinstein Institute for Medical Research
Glen Oaks, New York, 11004
Taylor Marzouk Coordinator, 718-470-8905, tmarzouk@northwell.edu
- Recruiting
University of California San Diego
La Jolla, California, 92093
Cherine Akkarine, 909-589-4678, carelab@health.ucsd.edu
Canada1 site, 1 recruiting
- Recruiting
Centre for Addiction and Mental Health
Toronto
Kathleen Tremells, Tel. 416-535-8501 | Ext. 33937, kathleen.tremells@camh.ca
About this study
This study is recruiting participants who are experiencing a first episode of psychosis and who have certain genetic factors that may make them respond better to certain medications that are used to treat people with psychosis.
Read the detailed description
The study is designed to test the hypothesis that, compared with standard treatment with FL-APs (risperidone or aripiprazole), early treatment with clozapine (CLZ) will benefit patients in the first episode of psychosis (FEP) who have been designated three biomarker positive (3B+) as follows: 1) likely to have a poor response to FL-APs; 2) not at heightened risk for clozapine-induced agranulocytosis and 3) not at heightened risk for antipsychotic-induced weight gain. The study will recruit n=410 FEP across the 5 participating sites for screening on each of the 3 biomarkers (striatal connectivity in relation to risk of treatment response/resistance to conventional antipsychotics, MC4R genotype in relation to weight gain risk, and HLA-DQB1 genotype in relation to agranulocytosis risk), which involves a rs-fMRI scan (for response/non-response prediction) and a blood draw for genotyping per above (to screen for heightened risk for each of the two side effects). Those failing to meet any of the 3 biomarker criteria will receive FEP care but will not be enrolled in the study.
- Conditions
- Schizophenia Disorder
- Being tested
- aripiprazole, risperidone, clozapine
- Keywords
- Schizophrenia
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aripiprazoleDrug
aripiprazole arm (titrated dose)
risperidoneDrug
risperidone arm (titrated dose)
clozapineDrug
clozapine (titrated dose)
| Study group | Role | What they receive |
|---|---|---|
| risperidone | Active comparator | risperidone treatment provided per protocol Receives: Drug: risperidone |
| aripiprazole | Active comparator | aripiprazole treatment per protocol Receives: Drug: aripiprazole |
| clozapine | Active comparator | clozapine treatment per protocol Receives: Drug: clozapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total change in BPRS Symptoms
To compare the 12-week response rate of CLZ versus FL-APs (both risperidone and aripiprazole) utilizing the BPRS
Measured: 12 weeks
Secondary outcomes (3)
Weight Gain
To compare weight gain associated with 12 weeks of treatment with CLZ vs. FL-APs in 3B+ FEP patients.
Measured: 12 weeks
Agranulocytosis
To compare rates of agranulocytosis in 3B+ FEP patients treated for 12 weeks with CLZ vs. 3B+ FEP patients treated with FL-APs
Measured: 12 weeks
Neutropenia
To compare rates of neutropenia in 3B+ FEP patients treated for 12 weeks with CLZ vs. 3B+ FEP patients treated with FL-APs
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2025
- Study start4 Sep 2024
- Primary completion30 Jul 2030 (estimated)
- Study completion30 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Schizophenia DisorderStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06969755
- Sponsor's protocol ID
- BEEST
- Other IDs
- 1R01MH134883-01A1
- Acronym
- BEEST
- Status last verified
- Jul 2026
- First submitted
- 4 Apr 2025
- Last updated
- 31 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All de-identified data will be placed in the NDA.
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers to Enhance Early Schizophrenia Treatment
- ClinicalTrials.gov ID
- NCT06969755
- Acronym / sponsor ID
- BEEST / BEEST
- Conditions
- Schizophenia Disorder
- Keywords
- Schizophrenia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 4 Sep 2024 (actual)
- Primary completion
- 30 Jul 2030 (estimated)
- Study completion
- 30 Jul 2030 (estimated)
- First posted
- 14 May 2025 (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.
This study is recruiting participants who are experiencing a first episode of psychosis and who have certain genetic factors that may make them respond better to certain medications that are used to treat people with psychosis.
Detailed description
The study is designed to test the hypothesis that, compared with standard treatment with FL-APs (risperidone or aripiprazole), early treatment with clozapine (CLZ) will benefit patients in the first episode of psychosis (FEP) who have been designated three biomarker positive (3B+) as follows: 1) likely to have a poor response to FL-APs; 2) not at heightened risk for clozapine-induced agranulocytosis and 3) not at heightened risk for antipsychotic-induced weight gain. The study will recruit n=410 FEP across the 5 participating sites for screening on each of the 3 biomarkers (striatal connectivity in relation to risk of treatment response/resistance to conventional antipsychotics, MC4R genotype in relation to weight gain risk, and HLA-DQB1 genotype in relation to agranulocytosis risk), which involves a rs-fMRI scan (for response/non-response prediction) and a blood draw for genotyping per above (to screen for heightened risk for each of the two side effects). Those failing to meet any of the 3 biomarker criteria will receive FEP care but will not be enrolled in the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| risperidone | Active comparator | Drug: risperidonerisperidone treatment provided per protocol |
| aripiprazole | Active comparator | Drug: aripiprazolearipiprazole treatment per protocol |
| clozapine | Active comparator | Drug: clozapineclozapine treatment per protocol |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Aged 18 to 35.
- DSM5 diagnosis (as determined by the SCID5) of schizophrenia, schizoaffective disorder, schizophreniform disorder.
- 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.
- Preserved striatal connectivity, as determined by screening MRI scan
- Absence of the MC4R high-risk genotype, as determined by genetic testing
Key exclusion criteria (12 listed)
- 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
- An abnormal EKG at screening that the investigator determines could interfere with the interpretation of the efficacy or safety measurements
- Any medical condition which requires treatment with a medication with psychotropic effects.
- 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).
- Cognitive limitations, or any other factor that would preclude potential participants providing informed consent
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 |
|---|---|---|
| aripiprazolearipiprazole arm (titrated dose) | Drug | aripiprazole |
| risperidonerisperidone arm (titrated dose) | Drug | risperidone |
| clozapineclozapine (titrated dose) | Drug | clozapine |
Primary outcome
Total change in BPRS Symptoms
Time frame: 12 weeks
To compare the 12-week response rate of CLZ versus FL-APs (both risperidone and aripiprazole) utilizing the BPRS
3 secondary outcomes
Weight Gain
Time frame: 12 weeks
Agranulocytosis
Time frame: 12 weeks
Neutropenia
Time frame: 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 31 Jul 2026.
- Individual participant dataSharing planned: Yes. All de-identified data will be placed in the NDA.
Related trials for Schizophenia Disorder
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Profiling Vulnerability and Resilience for Mental Illness Following Viral Infections: Translating Epidemiology to Deep-phenotyping.
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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.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing aripiprazole, risperidone and clozapine in people with Schizophenia Disorder, run by Northwell Health at 5 sites in 2 countries.
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 8 inclusion and 12 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 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Canada. 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 Patricia Marcy (904-302-0811, pmarcy@northwell.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total change in BPRS Symptoms (time frame: 12 weeks). 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 31 Jul 2026; AzTrials last refreshed its copy on 7 Nov 2026.