Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial

NCT05208190 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: I20-020541R01MH120317-01A1
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 7

Brief Summary

Two-hundred and eighty individuals with schizophrenia who have a recent history of violent acts will be randomized in this 2-arm, parallel-group, 24-week, open-label, 7-site clinical trial to examine the effects of treatment with clozapine vs antipsychotic treatment as usual (TAU) for reducing the risk of violent acts in real-world settings

Conditions

Schizophrenia; Schizoaffective Disorder

Outcome Measures

Primary Outcomes (2)

• Effectiveness outcome: Violent acts

  violent acts as measured by the MacArthur Community Violence Interview

  Time to violent act from randomization to treatment completion (24 weeks)

• Target engagement outcome: Excitement Factor of the Positive and Negative Syndrome Scale (PANSS)

  a composite of the scores of excitement, uncooperativeness, poor impulse control, and hostility)

  Randomization to end of study treatment (24 weeks)

Secondary Outcomes (2)

• Effect on aggression

  Randomization to end of treatment (24 weeks)

• Positive symptoms and substance use

  Randomization to end of treatment (24 weeks)

Other Outcomes (1)

• Interventions to Prevent Violence

  Randomization to end of treatment (24 weeks)

Study Arms (2)

Clozapine

EXPERIMENTAL

treatment with clozapine naturalistically administered (as per clinical guideline).

Drug: Clozapine

Treatment as usual

ACTIVE COMPARATOR

open label naturalistic treatment as usual with any antipsychotic other than clozapine

Drug: treatment as usual

Interventions

Clozapine DRUG

treatment will occur naturalistically, as per standard clinical guidelines

Also known as: clozaril

Clozapine

treatment as usual DRUG

naturalistic treatment with any other antipsychotic medication except clozapine

Treatment as usual

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnostic and Statistical Manual-5 (DSM-5) diagnosis of schizophrenia or schizoaffective disorder by the Structured Clinical Interview for DSM-5 (SCID-5)
• commission of a minor or serious act of violence as measured by the MCVI in the last six months
• willing and able to provide informed consent
• medically stable in judgment of physician providing study treatment
• appropriate for treatment with either clozapine or TAU, i.e., that there is clinical equipoise between the two treatment options. Individuals who are currently medication free or on any antipsychotic, with the exception of clozapine or long-acting injectable medication with a dosing interval of more than 30 days will be eligible

You may not qualify if:

• An unstable of serious medical or neurological condition including a myeloproliferative disorder or condition that surprises the bone marrow
• A history of intolerance/allergy to clozapine (e.g., agranulocytosis, small bowel obstruction, or myocarditis)
• A history of intellectual impairment
• pregnant or lactating women; women who are able to become pregnant but who are not willing to sue effective methods of birth control
• Individuals who score a 3, 4, or 5 within the previous month on the suicidal ideation section of the Columbia Suicide Severity Rating Scale (CSSRS), have any suicidal behavior (not including Not Suicidal Self Injury) within the previous 3 months, or are, in the opinion of the investigator, at too high of a risk for suicide to be safety treated in a randomized trial in which they may not be treated with clozapine
• Documented intolerance to or lack of any therapeutic benefit with clozapine after a full trial

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (7)

University of California, Los Angeles

Los Angeles, California, 90024, United States

RECRUITING

Augusta University Research Institute, Inc.

Augusta, Georgia, 30912, United States

RECRUITING

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

RECRUITING

NYU Langone Medical Center

New York, New York, 10016, United States

RECRUITING

New York State Psychiatric Institute

New York, New York, 10032, United States

RECRUITING

Manhattan Psychiatric Center

New York, New York, 10035, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Clozapine; Therapeutics

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ragy Girgis, MD

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ragy Girgis

CONTACT

646-774-5553; ragy.girgis@nyspi.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded raters and a blinded adjudication committee to ensure that the outcome is valid
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Psychiatry

Model Details: single-blind, open-label, randomized, active comparator (TAU) controlled clinical trial

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: January 26, 2022
• Study Start: March 17, 2022
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

US (7)