Recruiting

Clozapine

Sponsor:

New York State Psychiatric Institute

Code:

NCT05208190

Conditions

Schizophrenia

Schizoaffective Disorder

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Clozapine

treatment as usual

Study Details

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

Study ID

NCT05208190

Start date

Mar 17, 2022

Status verified date

Apr, 2026

Completion date

Dec 31, 2028

Anticipated

Primary completion date

Jun 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Design

Enrollment

280 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Clozapine

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

active comparator: Treatment as usual

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

Interventions

Clozapine

treatment will occur naturalistically, as per standard clinical guidelines

treatment as usual

naturalistic treatment with any other antipsychotic medication except clozapine

Primary outcome measure

  • Effectiveness outcome: Violent acts [ Time Frame: Time to violent act from randomization to treatment completion (24 weeks) ]
  • Target engagement outcome: Excitement Factor of the Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Randomization to end of study treatment (24 weeks) ]

Central Contacts and Locations

Central contacts

Ragy Girgis

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

Locations

University of California, Los Angeles

Recruiting

Los Angeles, California, United States, 90024

Contacts

Alex Kopelowicz, MD

818-837-8150akopel@ucla.edu

Augusta University Research Institute, Inc.

Recruiting

Augusta, Georgia, United States, 30912

Contacts

Joseph McEvoy, MD

706-792-7021jmcevoy@augusta.edu

University of Maryland School of Medicine

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Deanna Kelly, PharmD

410-402-6861dlkelly@som.umaryland.edu

NYU Langone Medical Center

Recruiting

New York, New York, United States, 10016

Contacts

Donald Goff

646-754-4843donald.goff@nyulangone.org

New York State Psychiatric Institute

Recruiting

New York, New York, United States, 10032

Contacts

Ragy R Girgis, MD

646-774-5553rg2290@columbia.edu

Principal Investigator:

Ragy R Girgis, MD

Manhattan Psychiatric Center

Recruiting

New York, New York, United States, 10035

Contacts

Jean-Pierre Lindenmayer, MD

212-249-2720jean-pierre.lindenmayer@nki.rfmh.org

University of North Carolina at Chapel Hill

Recruiting

Chapel Hill, North Carolina, United States, 27599

Contacts

Fred Jarskog, MD

919-842-7683jarskog@med.unc.edu

More Information

Sponsor

New York State Psychiatric Institute

Last update posted

May 4, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by New York State Psychiatric Institute on 2026-05-04.