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

NCT ID: NCT05208190

Last Updated: 2026-01-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

280 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-17

Study Completion Date

2028-12-31

Brief Summary

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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

Detailed Description

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This is a single-blind, open-label, randomized, active comparator (TAU) controlled clinical trial to examine the effects of clozapine vs. TAU on the risk for violent acts as measured by the MacArthur Community Violence Interview (MCVI) and to examine the effects of clozapine vs. TAU on the Excitement Factor of the PANSS. Adults age 18-65 with schizophrenia or schizoaffective disorder who have committed a violent act within 6 months and are appropriate for treatment with clozapine or TAU will receive treatment for 24 weeks which will be naturalistically administered. Participants will also participate in assessments and appropriate medical monitoring which will include blood draws, pharmacokinetic blood samples, and physical exams, etc. Cox proportional hazards survival modeling will be used to test the association between treatment group and time until first violent act after randomization (i.e., number of weeks form randomization to violent act).

The NYSPI site is currently paused and has been paused since an institutional pause on human subjects research began in June, 2023. (The IO in concurrence with the IRB paused human subjects research on June 12, 2023. The U.S. Department of Health and Human Services (HHS) Office of Human Research Protections (OHRP) issued an FWA restriction on NYSPI research that also included a pause of human subjects research as of June 23, 2023.) Therefore, the NYSPI site is not enrolling at this time.

Conditions

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Schizophrenia Schizoaffective Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

single-blind, open-label, randomized, active comparator (TAU) controlled clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Blinded raters and a blinded adjudication committee to ensure that the outcome is valid

Study Groups

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Clozapine

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

Group Type EXPERIMENTAL

Clozapine

Intervention Type DRUG

treatment will occur naturalistically, as per standard clinical guidelines

Treatment as usual

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

Group Type ACTIVE_COMPARATOR

treatment as usual

Intervention Type DRUG

naturalistic treatment with any other antipsychotic medication except clozapine

Interventions

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Clozapine

treatment will occur naturalistically, as per standard clinical guidelines

Intervention Type DRUG

treatment as usual

naturalistic treatment with any other antipsychotic medication except clozapine

Intervention Type DRUG

Other Intervention Names

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clozaril

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role lead

Responsible Party

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Ragy Girgis

Professor of Clinical Psychiatry

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ragy Girgis, MD

Role: PRINCIPAL_INVESTIGATOR

New York State Psychiatric Institute

Locations

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University of California, Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

Augusta University Research Institute, Inc.

Augusta, Georgia, United States

Site Status RECRUITING

University of Maryland School of Medicine

Baltimore, Maryland, United States

Site Status RECRUITING

NYU Langone Medical Center

New York, New York, United States

Site Status RECRUITING

New York State Psychiatric Institute

New York, New York, United States

Site Status RECRUITING

Manhattan Psychiatric Center

New York, New York, United States

Site Status RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Ragy Girgis

Role: CONTACT

646-774-5553

Facility Contacts

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Alex Kopelowicz, MD

Role: primary

818-837-8150

Joseph McEvoy, MD

Role: primary

706-792-7021

Deanna Kelly, PharmD

Role: primary

410-402-6861

Donald Goff

Role: primary

646-754-4843

Ragy R Girgis, MD

Role: primary

646-774-5553

Jean-Pierre Lindenmayer, MD

Role: primary

212-249-2720

Fred Jarskog, MD

Role: primary

919-842-7683

Other Identifiers

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1R01MH120317-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

I20-02054

Identifier Type: -

Identifier Source: org_study_id

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