Clinical trial NCT05208190: Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial
Official title: Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Schizophrenia
Schizoaffective Disorder
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2022-01-26
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: single-blind, open-label, randomized, active comparator (TAU) controlled clinical trial
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Effectiveness outcome: Violent acts
timeFrame: Time to violent act from randomization to treatment completion (24 weeks)
measure: Target engagement outcome: Excitement Factor of the Positive and Negative Syndrome Scale (PANSS)
timeFrame: Randomization to end of study treatment (24 weeks)
Secondary outcomes:
measure: Effect on aggression
timeFrame: Randomization to end of treatment (24 weeks)
measure: Positive symptoms and substance use
timeFrame: Randomization to end of treatment (24 weeks)
Other outcomes:
measure: Interventions to Prevent Violence
timeFrame: Randomization to end of treatment (24 weeks)
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Augusta
country: United States
facility: Augusta University Research Institute, Inc.
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
city: New York
country: United States
facility: Manhattan Psychiatric Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: New York State Psychiatric Institute
name: Ragy Girgis, MD
role: PRINCIPAL_INVESTIGATOR
References: