An Exploratory Analysis of Immune and Inflammatory Response Associated With Clozapine

NCT05741502 | Terminated Phase 4 FDA Drug

• 1 other identifier: 2021H0388
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The specific aim of this protocol is to compare Clozapine treatment vs Non-Clozapine antipsychotic treatment in a population of treatment-refractory individuals with schizophrenia. Specifically, it is to test if Clozapine leads to a decrease in levels of inflammatory markers, namely interleukin-6 but with an exploratory view of other markers. Clozapine has superior efficacy and is the only medication approved for treatment-refractory schizophrenia in addition to decreasing the risk of suicidal behavior as well. It is unclear why Clozapine has increased efficacy from a mechanistic viewpoint. We will look at the role of inflammatory markers and assess them 1x along with rating scales for psychosis and suicidality, the other entities which Clozapine has been shown to improve.

Conditions

Treatment-resistant Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Interleukin-6 (IL-6)

  Comparison in interleukin-6 between Clozapine and non-Clozapine group

  Up to 1 year

Secondary Outcomes (3)

• Other immune/cardiac markers

  Up to 1 year

• Positive and Negative Syndrome symptom Scale

  Up to 1 year

• Self-injurious Thoughts and Behaviors Interviews

  Up to 1 year

Study Arms (2)

Clozapine Arm

EXPERIMENTAL

Patients will be on Clozapine for at least 6 months

Drug: Clozapine

Non-Clozapine arm

ACTIVE COMPARATOR

Patients will be on non-Clozapine antipsychotic for at least 6 months

Drug: Antipsychotics,Other (non-Clozapine)

Interventions

Clozapine DRUG

We will assess inflammatory/immune marker labs

Clozapine Arm

Antipsychotics,Other (non-Clozapine) DRUG

We will assess monitor inflammatory/immune marker lab

Also known as: Including Olanzapine, Risperidone, Paliperidone, Quetiapine, Aripiprazole, Ziprasidone, Lurasidone, Cariprazine, and all Typical antipsychotics

Non-Clozapine arm

Eligibility Criteria

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

You may qualify if:

• All participants:
• Between 18 and 65 years of age
• Physically healthy (no clinically significant unstable medical condition as confirmed by medical history and physical examination)
• Able to give informed consent
• Treatment-Refractory Schizophrenia
• Clozapine treatment group (n = 30) Individuals treated with Clozapine consistently for a minimum of 6 months
• Non-Clozapine treatment group Continued treatment with non-Clozapine antipsychotic but would be eligible for Clozapine with the provider/patient electing to not pursue such for clinical reasons, consistently treated for at least 6 months

You may not qualify if:

• Clinically significant medical condition; cardiovascular, pulmonary, endocrine, or renal condition requiring in depth medical treatment
• Active or recent (within 4 weeks) bacterial or viral infection
• Chronic viral infection (hepatitis, HIV)
• History of autoimmune, or chronic inflammatory condition
• Current treatment with lithium
• Treatment with Clozapine in the past 6 months
• Current treatment with immunomodulatory or anti-inflammatory therapy
• Vaccination within the past 3 months
• Current alcohol or substance use disorder of moderate or severe severity
• Intellectual disability (i.e. intelligence quotient \<70)
• Unwilling or unable to sign informed consent document
• Pregnancy
• Any patient deemed ineligible by PI discretion

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

Ohio State University Harding Hospital

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Schizophrenia, Treatment-Resistant

Interventions

Clozapine; Antipsychotic Agents; Risperidone; Paliperidone Palmitate; Quetiapine Fumarate; Aripiprazole; ziprasidone; Lurasidone Hydrochloride; cariprazine

Condition Hierarchy (Ancestors)

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Psychotropic Drugs; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Isoxazoles; Azoles; Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Piperazines; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Thiazoles; Isoindoles

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Clinical Professor

Model Details: Parallel open-label groups of Treatment-Refractory schizophrenia patients treated with Clozapine or non-Clozapine drug

Study Record Dates

• First Submitted: January 20, 2023
• First Posted: February 23, 2023
• Study Start: August 16, 2023
• Primary Completion: January 23, 2026
• Study Completion: January 23, 2026
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)