NCT05741502

An Exploratory Analysis of Immune and Inflammatory Response Associated With Clozapine

An Exploratory Analysis of Immune and Inflammatory Response Associated With Clozapine Versus Non-Clozapine Antipsychotics in Individuals With Treatment-resistant Schizophrenia

• Status: Terminated
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: Ohio State University · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This study is designed to investigate if treatment with the antipsychotic Clozapine is associated with changes in various immune and inflammatory biomarkers when compared to treatment with non-Clozapine antipsychotic treatments. Clozapine is a uniquely efficacious treatment of psychotic disorders, the only effective agent in approximately 30-40% of individuals with treatment refractory symptoms. Clozapine, unlike other antipsychotic drugs, often precipitates a unique, multi-systemic inflammatory response most widely recognized in the cardiovascular system but also likely the central nervous system (CNS) which is tied into its unique side effect profile but might also account for its increased efficacy. Schizophrenia spectrum disorders affect about 1% of the population with around 30-40% of those diagnosed with symptoms refractory to standard, non-Clozapine antipsychotic treatment. We will measure various inflammatory markers 1x for patients who are stable outpatients. Participants will be patients with treatment-resistant schizophrenia on clozapine treatment for at least 6 months referred from OSU's outpatient clinic with a comparator group also referred from Ohio State University, having shown treatment resistant symptoms but with provider/patient electing not to use clozapine for clinically relevant reasons and have been on antipsychotic medication for at least 6 months. The study includes 1 visit including symptom rating scale assessments and laboratory draw for collection of serum samples and the visit also having more diagnostic assessments to assure proper enrollment. If the study results are positive meaning there is a difference between the two groups, it would help elucidate the potential mechanisms by which Clozapine works and demonstrates increased efficacy for those with treatment-refractory schizophrenia, a severely debilitating, life long illness with marked disability. This would also allow for further studies to explore this mechanism and the role of inflammation and the immune system as well.

Conditions

• Treatment-resistant Schizophrenia

Interventions

Type	Name	Description
DRUG	Clozapine	We will assess inflammatory/immune marker labs
DRUG	Antipsychotics,Other (non-Clozapine)	We will assess monitor inflammatory/immune marker lab

Timeline

• Start date: 2023-08-16
• Primary completion: 2026-01-23
• Completion: 2026-01-23
• First posted: 2023-02-23
• Last updated: 2026-02-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study