An Exploratory Analysis of Immune and Inflammatory Response Associated with Clozapine

The Ohio State University

Status and phase: Enrolling; Phase 4

Conditions: Treatment-resistant Schizophrenia

Treatments: Drug: Clozapine; Drug: Antipsychotics,Other (non-Clozapine)

Study type: Interventional

Funder types: Other

Identifiers

NCT05741502

2021H0388

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Clozapine Arm

Experimental group

Description:

Patients will be on Clozapine for at least 6 months

Treatment:

Drug: Clozapine

Non-Clozapine arm

Active Comparator group

Description:

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

Treatment:

Drug: Antipsychotics,Other (non-Clozapine)