Treatment-resistant SchizophreniaPhase 4NCT05741502
An Exploratory Analysis of Immune and Inflammatory Response Associated With Clozapine
A Phase 4 study testing Clozapine and Antipsychotics,Other (non-Clozapine) in people with Treatment-resistant Schizophrenia, run by Ohio State University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Treatment-resistant Schizophrenia
- What is being tested?
- Clozapine and Antipsychotics,Other (non-Clozapine)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Aug 2023to 23 Jan 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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 locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Harding Hospital
Columbus, Ohio, 43210
About this study
Official title: An Exploratory Analysis of Immune and Inflammatory Response Associated With Clozapine Versus Non-Clozapine Antipsychotics in Individuals With Treatment-resistant Schizophrenia
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.
Read the 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
- Being tested
- Clozapine, Antipsychotics,Other (non-Clozapine)
- Medical subject headings
- Schizophrenia, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClozapineDrug
We will assess inflammatory/immune marker labs
Antipsychotics,Other (non-Clozapine)Drug
Also called Including Olanzapine, Risperidone, Paliperidone, Quetiapine, Aripiprazole, Ziprasidone, Lurasidone, Cariprazine, and all Typical antipsychotics
We will assess monitor inflammatory/immune marker lab
| Study group | Role | What they receive |
|---|---|---|
| Clozapine Arm | Experimental | Patients will be on Clozapine for at least 6 months Receives: Drug: Clozapine |
| Non-Clozapine arm | Active comparator | Patients will be on non-Clozapine antipsychotic for at least 6 months Receives: Drug: Antipsychotics,Other (non-Clozapine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Interleukin-6 (IL-6)
Comparison in interleukin-6 between Clozapine and non-Clozapine group
Measured: Up to 1 year
Secondary outcomes (3)
Other immune/cardiac markers
Comparison in hsCRP, interleukin-1β, interferon-γ, transforming growth factor-β, tumor necrosis factor between Clozapine and non-Clozapine group
Measured: Up to 1 year
Positive and Negative Syndrome symptom Scale
Comparison in psychosis rating scales (PANSS) between Clozapine and non-Clozapine group. Higher scores indicate more severe symptoms of psychosis. Score from 30-210
Measured: Up to 1 year
Self-injurious Thoughts and Behaviors Interviews
Comparison between Clozapine and non-Clozapine group in Suicidality rating scales. Scores on rating will be binary (yes/no) for suicidal ideation and also suicide attempts.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2023
- Study start16 Aug 2023
- Primary completion23 Jan 2026
- Study completion23 Jan 2026
Why it stopped: Not able to recruit enough subjects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment-resistant SchizophreniaStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Parallel open-label groups of Treatment-Refractory schizophrenia patients treated with Clozapine or non-Clozapine drug
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Walter Stearns, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05741502
- Sponsor's protocol ID
- 2021H0388
- Status last verified
- Feb 2026
- First submitted
- 20 Jan 2023
- Last updated
- 25 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Analysis of Immune and Inflammatory Response Associated With Clozapine Versus Non-Clozapine Antipsychotics in Individuals With Treatment-resistant Schizophrenia
- ClinicalTrials.gov ID
- NCT05741502
- Acronym / sponsor ID
- 2021H0388
- Conditions
- Treatment-resistant Schizophrenia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Not able to recruit enough subjects
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Study start
- 16 Aug 2023 (actual)
- Primary completion
- 23 Jan 2026 (actual)
- Study completion
- 23 Jan 2026 (actual)
- First posted
- 23 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Parallel open-label groups of Treatment-Refractory schizophrenia patients treated with Clozapine or non-Clozapine drug
| Arm | Type | Receives |
|---|---|---|
| Clozapine Arm | Experimental | Drug: ClozapinePatients will be on Clozapine for at least 6 months |
| Non-Clozapine arm | Active comparator | Drug: Antipsychotics,Other (non-Clozapine)Patients will be on non-Clozapine antipsychotic for at least 6 months |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- All participants:
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClozapineWe will assess inflammatory/immune marker labs | Drug | Clozapine Arm |
| Antipsychotics,Other (non-Clozapine)Also: Including Olanzapine, Risperidone, Paliperidone, Quetiapine, Aripiprazole, Ziprasidone, Lurasidone, Cariprazine, and all Typical antipsychoticsWe will assess monitor inflammatory/immune marker lab | Drug | Non-Clozapine arm |
Primary outcome
Interleukin-6 (IL-6)
Time frame: Up to 1 year
Comparison in interleukin-6 between Clozapine and non-Clozapine group
3 secondary outcomes
Other immune/cardiac markers
Time frame: Up to 1 year
Positive and Negative Syndrome symptom Scale
Time frame: Up to 1 year
Self-injurious Thoughts and Behaviors Interviews
Time frame: Up to 1 year
Results and safety
The study was stopped early (reason given: Not able to recruit enough subjects). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clozapine and Antipsychotics,Other (non-Clozapine) in people with Treatment-resistant Schizophrenia, run by Ohio State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Not able to recruit enough subjects). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Interleukin-6 (IL-6) (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2026.