SchizophreniaNCT03076346
Neural Biomarkers of Clozapine Response
An observational study of Schizophrenia and Treatment-resistant Schizophrenia, run by University of Pittsburgh at 1 site in United States.
Trial summary
Clozapine has consistently shown to be a superior drug for psychosis in patients who do not respond to other treatments, but its mechanism of action remains unknown. The overall goal of this study is to examine the functional neural circuitry that underlies successful treatment with clozapine, which may lead to the… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Schizophrenia, Treatment-resistant Schizophrenia, Schizoaffective Disorder
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2017to 31 Dec 2020
- Phase
- Observational
- 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 50 years
- All sexes
- No healthy volunteers
- Adult
Study population: Patients with schizophrenia or schizoaffective disorder who have failed treatment with two antipsychotic drugs and are beginning treatment with clozapine.
Who may be able to join
- Current positive symptoms rated ≥4 (moderate) on one or more of these Brief Psychiatric Rating Scale items: hallucinatory behavior, unusual thought content and conceptual disorganization.
- Patient has failed two trials of treatment with antipsychotic drugs and the patient's clinical team is initiating clozapine.
- Age of 18 to 50.
- Patient is competent and willing to sign informed consent.
- For female patients, negative pregnancy test and agreement to use a medically accepted birth control method.
- Diagnosis of schizophrenia or schizoaffective disorder
Who cannot join
- Serious neurological or endocrine disorder.
- Any medical condition which requires treatment with a medication with psychotropic effects
- Significant risk of suicidal or homicidal behavior
- Cognitive or language limitations, or any other factor that would preclude subjects providing informed consent
- Contraindications to treatment with clozapine (e.g. failed response in past, or history of adverse reactions to treatment).
- Contraindications to magnetic resonance imaging (e.g. pacemaker).
- Female patients who are pregnant or breast feeding.
Trial locations and contacts
1 site in 1 country.
About this study
Clozapine has consistently shown to be a superior drug for psychosis in patients who do not respond to other treatments, but its mechanism of action remains unknown. The overall goal of this study is to examine the functional neural circuitry that underlies successful treatment with clozapine, which may lead to the identification of biomarkers that will allow for more efficient use of clozapine, as well as additional treatment targets for patients with refractory illness.
Read the detailed description
A large number of patients with chronic psychotic disorders continue to have symptoms following unsuccessful trials with first-line antipsychotic drugs. For these patients with refractory psychosis, clozapine has consistently demonstrated superior efficacy. Clozapine is often underutilized and administered late in a patient's course of treatment, which leads to increased morbidity, unnecessary medication trials, and increased health care expenditure. Meanwhile, the mechanism of action underlying clozapine's novel effects remains unknown and has not been studied with modern neuroimaging methods. Identifying the neural mechanisms by which clozapine exerts its effects may lead to biomarkers that will facilitate efficient utilization of the drug, and introduce novel treatment targets. In patients with refractory psychotic symptoms, the proposed study will use resting-state and task-based functional MRI (fMRI) to examine the neural circuitry of efficacious treatment with a trial of clozapine. Patients will undergo fMRI scanning both before and after 12 weeks of treatment, with the aims of determining: baseline patterns of resting-state functional connectivity and task-based activation that predict response to treatment; and changes in resting-state and task-based functional circuitry associated with efficacious treatment. Results of this proposal may lead to biomarkers that will optimize treatment algorithms for psychotic disorders and facilitate drug development for refractory psychosis.
- Medical subject headings
- Schizophrenia, Schizophrenia, Treatment-Resistant, Psychotic Disorders
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in resting state functional connectivity with efficacious clozapine treatment
The investigators will examine the functional circuitry associated with a reduction of psychotic symptoms assessed with the Brief Psychiatric Rating Scale.
Measured: 12 weeks
Secondary outcomes (1)
Baseline prediction of clozapine response
The investigators will use a pattern of baseline functional connectivity to predict successful reduction of psychotic symptoms.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2017
- Study start1 Sep 2017
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Deepak K. Sarpal, M.D., University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03076346
- Sponsor's protocol ID
- STUDY19060115
- Status last verified
- Mar 2025
- First submitted
- 6 Mar 2017
- Last updated
- 6 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Biomarkers of Clozapine Response
- ClinicalTrials.gov ID
- NCT03076346
- Acronym / sponsor ID
- STUDY19060115
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Study start
- 1 Sep 2017 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 10 Mar 2017 (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.
Clozapine has consistently shown to be a superior drug for psychosis in patients who do not respond to other treatments, but its mechanism of action remains unknown. The overall goal of this study is to examine the functional neural circuitry that underlies successful treatment with clozapine, which may lead to the identification of biomarkers that will allow for more efficient use of clozapine, as well as additional treatment targets for patients with refractory illness.
Detailed description
A large number of patients with chronic psychotic disorders continue to have symptoms following unsuccessful trials with first-line antipsychotic drugs. For these patients with refractory psychosis, clozapine has consistently demonstrated superior efficacy. Clozapine is often underutilized and administered late in a patient's course of treatment, which leads to increased morbidity, unnecessary medication trials, and increased health care expenditure. Meanwhile, the mechanism of action underlying clozapine's novel effects remains unknown and has not been studied with modern neuroimaging methods. Identifying the neural mechanisms by which clozapine exerts its effects may lead to biomarkers that will facilitate efficient utilization of the drug, and introduce novel treatment targets. In patients with refractory psychotic symptoms, the proposed study will use resting-state and task-based functional MRI (fMRI) to examine the neural circuitry of efficacious treatment with a trial of clozapine. Patients will undergo fMRI scanning both before and after 12 weeks of treatment, with the aims of determining: baseline patterns of resting-state functional connectivity and task-based activation that predict response to treatment; and changes in resting-state and task-based functional circuitry associated with efficacious treatment. Results of this proposal may lead to biomarkers that will optimize treatment algorithms for psychotic disorders and facilitate drug development for refractory psychosis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Patients with schizophrenia or schizoaffective disorder who have failed treatment with two antipsychotic drugs and are beginning treatment with clozapine.
Key inclusion criteria (6 listed)
- Current positive symptoms rated ≥4 (moderate) on one or more of these Brief Psychiatric Rating Scale items: hallucinatory behavior, unusual thought content and conceptual disorganization.
- Patient has failed two trials of treatment with antipsychotic drugs and the patient's clinical team is initiating clozapine.
- Age of 18 to 50.
- Patient is competent and willing to sign informed consent.
- For female patients, negative pregnancy test and agreement to use a medically accepted birth control method.
Key exclusion criteria (7 listed)
- Serious neurological or endocrine disorder.
- Any medical condition which requires treatment with a medication with psychotropic effects
- Significant risk of suicidal or homicidal behavior
- Cognitive or language limitations, or any other factor that would preclude subjects providing informed consent
- Contraindications to treatment with clozapine (e.g. failed response in past, or history of adverse reactions to treatment).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Changes in resting state functional connectivity with efficacious clozapine treatment
Time frame: 12 weeks
The investigators will examine the functional circuitry associated with a reduction of psychotic symptoms assessed with the Brief Psychiatric Rating Scale.
1 secondary outcome
Baseline prediction of clozapine response
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2025.
- 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?
An observational study of Schizophrenia and Treatment-resistant Schizophrenia, run by University of Pittsburgh 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 6 inclusion and 7 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: finished, as of the sponsor's last update on 6 Mar 2025. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Changes in resting state functional connectivity with efficacious clozapine treatment (time frame: 12 weeks). 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 6 Mar 2025; AzTrials last refreshed its copy on 7 Nov 2026.