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Neural Biomarkers of Clozapine Response

Sponsor
University of Pittsburgh (Other)
Overall Status
Completed
CT.gov ID
NCT03076346
Collaborator
(none)
41
Enrollment
1
Location
40
Actual Duration (Months)
1
Patients Per Site Per Month

Study Details

Study Description

Brief 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 identification of biomarkers that will allow for more efficient use of clozapine, as well as additional treatment targets for patients with refractory illness.

Condition or Disease Intervention/Treatment Phase

    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

    Study Type:
    Observational
    Actual Enrollment :
    41 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Neural Biomarkers of Clozapine Response
    Actual Study Start Date :
    Sep 1, 2017
    Actual Primary Completion Date :
    Dec 31, 2020
    Actual Study Completion Date :
    Dec 31, 2020

    Outcome Measures

    Primary Outcome Measures

    1. Changes in resting state functional connectivity with efficacious clozapine treatment [12 weeks]

      The investigators will examine the functional circuitry associated with a reduction of psychotic symptoms assessed with the Brief Psychiatric Rating Scale.

    Secondary Outcome Measures

    1. Baseline prediction of clozapine response [12 weeks]

      The investigators will use a pattern of baseline functional connectivity to predict successful reduction of psychotic symptoms.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 50 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. 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.

    2. Patient has failed two trials of treatment with antipsychotic drugs and the patient's clinical team is initiating clozapine.

    3. Age of 18 to 50.

    4. Patient is competent and willing to sign informed consent.

    5. For female patients, negative pregnancy test and agreement to use a medically accepted birth control method.

    6. Diagnosis of schizophrenia or schizoaffective disorder

    Exclusion Criteria:

    1. Serious neurological or endocrine disorder.

    2. Any medical condition which requires treatment with a medication with psychotropic effects

    3. Significant risk of suicidal or homicidal behavior

    4. Cognitive or language limitations, or any other factor that would preclude subjects providing informed consent

    5. Contraindications to treatment with clozapine (e.g. failed response in past, or history of adverse reactions to treatment).

    6. Contraindications to magnetic resonance imaging (e.g. pacemaker).

    7. Female patients who are pregnant or breast feeding.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Wpic/Upmc Pittsburgh Pennsylvania United States 15213

    Sponsors and Collaborators

    • University of Pittsburgh

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Deepak Sarpal, MD, University of Pittsburgh
    ClinicalTrials.gov Identifier:
    NCT03076346
    Other Study ID Numbers:
    • PRO16110369
    First Posted:
    Mar 10, 2017
    Last Update Posted:
    Jan 7, 2021
    Last Verified:
    Jan 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Schizophrenia
    Psychotic Disorders

    Study Results

    No Results Posted as of Jan 7, 2021