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Neural Biomarkers of Clozapine Response

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03076346
Recruitment Status : Recruiting
First Posted : March 10, 2017
Last Update Posted : August 19, 2019
Sponsor:
Information provided by (Responsible Party):
Deepak Sarpal, University of Pittsburgh

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
Schizophrenia Treatment-resistant Schizophrenia Schizoaffective Disorder

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.

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Neural Biomarkers of Clozapine Response
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Clozapine




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Baseline prediction of clozapine response [ Time Frame: 12 weeks ]
    The investigators will use a pattern of baseline functional connectivity to predict successful reduction of psychotic symptoms.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with schizophrenia or schizoaffective disorder who have failed treatment with two antipsychotic drugs and are beginning treatment with clozapine.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03076346


Contacts
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Contact: Deepak Sarpal, M.D. 412-246-5618 sarpaldk@upmc.edu

Locations
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United States, Pennsylvania
Wpic/Upmc Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Deepak Sarpal, M.D.         
Sponsors and Collaborators
University of Pittsburgh

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Responsible Party: Deepak Sarpal, MD, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT03076346    
Other Study ID Numbers: PRO16110369
First Posted: March 10, 2017    Key Record Dates
Last Update Posted: August 19, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Schizophrenia
Psychotic Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Clozapine
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
GABA Antagonists
GABA Agents