Striatal Connectivity and Clinical Outcome in Psychosis
|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: NCT02822092|
Recruitment Status : Recruiting
First Posted : July 4, 2016
Last Update Posted : December 3, 2020
|Condition or disease||Intervention/treatment|
|Psychotic Disorders||Drug: Risperidone or Aripiprazole (patients only)|
In this proposed study, the study will examine treatment-related effects on functional brain circuitry in first episode schizophrenia. Converging lines of evidence suggest a key role for striatal disconnectivity in the pathophysiology of psychosis. The proposed study will utilize resting state functional magnetic resonance imaging (rs-fMRI), as well as fMRI tasks derived from the Research Domain Criteria (RDoC) framework, to: 1) develop and validate a prognostic biomarker to predict antipsychotic treatment response; and 2) to model the underlying neural circuitry changes associated with state changes in psychotic symptomatology. As a prognostic biomarker, a neuroimaging assay of striatal connectivity can potentially provide a clinically useful tool to advance the goal of precision medicine. As a longitudinal index of symptom change, our model can serve as an objective index against which to measure potential efficacy of newly developed antipsychotic treatments.
A large, well-characterized cohort of patients presenting with a first episode active psychosis (regardless of DSM diagnosis) will be recruited, along with matched controls. The study will utilize two well-validated fMRI tasks capturing two portions of the positive valence system: probabilistic category learning and reward responsiveness; these tasks are designed to interrogate dorsal and ventral corticostriatal circuits, respectively. The design will be longitudinal, with two scanning sessions performed for each patient: at baseline, and after 12 weeks of treatment. Treatment will be standardized across all patients to reduce potential confounds, and healthy controls will also be scanned at baseline and 12 weeks in order to control for effects of time and practice. Level of psychotic symptomatology (hallucinations, delusions, and thought disorder) will be measured at regular intervals using a comprehensive battery of rating scales. As secondary measures, electroencephalography (EEG) will be performed coinciding with neuroimaging on a subset of patients who provide consent. We will utilize Kaplan-Meier estimators and hierarchical linear modeling to examine the association of baseline striatal connectivity, and changes in connectivity over time, with clinical response of psychotic symptoms to antipsychotic treatment. Deliverables will include both baseline and longitudinal biomarkers that can subsequently be tested in broader, more heterogeneous populations of patients with psychosis.
|Study Type :||Observational|
|Estimated Enrollment :||170 participants|
|Official Title:||Striatal Connectivity and Clinical Outcome in Psychosis|
|Study Start Date :||July 2016|
|Estimated Primary Completion Date :||October 2021|
|Estimated Study Completion Date :||October 2022|
Patients with Psychotic Disorders taking Risp. or Arip.
Risperidone or aripiprazole will be administered. Subjects will start risperidone 1 mg qhs or 5mg qhs aripiprazole; on day 4 the daily dose will be increased to 2 mg risperidone or 10mg aripiprazole and to 3 mg risperidone or 15mg aripiprazole at day 7. The target dose is 3 mg risperidone or 15 mg aripiprazole daily but patients who remain psychotic can be increased to 4 mg risperidone or 20mg aripiprazole at week 4; 5 mg risperidone or 25 mg aripiprazole at week 6 and 6 mg risperidone or 30 mg aripiprazole at week 8. Study Psychiatrists will be able to increase faster if symptoms don't improve as well as decrease for side effects. These dose ranges conform with standard clinical practice and are within the FDA approved dosing ranges for schizophrenia, and schizoaffective disorder. Subjects advance in the risperidone titration schedule until they respond or develop dose-limiting side effects.
Drug: Risperidone or Aripiprazole (patients only)
Inpatients deemed eligible for the study, we be put on open-label risperidone
Healthy Volunteers will participate in MR imaging, Electroencephalogram , and cognitive testing.
- efficacy of risperidone or aripiprazole for psychotic symptoms [ Time Frame: 12 weeks ]To examine the efficacious treatment of psychotic symptoms with either risperidone or aripiprazole measured by specific items on the Brief Psychiatric Rating Scale - conceptual disorganization, grandiosity, hallucinatory behavior, unusual thought content
- Relationship between efficacious treatment of psychotic symptoms and changes in functional connectivity of the striatum [ Time Frame: 12 weeks ]To examine the relationship between efficacious treatment of psychotic symptoms (measured by the Brief Psychiatric Rating Scale) and changes in functional connectivity of the striatum, calculated from fMRI scans
- Predicting treatment efficacy from baseline fMRI scans [ Time Frame: 12 weeks ]To examine whether baseline fMRI scans can predict treatment efficacy which will be measured by the Brief Psychiatric Rating Scale.
Biospecimen Retention: Samples Without DNA
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): NCT02822092
|Contact: Anil Malhotra, MDfirstname.lastname@example.org|
|Contact: Whitney Muscatemail@example.com|
|Principal Investigator:||Anil Malhotra, MD||The Zucker Hillside Hospital|