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Striatal Connectivity and Clinical Outcome in Psychosis

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ClinicalTrials.gov Identifier: NCT02822092
Recruitment Status : Recruiting
First Posted : July 4, 2016
Last Update Posted : December 3, 2020
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Anil K. Malhotra, Northwell Health

Tracking Information
First Submitted Date June 27, 2016
First Posted Date July 4, 2016
Last Update Posted Date December 3, 2020
Study Start Date July 2016
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 15, 2019)
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
Original Primary Outcome Measures
 (submitted: June 29, 2016)
efficacy of risperidone for psychotic symptoms [ Time Frame: 12 weeks ]
To examine the efficacious treatment of psychotic symptoms with risperidone measured by specific items on the Brief Psychiatric Rating Scale - conceptual disorganization, grandiosity, hallucinatory behavior, unusual thought content
Change History
Current Secondary Outcome Measures
 (submitted: June 29, 2016)
  • 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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Striatal Connectivity and Clinical Outcome in Psychosis
Official Title Striatal Connectivity and Clinical Outcome in Psychosis
Brief Summary This is an observational neuroimaging treatment study. This study involves examining the neural circuitry of controlled treatment of patients presenting with a first-episode of psychosis with risperidone or aripiprazole. Patients who present for treatment of a first psychotic episode with a schizophrenia spectrum diagnosis and who are eligible to undergo treatment with either risperidone or aripiprazole will be offered participation in the study. Clinical ratings, neuropsychological testing, neuroimaging and EEG will be conducted at baseline. Additionally, subjects will undergo the same assessments at week 12 to determine treatment-related biomarkers. Clinical ratings, including neurocognitive testing, will be conducted by blinded raters at study visits during treatment. Healthy controls (N=50) will also be recruited and scanned twice (12-week interval) to control for effects of time and practice.
Detailed Description

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
Study Design Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Drug Levels
Sampling Method Non-Probability Sample
Study Population Healthy Volunteers and Patients with Psychotic Disorders
Condition Psychotic Disorders
Intervention Drug: Risperidone or Aripiprazole (patients only)
Inpatients deemed eligible for the study, we be put on open-label risperidone
Other Names:
  • Risperidal
  • Aripiprazole
Study Groups/Cohorts
  • 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.
    Intervention: Drug: Risperidone or Aripiprazole (patients only)
  • Healthy Volunteers
    Healthy Volunteers will participate in MR imaging, Electroencephalogram , and cognitive testing.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: June 29, 2016)
170
Original Estimated Enrollment Same as current
Estimated Study Completion Date October 2022
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Patients

Inclusion Criteria:

  1. current DSM-IV-defined diagnosis of schizophrenia, schizophreniform, schizoaffective disorder, brief psychotic disorder, psychotic disorder NOS, bipolar I with psychotic features (acute manic or mixed episode), major depressive disorder with psychotic features as assessed using the Structured Clinical Interview for Axis I DSM-IV Disorders (SCID-I/P) (First et al, 1994);
  2. does not meet DSM-IV criteria for a current substance-induced psychotic disorder, a psychotic disorder due to a general medical condition, delusional disorder, shared psychotic disorder, or a mood disorder without psychotic features;
  3. current positive symptoms rated ≥4 (moderate) on one or more of these BPRS (Woerner et al., 1988) items: conceptual disorganization, grandiosity, hallucinatory behavior, unusual thought content;
  4. is in a early phase of illness as defined by having taken antipsychotic medications for a cumulative lifetime period of 4 weeks or less,
  5. age 15 to 40;
  6. competent and willing to sign informed consent; and
  7. for women, negative pregnancy test and agreement to use a medically accepted birth control method.

Exclusion Criteria:

  1. serious neurological or endocrine disorder or any medical condition or treatment known to affect the brain
  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. medical contraindications to treatment with risperidone or aripiprazole monotherapy (e.g. neuroleptic malignant syndrome with prior risperidone exposure)
  6. lack of response to a prior adequate trial of risperidone or aripiprazole

Healthy Volunteers

Inclusion

  1. age 15 to 40
  2. competent to sign informed consent

Exclusion

  1. lifetime history of any mood disorder or any psychotic disorder as determined by clinical interview using the SCID-NP
  2. MR imaging contraindications
  3. neurologic conditions
  4. any serious non-psychiatric disorder that could affect brain functioning
  5. mental retardation
Sex/Gender
Sexes Eligible for Study: All
Ages 15 Years to 40 Years   (Child, Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Anil Malhotra, MD 718-470-8012 amalhotra@northwell.edu
Contact: Whitney Muscat 718-470-4152 wmuscat@northwell.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02822092
Other Study ID Numbers HS16-0411
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Anil K. Malhotra, Northwell Health
Study Sponsor Northwell Health
Collaborators National Institutes of Health (NIH)
Investigators
Principal Investigator: Anil Malhotra, MD The Zucker Hillside Hospital
PRS Account Northwell Health
Verification Date December 2020