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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 : March 14, 2017
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Anil K. Malhotra, Northwell Health

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. Patients who present for treatment of a first psychotic episode with a schizophrenia spectrum diagnosis and who are eligible to undergo treatment with risperidone 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.

Condition or disease Intervention/treatment
Psychotic Disorders Drug: Risperidone (patients only)

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
Estimated Enrollment : 170 participants
Observational Model: Case-Only
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine

Drug Information available for: Risperidone
U.S. FDA Resources

Group/Cohort Intervention/treatment
Patients with Psychotic Disorders taking Risperidone
Risperidone will be administered. Subjects will start risperidone 1 mg qhs; on day 4 the daily dose will be increased to 2 mg and to 3 mg at day 7. The target risperidone dose is 3 mg daily but patients who remain psychotic can be increased to 4 mg day at week 4; 5 mg at week 6 and 6 mg 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 (patients only)
Inpatients deemed eligible for the study, we be put on open-label risperidone
Other Name: Risperidal
Healthy Volunteers
Healthy Volunteers will participate in MR imaging, Electroencephalogram , and cognitive testing.

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. 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

  2. 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
Drug Levels

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Healthy Volunteers and Patients with Psychotic Disorders


Inclusion Criteria:

  1. current DSM-IV-defined diagnosis of schizophrenia, schizophreniform, schizoaffective disorder, psychotic disorder NOS, bipolar I (acute manic or mixed episode), major depressive disorder 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, brief psychotic disorder, shared psychotic disorder, or a mood disorder with 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 monotherapy (e.g. neuroleptic malignant syndrome with prior risperidone exposure)
  6. lack of response to a prior adequate trial of risperidone
  7. requires treatment with an antidepressant or mood stabilizing medication

Healthy Volunteers


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


  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

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): NCT02822092

Contact: Anil Malhotra, MD 718-470-8012 amalhotra@northwell.edu
Contact: Noah Weissman 718-470-4152 nweissman@northwell.edu

United States, New York
Zucker Hillside Hospital Recruiting
Glen Oaks, New York, United States, 11004
Contact: Anil Malhotra, MD    718-470-8012    amalhotra@northwell.edu   
Contact: Noah Weissman    7184704152    nweissman@northwell.edu   
Sponsors and Collaborators
Northwell Health
National Institutes of Health (NIH)
Principal Investigator: Anil Malhotra, MD The Zucker Hillside Hospital

Responsible Party: Anil K. Malhotra, Psychiatry Research Department Chair, Northwell Health
ClinicalTrials.gov Identifier: NCT02822092     History of Changes
Other Study ID Numbers: HS16-0411
First Posted: July 4, 2016    Key Record Dates
Last Update Posted: March 14, 2017
Last Verified: March 2017

Additional relevant MeSH terms:
Psychotic Disorders
Mental Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
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
Dopamine Antagonists
Dopamine Agents