- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02822092
Striatal Connectivity and Clinical Outcome in Psychosis
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Contacts and Locations
Study Contact
- Name: Anil Malhotra, MD
- Phone Number: 718-470-8012
- Email: amalhotra@northwell.edu
Study Contact Backup
- Name: Whitney Muscat
- Phone Number: 718-470-4152
- Email: wmuscat@northwell.edu
Study Locations
-
-
New York
-
Glen Oaks, New York, United States, 11004
- Zucker Hillside Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Patients
Inclusion Criteria:
- 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);
- 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;
- 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;
- is in a early phase of illness as defined by having taken antipsychotic medications for a cumulative lifetime period of 4 weeks or less,
- age 15 to 40;
- competent and willing to sign informed consent; and
- for women, negative pregnancy test and agreement to use a medically accepted birth control method.
Exclusion Criteria:
- serious neurological or endocrine disorder or any medical condition or treatment known to affect the brain
- any medical condition which requires treatment with a medication with psychotropic effects
- significant risk of suicidal or homicidal behavior
- cognitive or language limitations, or any other factor that would preclude subjects providing informed consent
- medical contraindications to treatment with risperidone or aripiprazole monotherapy (e.g. neuroleptic malignant syndrome with prior risperidone exposure)
- lack of response to a prior adequate trial of risperidone or aripiprazole
Healthy Volunteers
Inclusion
- age 15 to 40
- competent to sign informed consent
Exclusion
- lifetime history of any mood disorder or any psychotic disorder as determined by clinical interview using the SCID-NP
- MR imaging contraindications
- neurologic conditions
- any serious non-psychiatric disorder that could affect brain functioning
- mental retardation
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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.
|
Inpatients deemed eligible for the study, we be put on open-label risperidone
Other Names:
|
Healthy Volunteers
Healthy Volunteers will participate in MR imaging, Electroencephalogram , and cognitive testing.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
12 weeks
|
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.
|
12 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Anil Malhotra, MD, The Zucker Hillside Hospital
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Schizophrenia Spectrum and Other Psychotic Disorders
- Psychotic Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Agents
- Antidepressive Agents
- Dopamine Agonists
- Dopamine Agents
- Serotonin 5-HT1 Receptor Agonists
- Serotonin Receptor Agonists
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin Antagonists
- Dopamine D2 Receptor Antagonists
- Dopamine Antagonists
- Aripiprazole
- Risperidone
Other Study ID Numbers
- HS16-0411
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Psychotic Disorders
-
Medical College of WisconsinCompletedSchizophrenia | Affective Disorders | Psychotic Disorder | Psychotic Mood Disorder
-
Søren Dinesen ØstergaardCompletedAffective Disorders, PsychoticDenmark
-
Instituto de Investigación Hospital Universitario...CompletedSchizophrenia and Disorders With Psychotic Feature | Psychotic EpisodeSpain
-
Instituto de Investigación Hospital Universitario...Carlos III Health Institute; European Regional Development FundCompletedSchizophrenia and Disorders With Psychotic Features | Psychotic EpisodeSpain
-
Centre hospitalier de Ville-Evrard, FranceRecruiting
-
VA Office of Research and DevelopmentNot yet recruitingMI-CBTech: A Mobile Intervention for Community Integration in Homeless-Experienced Veterans With SMIHomelessness | Schizophrenia Spectrum Disorders | Psychotic Mood Disorders | Psychotic Affective Disorders | Ill-Housed PersonsUnited States
-
University of California, San DiegoActive, not recruitingSchizophrenia | Schizoaffective Disorder | Mood Disorder, PsychoticUnited States
-
University Hospital, CaenRecruiting
-
University of MinnesotaUniversity of California, San FranciscoCompletedPsychotic Disorders | Schizophrenia | Schizoaffective Disorder | Cognitive Impairment | Psychosis | Treatment | Psychotic Depression | Psychotic Episode | Active Control | Psychotic Mood DisordersUnited States
-
Boston Medical CenterNational Institute of Mental Health (NIMH); Beth Israel Deaconess Medical CenterCompletedPsychotic Disorders | Psychosis | Psychotic EpisodeUnited States
Clinical Trials on Risperidone or Aripiprazole (patients only)
-
Otsuka Pharmaceutical Development & Commercialization...Otsuka America PharmaceuticalCompletedSchizophrenia | Schizoaffective DisorderUnited States
-
ElsanCompletedNeuropathic PainFrance
-
Cliniques universitaires Saint-Luc- Université...CompletedSchizophreniaBelgium
-
University Hospital OstravaCompletedNasal Obstruction | Nasal Septum; Deviation | Nasal Mucosa HypertrophyCzechia
-
Centre Hospitalier Universitaire de NīmesCompletedRhinitis, Allergic | Asthma, AllergicFrance
-
Yale UniversityRecruiting
-
University of Sao Paulo General HospitalFundação de Amparo à Pesquisa do Estado de São Paulo; Conselho Nacional de...Completed
-
Kahramanmaras Sutcu Imam UniversityCompletedPeriodontitis | Inflammatory Response | Periodontal InflammationTurkey
-
University of FloridaNational Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health...Completed
-
Hospices Civils de LyonCompletedStroke | Transient Ischemic AttackFrance