Psychotic DisordersNCT02822092
Striatal Connectivity and Clinical Outcome in Psychosis
An observational study of Psychotic Disorders, run by Northwell Health at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Psychotic Disorders
- What is being tested?
- Risperidone or Aripiprazole (patients only)
- How many people
- 196 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2016to Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 40 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Healthy Volunteers and Patients with Psychotic Disorders
Who may be able to join
- 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
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- for women, negative pregnancy test and agreement to use a medically accepted birth control method.
- age 15 to 40
- competent to sign informed consent
Who cannot join
- 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
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- Healthy Volunteers
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Psychotic Disorders
- Being tested
- Risperidone or Aripiprazole (patients only)
- Medical subject headings
- Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Risperidone or Aripiprazole (patients only)Drug
Also called Risperidal, Aripiprazole
Inpatients deemed eligible for the study, we be put on open-label risperidone
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Risperidone or Aripiprazole (patients only) | |
| Healthy Volunteers | Healthy Volunteers will participate in MR imaging, Electroencephalogram , and cognitive testing. |
What is being measured
The primary outcome is the main question the study is designed to answer.
efficacy of risperidone or aripiprazole for psychotic symptoms
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
Measured: 12 weeks
Secondary outcomes (2)
Relationship between efficacious treatment of psychotic symptoms and changes in functional connectivity of the striatum
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
Measured: 12 weeks
Predicting treatment efficacy from baseline fMRI scans
To examine whether baseline fMRI scans can predict treatment efficacy which will be measured by the Brief Psychiatric Rating Scale.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2016 (estimated)
- Study startJul 2016
- Primary completionDec 2023
- Study completionDec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Psychotic DisordersStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 196 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Anil Malhotra, MD, Principal investigator, The Zucker Hillside Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02822092
- Sponsor's protocol ID
- HS16-0411
- Status last verified
- Feb 2024
- First submitted
- 27 Jun 2016
- Last updated
- 21 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Striatal Connectivity and Clinical Outcome in Psychosis
- ClinicalTrials.gov ID
- NCT02822092
- Acronym / sponsor ID
- HS16-0411
- Conditions
- Psychotic Disorders
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 196 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Jul 2016
- Primary completion
- Dec 2023 (actual)
- Study completion
- Dec 2023 (actual)
- First posted
- 4 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with Psychotic Disorders taking Risp. or Arip. | – | Drug: Risperidone or Aripiprazole (patients only)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. |
| Healthy Volunteers | – | –Healthy Volunteers will participate in MR imaging, Electroencephalogram , and cognitive testing. |
Who may qualify
- Ages
- 15 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Healthy Volunteers and Patients with Psychotic Disorders
Key inclusion criteria (9 listed)
- 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;
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Risperidone or Aripiprazole (patients only)Also: Risperidal, AripiprazoleInpatients deemed eligible for the study, we be put on open-label risperidone | Drug | Patients with Psychotic Disorders taking Risp. or Arip. |
Primary outcome
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
2 secondary outcomes
Relationship between efficacious treatment of psychotic symptoms and changes in functional connectivity of the striatum
Time frame: 12 weeks
Predicting treatment efficacy from baseline fMRI scans
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anil Malhotra, MD principal investigator
The Zucker Hillside Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Psychotic Disorders, run by Northwell Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
efficacy of risperidone or aripiprazole for psychotic symptoms (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2024.