Schizophrenia
Conditions
Keywords
First episode or recent onset
Brief summary
The goal of this project is to show that the best possible option for preventing relapses in patients suffering from first episode (\<1 year of anti-psychotic medication) or early phase (\< 5 years of lifetime exposure to anti-psychotic medication) schizophrenia is by enhancing medication adherence. The study is designed to answer the question of whether the use of long-acting injectable (LAI) antipsychotics early in the course of treatment can break the cycle of frequent relapse that affects so many patients with early phase schizophrenia. The participating research sites (not individual patients) will be randomly assigned to either medication prescribed by their treating physician (with no restrictions) or to a regimen that involves a monthly long acting injectable antipsychotic. The sites will be assigned on a one to one basis to either of the arms taking into account types of patient population and geographical area. Patients enrolled in the study will participate in regular assessments either over the phone or in person and be followed for a period of 2 years. The primary outcome measure is time to first hospitalization.
Detailed description
Approximately 40 U.S. sites will participate in the study in order to enroll approximately 500 patients over a year period. They will be recruited into two cohorts - the first episode cohort and the early phase (EP) cohort, with approximately 250 patients in each cohort. Enrollment of patients will be discontinued when the appropriate number for the target for each cohort is reached. After providing written informed consent, patients will be screened for general eligibility by the clinical team at the site. Basic demographic data will be collected to determine suitability for inclusion into the study. The site will complete an information interview comprising data regarding symptomology and history, but the diagnosis of schizophrenia will fall to a centralized, remote blinded rater to enable consistency for eligibility. Prescribers at sites in the clinician's choice arm can treat the patients in the manner most appropriate for that individual. Prescribers at sites in the Aripiprazole Once Monthly arm monthly will prescribe and administer the medication according to recommendations contained in the product labeling. For a period of 2 years all subjects will receive bimonthly calls inquiring about visits to emergency rooms and hospitalization. At 4 month intervals information on use of services, insurance status, work, school attendance, and other service use outcomes will be assessed.
Interventions
DRUGAny FDA approved antipsychotic agent
Investigators are free to choose the most appropriate treatment for their clients
DRUGaripiprazole long acting injectable formulation
Sponsors
Otsuka America Pharmaceutical
Vanguard Research Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
Are able to provide written informed consent Have a confirmed diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual (DSM) 5 criteria using the SCID (Structured Clinical Interview for DSM disorders) Are between the ages of 18 and 35, inclusive Have the following history with antipsychotic medications 1. First episode subjects: \< 1 year of lifetime exposure to antipsychotic medication and only one episode of psychosis 2. EP subjects: between 1 year and 5 years of lifetime exposure to antipsychotic medication or subjects with \< 1 year of lifetime antipsychotic medication and more than one episode of psychosis. For LAI subjects: Must be willing to accept an injectable form of treatment
Exclusion criteria
Have a current primary DSM-5 diagnosis other than schizophrenia, including schizophreniform disorder, schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, and amnestic or other cognitive disorders. For LAI sites only - have a known allergy or intolerance to aripiprazole, or a past negative response to aripiprazole that is not explained by nonadherence Be pregnant or lactating Have any unstable medical condition that, in the opinion of the investigator, would be detrimental to the subject or would confound the results of the study Subjects in the MRI subset only- presence of any metal implants, pacemakers, irremovable prosthetic devices, or other devices or situations that may preclude imaging
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Hospitalization | Hospitalizations assessed every 2 months from baseline to Month 24 | Assessments are done using best available data and patient interviews |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Psychiatric Hospitalizations Per Treatment Arm | Measured every 2 months from baseline to month 24 | Assessments are completed using best available data and patient interviews |
| Brief Psychotic Rating Scale (BPRS) Total Score | Measured at Month 12 and Month 24 | The Brief Psychotic Rating Scale is an 18 item scale where each item is rated 1-7, the minimum total score is 18 and the maximum total score is 126. Higher scores indicate more severe symptoms. |
| Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Sum of Scores | Measured at Month 12 and Month 24 | Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a 12 item scale with a total score range of 0 to 321 with higher scores indicating better cognitive functioning |
| Quality of Life (QLS) Total Score | Measured at Month 12 and Month 24 | Quality of Life (QLS) is a 21 item scale where each item is rated from 0 to 7, the minimum score is 0 and the maximum score is 126 with higher scores indicating better overall functioning. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clinician's Choice Prescribers are not limited in the choice of treatment they can administer to their clients to alleviate the symptoms of schizophrenia. Any FDA approved antipsychotic agent can be used. Clients in the study wil be followed for 2 years
Any FDA approved antipsychotic agent: Investigators are free to choose the most appropriate treatment for their clients | 255 |
| Aripiprazole Once Monthly Aripiprazole long acting injectable formulation, 400mg per dose is to be administered once monthly. Clients in the study will be followed for 2 years
aripiprazole long acting injectable formulation | 234 |
| Total | 489 |
Baseline characteristics
| Characteristic | Clinician's Choice | Total | Aripiprazole Once Monthly |
|---|---|---|---|
| Age, Continuous | 24.7 years STANDARD_DEVIATION 4.1 | 25.2 years STANDARD_DEVIATION 4.2 | 25.7 years STANDARD_DEVIATION 4.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 18 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 104 Participants | 213 Participants | 109 Participants |
| Race (NIH/OMB) More than one race | 45 Participants | 84 Participants | 39 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 91 Participants | 171 Participants | 80 Participants |
| Region of Enrollment United States | 255 participants | 489 participants | 234 participants |
| Sex: Female, Male Female | 59 Participants | 121 Participants | 62 Participants |
| Sex: Female, Male Male | 196 Participants | 368 Participants | 172 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 255 | 0 / 234 |
| other Total, other adverse events | 161 / 241 | 169 / 222 |
| serious Total, serious adverse events | 104 / 255 | 68 / 234 |
Outcome results
Primary
Time to First Hospitalization
Assessments are done using best available data and patient interviews
Time frame: Hospitalizations assessed every 2 months from baseline to Month 24
Population: Intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clinician's Choice | Time to First Hospitalization | 530.6 days |
| Aripiprazole Once Monthly | Time to First Hospitalization | 613.7 days |
Secondary
Brief Psychotic Rating Scale (BPRS) Total Score
The Brief Psychotic Rating Scale is an 18 item scale where each item is rated 1-7, the minimum total score is 18 and the maximum total score is 126. Higher scores indicate more severe symptoms.
Time frame: Measured at Month 12 and Month 24
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clinician's Choice | Brief Psychotic Rating Scale (BPRS) Total Score | Baseline | 35.59 Scores on a scale | Standard Deviation 9.4 |
| Clinician's Choice | Brief Psychotic Rating Scale (BPRS) Total Score | Month 12 | 30.7 Scores on a scale | Standard Deviation 8.73 |
| Clinician's Choice | Brief Psychotic Rating Scale (BPRS) Total Score | Month 24 | 30.73 Scores on a scale | Standard Deviation 8.86 |
| Aripiprazole Once Monthly | Brief Psychotic Rating Scale (BPRS) Total Score | Baseline | 35.45 Scores on a scale | Standard Deviation 9.27 |
| Aripiprazole Once Monthly | Brief Psychotic Rating Scale (BPRS) Total Score | Month 12 | 31.31 Scores on a scale | Standard Deviation 9.32 |
| Aripiprazole Once Monthly | Brief Psychotic Rating Scale (BPRS) Total Score | Month 24 | 30.87 Scores on a scale | Standard Deviation 9.13 |
Secondary
Quality of Life (QLS) Total Score
Quality of Life (QLS) is a 21 item scale where each item is rated from 0 to 7, the minimum score is 0 and the maximum score is 126 with higher scores indicating better overall functioning.
Time frame: Measured at Month 12 and Month 24
Population: Intent to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clinician's Choice | Quality of Life (QLS) Total Score | Baseline | 63.60 Scores on a scale | Standard Deviation 19.36 |
| Clinician's Choice | Quality of Life (QLS) Total Score | Month 12 | 68.45 Scores on a scale | Standard Deviation 23.13 |
| Clinician's Choice | Quality of Life (QLS) Total Score | Month 24 | 62.21 Scores on a scale | Standard Deviation 24.54 |
| Aripiprazole Once Monthly | Quality of Life (QLS) Total Score | Baseline | 58.40 Scores on a scale | Standard Deviation 19.83 |
| Aripiprazole Once Monthly | Quality of Life (QLS) Total Score | Month 12 | 65.02 Scores on a scale | Standard Deviation 21.6 |
| Aripiprazole Once Monthly | Quality of Life (QLS) Total Score | Month 24 | 70.05 Scores on a scale | Standard Deviation 24.28 |
Secondary
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Sum of Scores
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a 12 item scale with a total score range of 0 to 321 with higher scores indicating better cognitive functioning
Time frame: Measured at Month 12 and Month 24
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clinician's Choice | Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Sum of Scores | Baseline | 182.4 Scores on a scale | Standard Deviation 33.1 |
| Clinician's Choice | Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Sum of Scores | Month 12 | 189.2 Scores on a scale | Standard Deviation 34.9 |
| Clinician's Choice | Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Sum of Scores | Month 24 | 194.1 Scores on a scale | Standard Deviation 33.2 |
| Aripiprazole Once Monthly | Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Sum of Scores | Baseline | 177.7 Scores on a scale | Standard Deviation 35.4 |
| Aripiprazole Once Monthly | Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Sum of Scores | Month 12 | 178.2 Scores on a scale | Standard Deviation 34.9 |
| Aripiprazole Once Monthly | Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Sum of Scores | Month 24 | 180.8 Scores on a scale | Standard Deviation 33.6 |
Secondary
Total Number of Psychiatric Hospitalizations Per Treatment Arm
Assessments are completed using best available data and patient interviews
Time frame: Measured every 2 months from baseline to month 24
Population: Intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clinician's Choice | Total Number of Psychiatric Hospitalizations Per Treatment Arm | 208 Hospitalizations |
| Aripiprazole Once Monthly | Total Number of Psychiatric Hospitalizations Per Treatment Arm | 133 Hospitalizations |