Schizophrenia
Conditions
Keywords
MRI, Imaging, Antipsychotic
Brief summary
This is a Phase 4, randomized, open-label, parallel group study designed to assess the clinical and biological effects of 12 months of treatment with long acting intramuscular (IM) aripiprazole (Abilify®) as measured by clinical and behavioral measures, and changes on magnetic resonance imaging (MRI) scans in subjects with schizophrenia compared with SOC oral antipsychotic medications and compared with a healthy control group.
Detailed description
This is a Phase 4, randomized, open-label, parallel group study designed to assess the clinical and biological effects of 12 months of treatment with long acting intramuscular (IM) aripiprazole (Abilify®) as measured by clinical and behavioral measures, and changes on magnetic resonance imaging (MRI) scans in subjects with schizophrenia compared with SOC oral antipsychotic medications and compared with a healthy control group. It is hypothesized that improved treatment compliance will lead to fewer white matter changes in the brain. Fewer white matter changes will be demonstrated via neuroimaging as increased FA and BPF values in the prefrontal region, and an increase in metabolites in a voxel centered on the anterior cingulate cortex (ACC) as seen with MRS. Therefore, the aim of this study is to examine the structural and metabolic effects of aripiprazole (Abilify®) once monthly in patients with schizophrenia using MRI techniques and to examine these effects in association with cognitive and clinical measures.
Interventions
A total of 15 to 20 subjects with schizophrenia will receive SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI(Geodon®)) or once monthly aripiprazole (Abilify®), PO daily, in accordance with their respective product labeling.
DRUGIM aripiprazole once monthly
A total of 30 to 40 subjects with schizophrenia will receive aripiprazole (Abilify®) monthly, at a starting dose of 400 mg IM or an approved dose based on the investigator's judgment and in accordance with product labeling.
OTHERNo Treatment
A total of 15 healthy controls will participate in the study and will not receive medication
Sponsors
Otsuka America Pharmaceutical
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
for All Subjects * Are able to provide written informed consent. * Are male and female subjects 18 to 35 years of age, inclusive, at time of informed consent. Inclusion Criteria for Subjects with Schizophrenia * Have a current diagnosis of schizophrenia as defined by DSM IV-TR criteria and a history of the illness for at least 1 year prior to screening and at least two prior psychotic episodes based on medical records or a qualified and reliable health care provider. * Require, in the investigator's judgment, chronic treatment with an antipsychotic medication. * Are able to understand the nature of the study and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, IM depot injection, and discontinuation of prohibited concomitant medications, read and understand the written word in order to complete subject-reported outcomes measures, and be reliably rated on assessment scales. * Are male and female subjects who are surgically sterile (i.e., have undergone orchiectomy or hysterectomy, respectively; female subjects who have been postmenopausal for at least 12 consecutive months; or male and female subjects who agree to remain abstinent or to practice double barrier forms of birth control from trial screening through 30 days (for females) and 90 days (for males) from the last dose of IMP for SOC oral antipsychotics and 150 days for females and 180 days for males for aripiprazole depot. If employing birth control, two of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device, birth control pill, birth control implant, birth control depot injections, condom, or sponge with spermicide.
Exclusion criteria
All Subjects * Presence of any metal implants, pacemakers, unremovable prosthetic device, or other device or situation that may preclude imaging * History of a head injury with loss of consciousness \> 5 minutes * Has a significant medical condition that would expose the subject to undue risk or interfere with study assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Changes in Fractional Anisotropy (FA) | 12 months | To determine if there are differences in prefrontal white matter fractional anisotropy (FA) in subjects with schizophrenia from baseline at 12 months of treatment with aripiprazole (Abilify®) once monthly compared with standard of care (SOC) oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI (Geodon®)). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Control No Treatment: A total of 15 healthy controls will participate in the study and will not receive medication | 16 |
| Individuals With Schizophrenia (Group A) Standard of Care Oral antipsychotics: A total of 15 to 20 subjects with schizophrenia will receive SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI(Geodon®)) or once monthly aripiprazole (Abilify®), PO daily, in accordance with their respective product labeling. | 15 |
| Individuals With Schizophrenia (Group B) IM aripiprazole once monthly: A total of 30 to 40 subjects with schizophrenia will receive aripiprazole (Abilify®) monthly, at a starting dose of 400 mg IM or an approved dose based on the investigator's judgment and in accordance with product labeling. | 16 |
| Total | 47 |
Baseline characteristics
| Characteristic | Healthy Control | Individuals With Schizophrenia (Group A) | Individuals With Schizophrenia (Group B) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 15 Participants | 16 Participants | 47 Participants |
| Age, Continuous | 28 years | 30 years | 28 years | 28 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 7 Participants | 5 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 8 Participants | 10 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 16 participants | 15 participants | 16 participants | 47 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 3 Participants | 14 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 13 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 1 / 9 | 1 / 10 |
| other Total, other adverse events | 0 / 16 | 0 / 9 | 0 / 10 |
| serious Total, serious adverse events | 0 / 16 | 0 / 9 | 0 / 10 |
Outcome results
Primary
Number of Participants With Changes in Fractional Anisotropy (FA)
To determine if there are differences in prefrontal white matter fractional anisotropy (FA) in subjects with schizophrenia from baseline at 12 months of treatment with aripiprazole (Abilify®) once monthly compared with standard of care (SOC) oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI (Geodon®)).
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Healthy Control | Number of Participants With Changes in Fractional Anisotropy (FA) | 13 Participants |
| Individuals With Schizophrenia (Group A) | Number of Participants With Changes in Fractional Anisotropy (FA) | 9 Participants |
| Individuals With Schizophrenia (Group B) | Number of Participants With Changes in Fractional Anisotropy (FA) | 7 Participants |