Study of the Impact of Aripiprazole (Abilify®) Once Monthly Versus Standard of Care Oral Antipsychotic Medications on Changes in Brain Structure and Metabolism
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Standard of Care Oral antipsychotics; IM aripiprazole once monthly; No Treatment
Intervention description: 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.; 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.; A total of 15 healthy controls will participate in the study and will not receive medication
Intervention MeSH terms: Aripiprazole; Antipsychotic Agents
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Maximum age: 35 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: MRI; Imaging; Antipsychotic

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.

      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.
    

Eligibility criteria:

        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.

        Exclusion Criteria for Subjects with Schizophrenia

          -  Has a current DSM-IV-TR diagnosis other than schizophrenia, including schizophreniform
             disorder, schizoaffective disorder, major depressive disorder, bipolar disorder,
             delirium, dementia, amnestic or other cognitive disorders. Also excluded are subjects
             with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial
             personality disorder.

          -  Is considered resistant/refractory to antipsychotic treatment by history (failed two
             prior antipsychotic medication trials) or response only to clozapine.

          -  Has a significant risk of violent behavior or a significant risk of committing suicide
             based on history or investigator's discretion.

          -  Has met DSM-IV-TR criteria for any significant substance use disorder within 3 months
             prior to screening, excluding caffeine, nicotine, or marijuana.

          -  Is known to be allergic, intolerant, or unresponsive to prior treatment with
             aripiprazole or other quinolinones, or hypersensitivity to antipsychotic agents,
             including aripiprazole.

          -  Has a history of neuroleptic malignant syndrome or clinically significant tardive
             dyskinesia at screening per the investigator's discretion.

          -  Has a history of seizures or any other medical condition that would expose the subject
             to undue risk or interfere with study assessments.

          -  Is involuntarily incarcerated.

          -  Has undergone electroconvulsive therapy in the 2 years prior to enrollment in the
             study.

          -  Has used an investigational agent or has participated in a clinical study with
             aripiprazole IM depot or any other antipsychotic depot preparation within 30 days of
             screening.

          -  Has clinically significant abnormalities in laboratory test results, vital signs, or
             ECG results.

          -  Requires more than one benzodiazepine beyond screening (e.g., lorazepam and oxazepam).

          -  Fails to washout from prohibited concomitant medications, including the use of or
             CYP3A4 inducers, a second antipsychotic, antidepressants (including monoamine oxidase
             inhibitors), and mood stabilizers.