Schizophrenia
Conditions
Keywords
Schizoaffective Disorder
Brief summary
This study will compare the safety and effectiveness of three different antipsychotic medications, as well as the use of other medications to limit treatment side effects, in adults with schizophrenia.
Detailed description
Schizophrenia is a chronic brain disease affecting approximately 1% of Americans. Antipsychotic medications can treat some of the most severe symptoms of schizophrenia, but they are not a cure, are often taken for long periods of time, and can have severe side effects. Other, secondary medications can provide relief from some of the most common severe side effects. This study will compare the safety and effectiveness of three different antipsychotic medications, as well as the use of additional medications to limit treatment side effects, in adults with schizophrenia. Participation in this study will last 28 to 30 weeks and include 11 visits to a study clinic. Each visit will last 2 to 3 hours. The first 2 visits will include screening and baseline measurements. The screening visit will take place at study entry, and the baseline visit will take place 3 to 14 days later. Study visits will then occur 1, 2, and 4 weeks after the baseline visit, followed by monthly visits. At the baseline visit participants will be randomly assigned to receive olanzapine, perphenazine, or aripiprazole for 28 weeks. Dosage for all three antipsychotic medications will start at low levels and be increased to full strength over 2 weeks. If participants are taking another antipsychotic when they enter the study, this 2-week period will also be used to slowly reduce and then end treatment with the non-study antipsychotic. Side effects to all three antipsychotics will be monitored, and, depending on the side effect, one of three different medications will be added to the treatment regimen. If increased cholesterol levels are experienced with any antipsychotic, simvastatin will be added; if weight gain is experienced, metformin will be added; if involuntary movements, inner restlessness, or muscle stiffness are experienced, benztropine will be added. Because of already known side effects, participants assigned to olanzapine or perphenazine will automatically add metformin or benztropine, respectively, to their regimens. Starting on the third study visit, participants will also undergo a behavioral treatment aimed at reducing cardiovascular risk factors. This behavioral treatment will involve nine 20-minute sessions, with phone calls being made to participants between sessions. During each study visit, assessments will be made of schizophrenia symptoms, side effects, adherence to medication regimen, vital signs, waist circumference, and weight. Participants will also complete a questionnaire on use of health care services and undergo instructions on exercise and eating right. On visits 1, 5, 7, and 11, blood will be drawn for standard lab tests. Additional measures at the screening visit will include questions about medical and psychiatric history, a urine test for drugs, and a questionnaire about physical and social activities.
Interventions
DRUGOlanzapine
Daily tablets of 10 to 30 mg
DRUGPerphenazine
Daily tablets of 8 to 24 mg
DRUGAripiprazole
Daily tablets of 10 to 30 mg
DRUGMetformin
Daily tablets of 850 to 2550 mg
DRUGSimvastatin
Daily tablets of 20 to 40 mg
DRUGBenztropine
Daily tablets of 1 to 2 mg
Sponsors
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of schizophrenia or schizoaffective disorder, as defined by DSM-IV-TR criteria and confirmed by the Structured Clinical Interview for DSM-IV (SCID) * Treated with antipsychotic medication for less than 5 years * Adequate decisional capacity to make a choice about participating in this research study. Adequate decisional capacity will be determined through the aid of a 10-item decisional capacity quiz adapted from the University of California, San Diego, Brief Assessment of Capacity to Consent (UBACC) scale. * Psychotic exacerbation within the month prior to study entry that required psychiatric hospitalization or an increased level of care * Willing to use an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study. Acceptable methods include oral, injectable, or implanted contraceptives; intrauterine devices; or barrier methods, such as condoms, diaphragm, and spermicides.
Exclusion criteria
* Body mass index at or above 35 kg/m2 or below 18 kg/m2 * Hemoglobin A1c level at or above 7% * Hematocrit level at or above 31% * Non-high density lipoprotein cholesterol at or above 190 mg/dL * Triglycerides at or above 500 mg/dL * Documented failure, defined as inefficacy or intolerability, with an adequate trial of olanzapine, perphenazine, or aripiprazole. Adequate trials last at least 4 weeks at a minimum dose of 15 mg/day of aripiprazole, 15 mg/day of olanzapine, or 16 mg/day of perphenazine. * Current treatment with olanzapine, perphenazine, or aripiprazole for more than 1 month * Known hypersensitivity to metformin, simvastatin, or benztropine * Treatment with a medication prescribed for weight loss * Diagnosis of diabetes mellitus or treatment with insulin or other diabetes medication * Contraindications to metformin use, including any of the following: * Diagnosis of congestive heart failure * Renal impairment, defined as serum creatinine at or above 1.5 in males and 1.4 in females, or creatinine estimated glomerular filtration rate (GFR) outside of normal limits * Hepatic disease, defined as aspartate transaminase (AST), alanine transaminase (ALT), or c-glutamyl transferase (CGT) more than 1.5 times upper limit of normal (ULN) or total bilirubin more than 1.2 times ULN * Metabolic acidosis, defined as a serum CO2 level less than the lower limit of normal * Recent (in the past 30 days) or scheduled radiological studies involving iodinated contrast material * Alcohol abuse or dependence, as determined by SCID within the past month * Concurrent treatment with certain drugs known to increase metformin blood levels * Any unstable or serious medical condition, as judged by the investigator * Pregnant or breastfeeding * Diagnosis of mental retardation or delirium, as defined by the DSM-IV-TR
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of Randomizing a Cohort of Participants Meeting the Inclusion and Exclusion Criteria of the Study | Baseline | Goal was to randomize 60 participants who met eligibility criteria. |
Secondary
| Measure | Time frame |
|---|---|
| Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Measured over 28 weeks of study visits |
Countries
United States
Participant flow
Recruitment details
This feasibility-focused pilot study was conducted at 14 clinical sites affiliated with the Schizophrenia Trials Network in 2008-9.
Participants by arm
| Arm | Count |
|---|---|
| Olanzapine Participants will receive treatment with olanzapine and metformin, with the possible addition of simvastatin or benztropine, depending on side effects. | 6 |
| Perphenazine Participants will receive treatment with perphenazine and benztropine, with the possible addition of simvastatin or metformin, depending on side effects. | 9 |
| Aripiprazole Participants will receive treatment with aripiprazole, with the possible addition of simvastatin, metformin, or benztropine, depending on side effects. | 6 |
| Total | 21 |
Baseline characteristics
| Characteristic | Total | Olanzapine | Perphenazine | Aripiprazole |
|---|---|---|---|---|
| Age Continuous | 29 years STANDARD_DEVIATION 8.2 | 30 years STANDARD_DEVIATION 9.7 | 30 years STANDARD_DEVIATION 8.1 | 27 years STANDARD_DEVIATION 7.9 |
| Sex: Female, Male Female | 8 Participants | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 13 Participants | 4 Participants | 5 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 9 / 9 | 6 / 6 |
| serious Total, serious adverse events | 2 / 6 | 3 / 9 | 3 / 6 |
Outcome results
Primary
Feasibility of Randomizing a Cohort of Participants Meeting the Inclusion and Exclusion Criteria of the Study
Goal was to randomize 60 participants who met eligibility criteria.
Time frame: Baseline
Population: Total study population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Study | Feasibility of Randomizing a Cohort of Participants Meeting the Inclusion and Exclusion Criteria of the Study | 21 participants |
Secondary
Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment
Time frame: Measured over 28 weeks of study visits
Population: Analysis population is those randomized. Outcome is discontinuation from study treatment before 28 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Inefficacy | 0 participants |
| Overall Study | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Unacceptable side effects | 0 participants |
| Overall Study | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Patient refusal | 3 participants |
| Overall Study | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Drop-out, no information available | 2 participants |
| Overall Study | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Administrative | 1 participants |
| Overall Study | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Completed trial without discontinuing | 0 participants |
| Perphenazine | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Completed trial without discontinuing | 2 participants |
| Perphenazine | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Inefficacy | 1 participants |
| Perphenazine | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Drop-out, no information available | 1 participants |
| Perphenazine | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Administrative | 5 participants |
| Perphenazine | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Unacceptable side effects | 0 participants |
| Perphenazine | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Patient refusal | 0 participants |
| Aripiprazole | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Unacceptable side effects | 0 participants |
| Aripiprazole | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Patient refusal | 0 participants |
| Aripiprazole | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Completed trial without discontinuing | 2 participants |
| Aripiprazole | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Drop-out, no information available | 0 participants |
| Aripiprazole | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Inefficacy | 1 participants |
| Aripiprazole | Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment | Administrative | 3 participants |