Schizophrenia
Conditions
Keywords
Schizophrenia, Metabolomics
Brief summary
We plan to use a metabolomics lipid platform to map biochemical signatures in unmedicated schizophrenic patients prior to and 4 weeks post treatment with the antipsychotic drug aripiprazole and compare that to lipid perturbations induced by risperidone. These drugs have inherently different risk for metabolic adverse effects and patients respond to them differently. Metabolic signatures for the drugs capture significant biochemical information that could explain part of the basis for varied drug response within individuals and will highlight pathways implicated in drug action and in disease pathogenesis possibly enabling new drug design strategies. In addition, we will compare patients to healthy controls at baseline in regard lipid profiles.
Detailed description
Schizophrenia (SCH) is a devastating mental disease that affects the human population worldwide with an incidence of about 1%. Most individuals with this illness benefit from long-term pharmacotherapy, however, the therapeutic effects of antipsychotic treatment are inconsistent, incomplete, and often countered by significant side-effects associated with long-term physical morbidity (e.g., tardive dyskinesia, obesity, hyperglycemia, hyperlipidemia. Metabolomics is a powerful new technology that provides a snap shot of biochemical pathways at a particular point in time. It has been earmarked as an important area to develop under the NIH roadmap initiative. We plan to use this platform to map biochemical signatures in unmedicated schizophrenic patients prior to and 4 weeks post treatment with the antipsychotic drug aripiprazole and compare that to lipid perturbations induced by risperidone. These drugs have inherently different risk for metabolic adverse effects and patients respond to them differently. Metabolic signatures for the drugs capture significant biochemical information that could explain part of the basis for varied drug response within individuals and will highlight pathways implicated in drug action and in disease pathogenesis possibly enabling new drug design strategies.In addition, we will compare patients to healthy controls at baseline in regard lipid profiles, to assess whether lipid profiles differ between unmedicated schizophrenia patients and healthy controls.
Interventions
DRUGAripiprazole
Aripiprazole for 4 weeks
DRUGRisperidone
Subjects will be randomized to risperidone for 4 weeks
OTHERHealthy volunteers
Healthy volunteers
Sponsors
Bristol-Myers Squibb
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18-60 years * Diagnosis of schizophrenia * Actively psychotic * No more than a single dose of antipsychotic in the preceding 2 weeks
Exclusion criteria
* Mental retardation, epilepsy or history of head trauma * Substance use disorder that explains the majority of the psychopathology * Pregnant or lactating females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Plasmalogen Levels in the Lipid Profile | Baseline | Plasmalogens are a subclass of glycerophospholipids and ubiquitous constituents of cellular membranes and serum lipoproteins. Several neurological disorders show decreased level of plasmalogens. |
Countries
United States
Participant flow
Recruitment details
Unmedicated patients treated for a first psychotic episode (n = 20), and patients treated for psychotic relapse of schizophrenia or schizoaffective disorder(n = 20). Controls who had no personal history of psychotic illness or relatives with psychotic illnesses,(n = 31). Individuals receiving treatment for diabetes or hyperlipidemia were excluded.
Participants by arm
| Arm | Count |
|---|---|
| First Episode Schizophrenics These are subjects with no prior schizophrenic episodes | 20 |
| Recurrent Episode Schizophrenics These subjects have had at least one prior schizophrenic episode. | 20 |
| Healthy Volunteers Fasting blood samples were drawn at baseline from 31 healthy matched controls. | 31 |
| Total | 71 |
Baseline characteristics
| Characteristic | Recurrent Episode Schizophrenics | Healthy Volunteers | First Episode Schizophrenics | 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 | 20 Participants | 31 Participants | 20 Participants | 71 Participants |
| Age, Continuous | 36.6 years STANDARD_DEVIATION 12.7 | 37.9 years STANDARD_DEVIATION 9.1 | 27 years STANDARD_DEVIATION 9.8 | 33.63 years STANDARD_DEVIATION 11.6 |
| Region of Enrollment United States | 20 participants | 31 participants | 20 participants | 71 participants |
| Sex: Female, Male Female | 5 Participants | 25 Participants | 7 Participants | 37 Participants |
| Sex: Female, Male Male | 15 Participants | 6 Participants | 13 Participants | 34 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 | 0 / 20 | 0 / 20 | 0 / 31 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 31 |
Outcome results
Primary
Total Plasmalogen Levels in the Lipid Profile
Plasmalogens are a subclass of glycerophospholipids and ubiquitous constituents of cellular membranes and serum lipoproteins. Several neurological disorders show decreased level of plasmalogens.
Time frame: Baseline
Population: 17 of the 31 available controls were age and BMI matched to the schizophrenia subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| First Episode Schizophrenics | Total Plasmalogen Levels in the Lipid Profile | 57.65 nmoles/gram | Standard Deviation 14.37 |
| Recurrent Episode Schizophrenics | Total Plasmalogen Levels in the Lipid Profile | 59.57 nmoles/gram | Standard Deviation 15.87 |
| Healthy Volunteers | Total Plasmalogen Levels in the Lipid Profile | 75 nmoles/gram | Standard Deviation 19.17 |
Comparison: A wilcoxon rank sum test was performed comparing baseline plasmalogen values, comparing schizophrenia subjects vs controls.P values from this analysis were adjusted for false discovery rates by the method of Storey and Tribshiani.p-value: 0.0149Wilcoxon (Mann-Whitney)