Metabolic Signatures and Biomarkers in Schizophrenia

Duke University

Status and phase: Completed; Phase 1

Conditions: Schizophrenia

Treatments: Drug: Aripiprazole; Other: Healthy volunteers; Drug: Risperidone

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00466310

8370

Pro00008577

Details and patient eligibility

About

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.

Full 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.

Enrollment: 71 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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71 participants in 3 patient groups

Aripiprazole for 4 weeks

Active Comparator group

Description:

Blood is drawn for baseline. 20 Subjects are randomly assigned to receive Aripiprazole for weeks weeks with a starting dose of 10mg/day and the dose will be titrated to a maximum of 30mg /day based on effectiveness and tolerability. After 4 weeks of treatment, blood will be drawn again for metabolomics.

Treatment:

Drug: Aripiprazole

Risperidone for 4 weeks

Active Comparator group

Description:

Blood will be drawn for baseline evaluation. 20 Subjects will be randomly assigned to receive risperidone at a starting dose of 2mg/day, and can be increased to 6mg/day based on response of the subject. After 4 weeks of medication, blood is drawn again.

Treatment:

Drug: Risperidone

Healthy volunteers

Other group

Description:

Fasting blood samples will be drawn from healthy volunteers to match age, race and gender with the research subjects for comparison.

Treatment:

Other: Healthy volunteers