Metabolic Signatures and Biomarkers in Schizophrenia

NCT ID: NCT00466310

Last Updated: 2014-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2011-01-31

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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aripiprazole for 4 weeks

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.

Group Type: ACTIVE_COMPARATOR

Aripiprazole

Intervention Type: DRUG

Aripiprazole for 4 weeks

Risperidone for 4 weeks

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.

Group Type: ACTIVE_COMPARATOR

Risperidone

Intervention Type: DRUG

Subjects will be randomized to risperidone for 4 weeks

Healthy volunteers

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

Group Type: OTHER

Healthy volunteers

Intervention Type: OTHER

Healthy volunteers

Interventions

Aripiprazole

Aripiprazole for 4 weeks

Intervention Type: DRUG

Risperidone

Subjects will be randomized to risperidone for 4 weeks

Intervention Type: DRUG

Healthy volunteers

Healthy volunteers

Intervention Type: OTHER

Other Intervention Names

Abilify; Risperdal

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rima Kaddurah-Daouk, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

John Umstead Hospital

Butner, North Carolina, United States

Countries

United States

References

Storey JD, Tibshirani R. Statistical significance for genomewide studies. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5. doi: 10.1073/pnas.1530509100. Epub 2003 Jul 25.

Reference Type: BACKGROUND

PMID: 12883005 (View on PubMed)

Kaddurah-Daouk R, McEvoy J, Baillie R, Zhu H, K Yao J, Nimgaonkar VL, Buckley PF, Keshavan MS, Georgiades A, Nasrallah HA. Impaired plasmalogens in patients with schizophrenia. Psychiatry Res. 2012 Aug 15;198(3):347-52. doi: 10.1016/j.psychres.2012.02.019. Epub 2012 Apr 16.

Reference Type: RESULT

PMID: 22513041 (View on PubMed)

Other Identifiers

8370

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00008577

Identifier Type: -

Identifier Source: org_study_id