Metabolic Signatures and Biomarkers in Schizophrenia

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00466310
First received: April 25, 2007
Last updated: July 11, 2014
Last verified: March 2013

April 25, 2007
July 11, 2014
February 2007
January 2009   (final data collection date for primary outcome measure)
Total Plasmalogen Levels in the Lipid Profile [ Time Frame: Baseline ] [ Designated as safety issue: No ]
Plasmalogens are a subclass of glycerophospholipids and ubiquitous constituents of cellular membranes and serum lipoproteins. Several neurological disorders show decreased level of plasmalogens.
Quantitative mesaurements of over three hundred lipids within the eight lipid classes before and after treatment, using a lipodomics platform will highlight changes in the constituents of membrane phospholipids and in lipid storage and release pathways
Complete list of historical versions of study NCT00466310 on ClinicalTrials.gov Archive Site
Not Provided
Some changes in the lipid classes will be associated with therapeutic benefit and with development of metabolic side effects associated with drug use.
Not Provided
Not Provided
 
Metabolic Signatures and Biomarkers in Schizophrenia
Metabolic Signatures and Biomarkers in First Episode and Recurrent Patients With Schizophrenia in Comparison to Healthy Controls

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.

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.

Interventional
Phase 1
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Schizophrenia
  • Drug: Aripiprazole
    Aripiprazole for 4 weeks
    Other Name: Abilify
  • Drug: Risperidone
    Subjects will be randomized to risperidone for 4 weeks
    Other Name: Risperdal
  • Other: Healthy volunteers
    Healthy volunteers
  • Active Comparator: 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.
    Intervention: Drug: Aripiprazole
  • Active Comparator: 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.
    Intervention: Drug: Risperidone
  • Healthy volunteers
    Fasting blood samples will be drawn from healthy volunteers to match age, race and gender with the research subjects for comparison.
    Intervention: Other: Healthy volunteers

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
71
January 2011
January 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 60 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00466310
Pro00008577, 8370
No
Duke University
Duke University
Bristol-Myers Squibb
Principal Investigator: Rima Kaddurah-Daouk, MD Duke University
Duke University
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP