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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
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Aripiprazole
Drug: Risperidone
Other: Healthy volunteers
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Metabolic Signatures and Biomarkers in First Episode and Recurrent Patients With Schizophrenia in Comparison to Healthy Controls

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 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.


Enrollment: 71
Study Start Date: February 2007
Study Completion Date: January 2011
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Aripiprazole
Aripiprazole for 4 weeks
Other Name: Abilify
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.
Drug: Risperidone
Subjects will be randomized to risperidone for 4 weeks
Other Name: Risperdal
Healthy volunteers
Fasting blood samples will be drawn from healthy volunteers to match age, race and gender with the research subjects for comparison.
Other: Healthy volunteers
Healthy volunteers

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00466310

Locations
United States, North Carolina
John Umstead Hospital
Butner, North Carolina, United States, 27509
Sponsors and Collaborators
Duke University
Bristol-Myers Squibb
Investigators
Principal Investigator: Rima Kaddurah-Daouk, MD Duke University
  More Information

Publications:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00466310     History of Changes
Other Study ID Numbers: Pro00008577, 8370
Study First Received: April 25, 2007
Results First Received: April 5, 2011
Last Updated: July 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Schizophrenia
Metabolomics

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Aripiprazole
Risperidone
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 25, 2014