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| ID | Type | Description | Link |
|---|---|---|---|
| 8370 | Other Identifier | Duke legacy protocol number |
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| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aripiprazole for 4 weeks | Active Comparator | 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. |
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| Risperidone for 4 weeks | Active Comparator | 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. |
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| Healthy volunteers | Other | Fasting blood samples will be drawn from healthy volunteers to match age, race and gender with the research subjects for comparison. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aripiprazole | Drug | Aripiprazole for 4 weeks |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rima Kaddurah-Daouk, MD | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| John Umstead Hospital | Butner | North Carolina | 27509 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12883005 | Background | 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. | |
| 22513041 | Result | 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. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | First Episode Schizophrenics | Schizophrenia subjects with no prior episodes |
| FG001 | Recurrent Episode Schizophrenics | Schizophrenia subjects with at least one prior episode |
| FG002 | Healthy Volunteers | Fasting blood samples were drawn at baseline from 31 healthy matched controls. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | First Episode Schizophrenics | These are subjects with no prior schizophrenic episodes |
| BG001 | Recurrent Episode Schizophrenics | These subjects have had at least one prior schizophrenic episode. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 17 of the 31 available controls were age and BMI matched to the schizophrenia subjects. | Posted | Mean | Standard Deviation | nmoles/gram | Baseline |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | First Episode Schizophrenics | These are subjects with no prior schizophrenic episodes |
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Limited to patients admitted to Psychiatric facility
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rima Kaddurah-Douk, Associate Professor | DUMC | 919-684-2611 | rima.kaddurah-daouk@duke.edu |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000068180 | Aripiprazole |
| D018967 | Risperidone |
| ID | Term |
|---|---|
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D015363 | Quinolones |
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| Risperidone | Drug | Subjects will be randomized to risperidone for 4 weeks |
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| Healthy volunteers | Other | Healthy volunteers |
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| BG002 | Healthy Volunteers | Fasting blood samples were drawn at baseline from 31 healthy matched controls. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| OG002 | Healthy Volunteers | Fasting blood samples were drawn at baseline from 31 healthy matched controls. |
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| 0 |
| 20 |
| 0 |
| 20 |
| EG001 | Recurrent Episode Schizophrenics | These subjects have had at least one prior schizophrenic episode. | 0 | 20 | 0 | 20 |
| EG002 | Healthy Volunteers | Fasting blood samples were drawn at baseline from 31 healthy matched controls. | 0 | 31 | 0 | 31 |
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| D011804 |
| Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |