Personalized Warfarin Dosing by Genomics and Computational Intelligence
Personalized Warfarin Dosing Using Genomics and Computational Intelligence
Study Overview
Status
Intervention / Treatment
Detailed Description
The objective of this project is to develop new techniques to incorporate genomic data into pharmacodynamic models to improve the dosing of chronically administered drugs. Specifically, the investigators look to improve warfarin therapy by decreasing the variability in the effect of this drug using information about the subjects genotype and computational intelligence. The investigators propose to achieve our objectives using a prospective, randomized, controlled clinical trial of a computer program that they will develop from both historical and prospective data. This computer program will be tested against a control group using standard warfarin dosing, and a group using standard dosing plus subject genotype. Warfarin dose and response data will be obtained from patients seen in the Louisville VA anticoagulation clinic. Following informed consent, subject genotype for cytochrome P450 allele 2C9 (2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) will be determined. Other data routinely obtained to aid in warfarin dosing will also be recorded. Using this information, the investigators will develop many different models for warfarin dosing using incrementally more information. Each of these models will be tested using computer simulation until they have obtained the best model. This model will be used in a pilot study to test performance in real time. The results of the pilot study will then be used to power a final clinical trial of standard dosing, standard dosing and genetic information, computer dosing, and computer dosing plus genetic information.
The specific aims of this research are:
- Determine the structure and the type of neural network model for predictions from historically obtained data. (Computer Model)
- Prospectively develop an individualized neural network and nonlinear mixed effect modelling (NONMEM) model capable of predicting erythropoietin dosing for chronic in-center hemodialysis patients using adaptive techniques.
- Develop computer programs based on neural computing that can be used in a clinical setting. (Computer Model)
- Determine the utility of the computer programs prospectively in the clinical setting.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Kentucky
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Louisville, Kentucky, United States, 40206
- VA Medical Center, Louisville
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Warfarin therapy
- Attend anticoagulation clinic
- Warfarin therapy for 6 months
Exclusion Criteria:
- History of non-compliance
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Health Services Research
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Active Comparator: Genomics
Aim 1: Collect historical data on warfarin dosing in subjects at the VA. Aim 2: Collect genotype information on up to 300 subjects receiving warfarin anticoagulation. Aim 3: Develop a computer model incorporating the information from Aim 1 and 2. Aim 4: Conduct randomized clinical trial. |
Model predictive control is a computer based algorithm that can be applied to drug dosing.
This computer tool uses a model of how a patient will respond to a drug dose based on demographic and historical dosing information to predict a new drug response.
A drug dose controller applies all possible doses to the response model and selects the one dose that best meets the stated goals of the drug therapy.
In the case of warfarin, we will calculate an international normalized ratio (INR) value within a specific target range.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Patient Genomics
Time Frame: Baseline
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During Aim 2, Determined Patient Genotypes: CYP2C9 and VKORC1.
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Baseline
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Collaborators and Investigators
Investigators
- Principal Investigator: Michael E. Brier, PhD, VA Medical Center, Louisville
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CAMM-04-07S
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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