Personalized Warfarin Dosing by Genomics and Computational Intelligence
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|ClinicalTrials.gov Identifier: NCT00872079|
Recruitment Status : Terminated (Lack of Funding)
First Posted : March 31, 2009
Results First Posted : February 24, 2014
Last Update Posted : February 24, 2014
|Condition or disease||Intervention/treatment||Phase|
|Venous Thrombosis Atrial Fibrillation Myocardial Infarction||Device: Genomics||Not Applicable|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||175 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Health Services Research|
|Official Title:||Personalized Warfarin Dosing Using Genomics and Computational Intelligence|
|Study Start Date :||September 2008|
|Actual Primary Completion Date :||September 2011|
|Actual Study Completion Date :||September 2011|
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.
- Patient Genomics [ Time Frame: Baseline ]During Aim 2, Determined Patient Genotypes: CYP2C9 and VKORC1.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00872079
|United States, Kentucky|
|VA Medical Center, Louisville|
|Louisville, Kentucky, United States, 40206|
|Principal Investigator:||Michael E. Brier, PhD||VA Medical Center, Louisville|