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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
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development ( US Department of Veterans Affairs )

Study Description
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Brief Summary:
This study will create a computer program that can be used to help dose a drug called warfarin for the prevention of blood clotting. The study will collected specific information about those patients receiving this drug and use that information to create a computer program that will predict the effects of the drug. With this prediction program in place, the investigators can perform a series of "what if I gave this amount of drug" simulations to determine the best dose of drug for that patient. Once the computer programs are developed, the investigators will test the program in patients that actually need this drug. They will also include genetic information into the prediction since it has been shown that this information can affect how well the drug works. Patients will have this genetic information determined during this study.

Condition or disease Intervention/treatment Phase
Venous Thrombosis Atrial Fibrillation Myocardial Infarction Device: Genomics Not Applicable

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:

  1. Determine the structure and the type of neural network model for predictions from historically obtained data. (Computer Model)
  2. 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.
  3. Develop computer programs based on neural computing that can be used in a clinical setting. (Computer Model)
  4. Determine the utility of the computer programs prospectively in the clinical setting.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 175 participants
Allocation: N/A
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Arms and Interventions
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Arm Intervention/treatment
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.

 Device: Genomics
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.


Outcome Measures
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Primary Outcome Measures :
  1. Patient Genomics [ Time Frame: Baseline ]
    During Aim 2, Determined Patient Genotypes: CYP2C9 and VKORC1.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Warfarin therapy
  • Attend anticoagulation clinic
  • Warfarin therapy for 6 months

Exclusion Criteria:

  • History of non-compliance
Contacts and Locations
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Information from the National Library of Medicine

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


Locations
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United States, Kentucky
VA Medical Center, Louisville
Louisville, Kentucky, United States, 40206
Sponsors and Collaborators
US Department of Veterans Affairs
Investigators
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Principal Investigator: Michael E. Brier, PhD VA Medical Center, Louisville
More Information
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Responsible Party: US Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00872079    
Other Study ID Numbers: CAMM-04-07S
First Posted: March 31, 2009    Key Record Dates
Results First Posted: February 24, 2014
Last Update Posted: February 24, 2014
Last Verified: February 2014
Keywords provided by VA Office of Research and Development ( US Department of Veterans Affairs ):
warfarin
pharmacokinetics
pharmacodynamics
Additional relevant MeSH terms:
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Atrial Fibrillation
Myocardial Infarction
Thrombosis
Venous Thrombosis
Infarction
Arrhythmias, Cardiac
Heart Diseases
 Cardiovascular Diseases
Pathologic Processes
Ischemia
Necrosis
Myocardial Ischemia
Vascular Diseases
Embolism and Thrombosis