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Implementation of PPI Medication PGX Testing (PGX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02794844
Recruitment Status : Completed
First Posted : June 9, 2016
Results First Posted : May 9, 2018
Last Update Posted : November 21, 2018
Sponsor:
Information provided by (Responsible Party):
James Franciosi, Nemours Children's Clinic

Tracking Information
First Submitted Date  ICMJE April 27, 2016
First Posted Date  ICMJE June 9, 2016
Results First Submitted Date  ICMJE April 9, 2018
Results First Posted Date  ICMJE May 9, 2018
Last Update Posted Date November 21, 2018
Actual Study Start Date  ICMJE July 21, 2016
Actual Primary Completion Date January 23, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 18, 2018)
  • Count of Patients Agreeing to Volunteer for the Study [ Time Frame: Through 12 months study ]
    Outcomes for evaluating the success of PGX implementation
  • Count of Patients Reporting Efficacy and Toxicity Data [ Time Frame: Throughout 12 month study ]
    Outcomes for evaluating the success of PGX implementation
  • Count of Providers Agreeing to Participate in Study [ Time Frame: Throughout 12 month study ]
    Outcomes for evaluating the success of PGX implementation
  • Count of Participants Agreeing to Future Use of DNA [ Time Frame: Throughout 12 month study ]
    Outcomes for evaluating the success of PGX implementation
  • Adverse Effects After Genotype-guided PPI Therapy [ Time Frame: Throughout 12 month study ]
    Count of participants reporting adverse effects after genotype-guided PPI therapy.
Original Primary Outcome Measures  ICMJE
 (submitted: June 6, 2016)
  • Percent of Patients Agreeing to Volunteer for the Study [ Time Frame: Through 12 months study ]
    Outcomes for evaluating the success of PGX implementation
  • Percent of Patients Reporting Efficacy and Toxicity Data [ Time Frame: Throughout 12 month study ]
    Outcomes for evaluating the success of PGX implementation
  • Percent of Providers Agreeing to Participate in Study [ Time Frame: Throughout 12 month study ]
    Outcomes for evaluating the success of PGX implementation
  • Percent of Participants Agreeing to Future Use of DNA [ Time Frame: Throughout 12 month study ]
    Outcomes for evaluating the success of PGX implementation
  • Percent of participants reporting adverse effects before and after genotype-guided PPI therapy [ Time Frame: Throughout 12 month study ]
    Outcome metrics for response to PPI
  • Percent of participants reporting a decrease or increase in clinical symptoms after genotype-guided PPI therapy. [ Time Frame: Throughout 12 month study ]
    Outcome metrics for response to PPI
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Implementation of PPI Medication PGX Testing
Official Title  ICMJE Implementation of Pharmacogenomic Testing in Nemours Children's Health System
Brief Summary Using genetic information about the individual to pick the right drug for the right disease at the right dose defines personalized medicine. This pilot study seeks to institute pharmacogenomic testing, that is identifying genetic variation that influences patient response to drugs, into the Nemours Children's Health system. We propose to initiate the study by identifying genetic differences in cyp2c19, a gene that is responsible for a certain enzyme in the liver that metabolizes many drugs including a class of drugs called proton pump inhibitors (ppi; Prevacid, Nexium). PPIs are used to treat heartburn and other symptoms of gastroesophageal reflux disease (gerd) and are extensively used in pediatrics. Chronic use of PPIs can cause serious side effects including cold, pneumonia and stomach infections, which gets worse at higher doses. Children who poorly metabolize drugs because of genetic variation in cyp2c19 should get lower doses of PPIs than children who metabolize PPIs normally. Our pilot study will genotype children with gerd or other stomach acid mediated conditions for which a PPI is prescribed using a sample of spit to determine which dose of PPI they get based on the form of the cyp2c19 gene they have. We will study 120 children 2-17 yo diagnosed with gastroesophageal reflux disease (gerd) or other stomach acid mediated conditions for which a ppi is prescribed . Genetic results are available in < 60 minutes, and their doses are determined by their doctor based on genetic results. This study will allow us to gain valuable experience that will be used to expand our genetic program to other genes and drugs.
Detailed Description The long-term objective of this research is to implement pharmacogenomic (PGX) testing of approved gene-drug pairs to maximize the efficacy and minimize adverse events for drugs that are used to treat childhood disease. Personalized medicine, that is, the use of the patient's own genetic information to predict the right dose of the right drug, has been a goal of medicine's since the publication of the human genome and HAPMAP projects. However, the adoption of PGX testing has been slow owing to several barriers and challenges. Recently President Obama announced the precision medicine initiative, which includes PGX testing, and has earmarked $ 1 b to implement it. The precision medicine initiative is expected to move personalized medicine forward so that most patients including pediatric patients will benefit. The Nemours Children's Health System is uniquely positioned to lead the effort to personalize medicine among pediatric patients. The goal of the proposed 1-year pilot project is to implement PGX testing in the Nemours children's health system. The experience, knowledge and skills gained in this pilot project will position Nemours to help lead precision medicine initiatives including PGX testing among pediatric populations. To implement PGX testing in Nemours we propose to begin testing the cyp2c19 - proton pump inhibitor gene-drug pair in the division of gastroenterology, Nemours children's hospital. A total of 120 children 2-17 yo who have been diagnosed with gastroesophageal reflux disease (GERD) or other stomach acid mediated conditions for which a PPI is prescribed will be recruited into the study by pediatric gastroenterologists (aim 1a). Drs. Franciosi and Lima will educate staff in the division of PGX testing and of the study. GI pediatricians are not required to participate in PGX testing. After obtaining consent, the study coordinator will obtain and bar code samples of saliva from the patient. Samples will be genotyped by Spartan Rx, a point-of-care genotyping platform, which are housed (2 of them) in the division of pathology. Loss-of-function alleles (*2, *3) and the gain-of-function allele (*17) are identified in < 60 minutes. The result of genotyping will be checked by dr. Badizadegan and entered into the patient's EMR. Clinical Decision Support (CDS) tools will advise Drs. Badizadegan and Franciosi of the patient's metabolic phenotype based on cyp2c19 genotype. Dr. Franciosi (or other GI pediatricians) will decide the dose of PPI to use based CDS tools carrying algorithms for conventional dosing and for genotype-guided dosing of PPIs. The electronic prescription for the PPI with genotype-guided dosing will be called in. PPI efficacy and safety for each study participant will be monitored weekly (aim 1B) by collecting and recording scores on validated GERD and adverse reaction questionnaires. Efficacy and safety scores will be communicated by each participant (or caregiver) using mobile devices (iPhone; computer) and recorded using redcap. Dr. Blake will supervise this phase of the study. Outcome metrics for aim 1A include: % of patients agreeing to volunteer for the study; % of patients reporting efficacy and toxicity data; % of providers agreeing to participate in study; and % of participants agreeing to future use of DNA. Outcome metrics for aim B will be judgments by Dr. Franciosi and his staff regarding success based on scores from GERD and adverse event questionnaires.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Gastroesophageal Reflux
Intervention  ICMJE Drug: Genotype Guided PPI Dosing
Dosing of PPIs such as Prevacid and Nexium will be recommended based on CYP2C19 genotype information.
Other Names:
  • Prilosec
  • Nexium
  • Prevacid
  • Proton Pump Inhibitor
Study Arms  ICMJE Experimental: Genotype Guided PPI Dosing

Genotype Guided PPI Dosing: PI type and dosing will be recommended in real time based on patients' CYP2C19 genotype / metabolizer phenotype.

No other ARM will be studied.

Intervention: Drug: Genotype Guided PPI Dosing
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 9, 2018)
28
Original Estimated Enrollment  ICMJE
 (submitted: June 6, 2016)
120
Actual Study Completion Date  ICMJE August 31, 2018
Actual Primary Completion Date January 23, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Children diagnosed with Gastroesophageal Reflux Disease (GERD) or a stomach acid mediated condition for which a PPI is prescribed.
  • Currently taking or will be prescribed Proton Pump Inhibitor (PPI) medication
  • Parents/legal guardians and or child must also have access to the internet and a valid email address to complete weekly required forms.

Exclusion Criteria:

  • Children who have had peptic ulcer surgery;
  • with a history of PKU
  • with a history of previous adverse effects from PPI treatment or a sensitivity to aspartame (NutraSweet, Equal);
  • who are non-adherent including inability or unwillingness of the legal guardian to provide consent of unwillingness of the child to provide assent;
  • who are unable to take study medications;
  • who are unable to communicate via telephone or other device;
  • who do not have access to a computer with internet access
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02794844
Other Study ID Numbers  ICMJE 744230
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party James Franciosi, Nemours Children's Clinic
Study Sponsor  ICMJE Nemours Children's Clinic
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: James P Franciosi, MD Nemours Children's Hospital
PRS Account Nemours Children's Clinic
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP