Implementation of PPI Medication PGX Testing (PGX)

October 24, 2018 updated by: James Franciosi, Nemours Children's Clinic

Implementation of Pharmacogenomic Testing in Nemours Children's Health System

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
28

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Orlando, Florida, United States, 32827
        • Nemours Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: Genotype Guided PPI Dosing
Dosing of PPIs such as Prevacid and Nexium will be recommended based on CYP2C19 genotype information.
Other Names:
  • Nexium
  • Prevacid
  • Prilosec
  • Proton Pump Inhibitor

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Count of Patients Agreeing to Volunteer for the Study
Time Frame: Through 12 months study
Outcomes for evaluating the success of PGX implementation
Through 12 months study
Count of Patients Reporting Efficacy and Toxicity Data
Time Frame: Throughout 12 month study
Outcomes for evaluating the success of PGX implementation
Throughout 12 month study
Count of Providers Agreeing to Participate in Study
Time Frame: Throughout 12 month study
Outcomes for evaluating the success of PGX implementation
Throughout 12 month study
Count of Participants Agreeing to Future Use of DNA
Time Frame: Throughout 12 month study
Outcomes for evaluating the success of PGX implementation
Throughout 12 month study
Adverse Effects After Genotype-guided PPI Therapy
Time Frame: Throughout 12 month study
Count of participants reporting adverse effects after genotype-guided PPI therapy.
Throughout 12 month study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nemours Children's Clinic

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: James P Franciosi, MD, Nemours Children's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 21, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 23, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 27, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 6, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 9, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 21, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 744230

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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