Gastroesophageal Reflux DiseaseNCT02930824
Genotype-supported Versus Conventional Proton Pump Inhibitor Dosing
A study testing CYP2C19 genotyping in people with Gastroesophageal Reflux Disease, run by University of Florida at 2 sites in United States.
Trial summary
Investigators will conduct a comparative effectiveness study of genotype-supported vs. conventional PPI dosing. Adults and children presenting with Gastroesophageal Reflux Disease (GERD) or dyspepsia symptoms and either 1) being initiated on proton pump inhibitor (PPI) therapy or 2) with continued symptoms on current… Read more about this study
- Who is it for?
- Ages 5 to 100 years
- Conditions the study is for
- Gastroesophageal Reflux Disease
- What is being tested?
- CYP2C19 genotyping
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 185 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2016to 17 Jul 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 5-17 years of age
- diagnosed with GERD or any other stomach acid mediated condition for which a PPI treatment is provided
- currently under a Proton Pump Inhibitor (PPI) therapy or will start a PPI therapy
- Parents/legal guardians and or child must have access to internet and a valid email address
- 18 years of age or older
- Gastroesophageal Reflux Disease symptoms
- Being initiated on PPI therapy OR continues to have symptoms despite PPI therapy
Who cannot join
- history of extensive esophageal or gastric surgery
- diagnosed with any major chronic illness or conditions that in the opinion of the gastroenterologist that would interfere with participation in the study
- history of Phenylketonuria (PKU) and patients with a history of previous adverse effects from PPI treatment or sensitivity to aspartame (NutraSweet, Equal)
- Adult:
- Extensive esophageal or gastric surgery
- Any chronic illness that would interfere with the study
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Florida
Gainesville, Florida, 32610
Nemours Children's Hospital
Orlando, Florida, 32827
About this study
Official title: Implementing Genomics in Practice (IGNITE) Proof of Concept Study: CYP2C19 Genotype-supported Versus Conventional Proton Pump Inhibitor Dosing
Investigators will conduct a comparative effectiveness study of genotype-supported vs. conventional PPI dosing. Adults and children presenting with Gastroesophageal Reflux Disease (GERD) or dyspepsia symptoms and either 1) being initiated on proton pump inhibitor (PPI) therapy or 2) with continued symptoms on current PPI therapy will be recruited from gastroenterology clinics and randomized to a genotype-supported versus conventional PPI therapy management strategy.
Read the detailed description
The efficacy of proton pump inhibitors (PPIs) is highly dependent on plasma concentrations achieved following drug administration. All PPIs are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Depending on the CYP2C19 genotype, individuals are classified into different metabolizer phenotypes: poor metabolizers (PM, 2 loss-of-function CYP2C19 alleles); intermediate metabolizers (IM, one loss-of-function allele); normal metabolizers (NM, no loss or gain-of-function alleles); rapid metabolizer (RM; one gain-of-function allele) and ultra-rapid metabolizers (UM, two gain-of function-alleles). Genetic variants in CYP2C19 are known to profoundly influence PPI plasma concentrations and consequently, response to PPI therapy. For example, individuals classified as either RM or UM have lower PPI concentrations compared to NM or loss-of-function (LOF) allele carriers, respond poorly to PPI therapy, and some fail to respond even when the PPI dose is increased. The investigators hypothesize that genotype-supported PPI dosing will lead to better GERD control and improvement in severity of dyspepsia symptoms compared to conventional dosing. The investigators will conduct a comparative effectiveness study of genotype-supported vs. conventional PPI dosing. Patients presenting with GERD or dyspepsia symptoms and either 1) being initiated on PPI therapy or 2) with continued symptoms on current PPI therapy will be recruited from gastroenterology clinics and randomized to a genotype-supported versus conventional PPI therapy management strategy. The investigators will integrate individual CYP2C19 genotype information into dosing decisions for the genotype-supported arm and compare change in symptom control from baseline to the end of the study between study arms. Given that PPI efficacy is related to PPI exposure and to metabolizer phenotype, individualizing treatment using CYP2C19 genotype-supported dosing is expected to improve symptom management. The investigators will also evaluate patient and clinician knowledge and attitudes about pharmacogenetics testing and physician acceptance of genetic information into clinical practice. Finally, the investigators will collect preliminary data on the potential impact of CYP2C19-supported PPI dosing on adverse event rates.
- Conditions
- Gastroesophageal Reflux Disease
- Being tested
- CYP2C19 genotyping
- Medical subject headings
- Gastroesophageal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CYP2C19 genotypingGenetic
All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.
| Study group | Role | What they receive |
|---|---|---|
| Adult Genotype guided treatment | Experimental | For adults randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. Receives: Genetic: CYP2C19 genotyping |
| Adult Conventional treatment | No intervention | For adults randomized to the conventional arm no genotype will be provided to physicians to assist in dosing. |
| Pediatric Genotype guided treatment | Experimental | For children randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. Receives: Genetic: CYP2C19 genotyping |
| Pediatric Conventional treatment | No intervention | For children randomized to the conventional arm no genotype will be provided to physicians to assist in dosing. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reflux Disease Questionnaire (RDQ)
The RDQ was developed to monitor treatment response over time and evaluates 6 symptoms (12 items) covering 3 domains: heartburn, regurgitation, and upper abdominal pain. Each symptom is evaluated using a 6-point Likert scale to assess frequency and severity over the previous week. Each symptom is rated from 1 (did not have) to 6 (severe), and the RDQ mean score is calculated as the mean response to the 12 items. The RDQ mean score thus ranges from 1 to 6 and has been psycho-metrically validated.
Measured: Change from baseline and 12 weeks
Pediatric Sinonasal Symptom Survey (SN-5)
The Pediatric Sinonasal Symptom Survey (SN-5) is a validated 5-item scale with each item rated on a scale of worsening symptoms from 1 (none of the time) through 7 (all of the time). Items were averaged to yield a single total score ranging from 1 (better outcomes) to 7 (worse outcomes). The total SN-5 scores were compared between the conventional and genotype-guided dosing groups to determine if one group reported worsening symptoms over the other.
Measured: Week 4 (or next available results)
Safety Questionnaire (SafetyQ)
Occurrence of adverse events over the 12 weeks was captured by the Safety Questionnaire (SafetyQ), which was to be completed on a weekly basis by the parents. The Safety Questionnaire (SafetyQ) asked about the presence of seven different respiratory symptoms since their last visit; upper respiratory infection, sore throat, strep throat, bronchitis, pneumonia, ear infection, and acute sinusitis. If a symptom was selected as being present since the last visit, the date of onset and patient-reported explanation of the symptom was recorded. The number of participants who reported infections were compared between each group.
Measured: Over the 12-week period or last date of follow-up
Gastroesophageal Reflux Disease (GERD) Assessment of Symptoms in Pediatrics Questionnaire (Gasp-Q)
Gastroesophageal reflux disease (GERD) Assessment of Symptoms in Pediatrics Questionnaire (Gasp-Q) is a validated patient-reported outcome questionnaire that evaluated proton pump inhibitor therapy efficacy. Gasp-Q inquired about the severity and frequency of belly pain, chest pain, difficulty swallowing, choking, burping, nausea, pain after eating, night pain, and vomiting. If the symptom was present, the patient was asked to score the severity of the symptom ranging from 1 (Not at all severe) to 7 (Most severe). A composite score was then calculated based on the scoring of the 9 symptoms and ranged from 9 to 63.
Measured: Change in score from baseline to the week 4 ± 1-week
Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Module
Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Module is a validated patient-reported outcome questionnaire and Likert response scale, to evaluate proton pump inhibitor therapy efficacy. The gastrointestinal problems included in the PedsQL were stomach pain and hurt, stomach upset, food and drink limits, trouble swallowing, heartburn and reflux, gas and bloating, constipation, diarrhea, and worry. Participants were asked to rate the symptoms from 0 (never a problem) to 4 (almost always a problem).
Measured: Change in score from baseline to the week 4 ± 1-week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2016 (estimated)
- Study startDec 2016
- Primary completion17 Jul 2019
- Study completion17 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gastroesophageal Reflux DiseaseStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 185 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Nemours Children's Hospital, National Human Genome Research Institute (NHGRI)
- Responsible party
- Sponsor
- Investigators
- Larisa Cavallari, PharmD, Principal investigator, University of FloridaJames P Franciosi, MD, Principal investigator, Nemours Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02930824
- Sponsor's protocol ID
- IRB201601774-N
- Other IDs
- U01HG007269
- Status last verified
- May 2024
- First submitted
- 10 Oct 2016
- Last updated
- 16 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Implementing Genomics in Practice (IGNITE) Proof of Concept Study: CYP2C19 Genotype-supported Versus Conventional Proton Pump Inhibitor Dosing
- ClinicalTrials.gov ID
- NCT02930824
- Acronym / sponsor ID
- IRB201601774-N
- Conditions
- Gastroesophageal Reflux Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 185 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Nemours Children's Hospital, National Human Genome Research Institute (NHGRI)
- Study start
- Dec 2016 (actual)
- Primary completion
- 17 Jul 2019 (actual)
- Study completion
- 17 Jul 2019 (actual)
- First posted
- 12 Oct 2016 (estimated)
- Results
- Posted 21 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigators will conduct a comparative effectiveness study of genotype-supported vs. conventional PPI dosing. Adults and children presenting with Gastroesophageal Reflux Disease (GERD) or dyspepsia symptoms and either 1) being initiated on proton pump inhibitor (PPI) therapy or 2) with continued symptoms on current PPI therapy will be recruited from gastroenterology clinics and randomized to a genotype-supported versus conventional PPI therapy management strategy.
Detailed description
The efficacy of proton pump inhibitors (PPIs) is highly dependent on plasma concentrations achieved following drug administration. All PPIs are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Depending on the CYP2C19 genotype, individuals are classified into different metabolizer phenotypes: poor metabolizers (PM, 2 loss-of-function CYP2C19 alleles); intermediate metabolizers (IM, one loss-of-function allele); normal metabolizers (NM, no loss or gain-of-function alleles); rapid metabolizer (RM; one gain-of-function allele) and ultra-rapid metabolizers (UM, two gain-of function-alleles). Genetic variants in CYP2C19 are known to profoundly influence PPI plasma concentrations and consequently, response to PPI therapy. For example, individuals classified as either RM or UM have lower PPI concentrations compared to NM or loss-of-function (LOF) allele carriers, respond poorly to PPI therapy, and some fail to respond even when the PPI dose is increased. The investigators hypothesize that genotype-supported PPI dosing will lead to better GERD control and improvement in severity of dyspepsia symptoms compared to conventional dosing. The investigators will conduct a comparative effectiveness study of genotype-supported vs. conventional PPI dosing. Patients presenting with GERD or dyspepsia symptoms and either 1) being initiated on PPI therapy or 2) with continued symptoms on current PPI therapy will be recruited from gastroenterology clinics and randomized to a genotype-supported versus conventional PPI therapy management strategy. The investigators will integrate individual CYP2C19 genotype information into dosing decisions for the genotype-supported arm and compare change in symptom control from baseline to the end of the study between study arms. Given that PPI efficacy is related to PPI exposure and to metabolizer phenotype, individualizing treatment using CYP2C19 genotype-supported dosing is expected to improve symptom management. The investigators will also evaluate patient and clinician knowledge and attitudes about pharmacogenetics testing and physician acceptance of genetic information into clinical practice. Finally, the investigators will collect preliminary data on the potential impact of CYP2C19-supported PPI dosing on adverse event rates.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Adult Genotype guided treatment | Experimental | Genetic: CYP2C19 genotypingFor adults randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. |
| Adult Conventional treatment | No intervention | –For adults randomized to the conventional arm no genotype will be provided to physicians to assist in dosing. |
| Pediatric Genotype guided treatment | Experimental | Genetic: CYP2C19 genotypingFor children randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. |
| Pediatric Conventional treatment | No intervention | –For children randomized to the conventional arm no genotype will be provided to physicians to assist in dosing. |
Who may qualify
- Ages
- 5 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 5-17 years of age
- diagnosed with GERD or any other stomach acid mediated condition for which a PPI treatment is provided
- currently under a Proton Pump Inhibitor (PPI) therapy or will start a PPI therapy
- Parents/legal guardians and or child must have access to internet and a valid email address
- 18 years of age or older
Key exclusion criteria (6 listed)
- history of extensive esophageal or gastric surgery
- diagnosed with any major chronic illness or conditions that in the opinion of the gastroenterologist that would interfere with participation in the study
- history of Phenylketonuria (PKU) and patients with a history of previous adverse effects from PPI treatment or sensitivity to aspartame (NutraSweet, Equal)
- Extensive esophageal or gastric surgery
- Any chronic illness that would interfere with the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CYP2C19 genotypingAll proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced. | Genetic | Adult Genotype guided treatment, Pediatric Genotype guided treatment |
Primary outcome
Reflux Disease Questionnaire (RDQ)
Time frame: Change from baseline and 12 weeks
The RDQ was developed to monitor treatment response over time and evaluates 6 symptoms (12 items) covering 3 domains: heartburn, regurgitation, and upper abdominal pain. Each symptom is evaluated using a 6-point Likert scale to assess frequency and severity over the previous week. Each symptom is rated from 1 (did not have) to 6 (severe), and the RDQ mean score is calculated as the mean response to the 12 items. The RDQ mean score thus ranges from 1 to 6 and has been psycho-metrically validated.
Pediatric Sinonasal Symptom Survey (SN-5)
Time frame: Week 4 (or next available results)
The Pediatric Sinonasal Symptom Survey (SN-5) is a validated 5-item scale with each item rated on a scale of worsening symptoms from 1 (none of the time) through 7 (all of the time). Items were averaged to yield a single total score ranging from 1 (better outcomes) to 7 (worse outcomes). The total SN-5 scores were compared between the conventional and genotype-guided dosing groups to determine if one group reported worsening symptoms over the other.
Safety Questionnaire (SafetyQ)
Time frame: Over the 12-week period or last date of follow-up
Occurrence of adverse events over the 12 weeks was captured by the Safety Questionnaire (SafetyQ), which was to be completed on a weekly basis by the parents. The Safety Questionnaire (SafetyQ) asked about the presence of seven different respiratory symptoms since their last visit; upper respiratory infection, sore throat, strep throat, bronchitis, pneumonia, ear infection, and acute sinusitis. If a symptom was selected as being present since the last visit, the date of onset and patient-reported explanation of the symptom was recorded. The number of participants who reported infections were compared between each group.
Gastroesophageal Reflux Disease (GERD) Assessment of Symptoms in Pediatrics Questionnaire (Gasp-Q)
Time frame: Change in score from baseline to the week 4 ± 1-week
Gastroesophageal reflux disease (GERD) Assessment of Symptoms in Pediatrics Questionnaire (Gasp-Q) is a validated patient-reported outcome questionnaire that evaluated proton pump inhibitor therapy efficacy. Gasp-Q inquired about the severity and frequency of belly pain, chest pain, difficulty swallowing, choking, burping, nausea, pain after eating, night pain, and vomiting. If the symptom was present, the patient was asked to score the severity of the symptom ranging from 1 (Not at all severe) to 7 (Most severe). A composite score was then calculated based on the scoring of the 9 symptoms and ranged from 9 to 63.
Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Module
Time frame: Change in score from baseline to the week 4 ± 1-week
Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Module is a validated patient-reported outcome questionnaire and Likert response scale, to evaluate proton pump inhibitor therapy efficacy. The gastrointestinal problems included in the PedsQL were stomach pain and hurt, stomach upset, food and drink limits, trouble swallowing, heartburn and reflux, gas and bloating, constipation, diarrhea, and worry. Participants were asked to rate the symptoms from 0 (never a problem) to 4 (almost always a problem).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Larisa Cavallari, PharmD principal investigator
University of Florida
James P Franciosi, MD principal investigator
Nemours Children's Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CYP2C19 genotyping in people with Gastroesophageal Reflux Disease, run by University of Florida at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reflux Disease Questionnaire (RDQ) (time frame: Change from baseline and 12 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.