CYP2C19 Genotype Predictor of Gastric Acid Suppression

CYP2C19 Genotype as a Predictor of Gastric Acid Suppression and Healing of Erosive Esophagitis

If CYP2C19 genotype can predict the efficacy of healing erosive esophagitis and gastric acid secretion in patients taking once a day omeprazole.

Study Overview

• Status: Withdrawn
• Conditions: Esophagitis
• Intervention / Treatment: Drug: Omeprazole

Detailed Description

Proton pump inhibitors are metabolized through the CYP2C19 hepatic enzyme system. Several variant genotypes of this enzyme exist which may lead to decreased, normal or increased metabolism of the proton pump inhibitor. With alteration of metabolism, the degree of gastric acid suppression achieved and efficacy in treating reflux could be affected. For example, Asian populations who have low activity of CYP2C19, commonly need lower doses of proton pump inhibitors to manage gastroesophageal reflux because of more sustained blood levels and availability of the drug. Theoretically, those patients who are rapid metabolizers would receive less effective treatment with proton pump inhibitors

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Age 18 or older
• Have either mild-to-moderate Los Angeles (LA) Classification System grade B, moderately severe LA grade C, or severe LA grade D erosive reflux esophagitis
• Or patients having a clinically indicated pH/impedance monitoring on proton pump inhibitor therapy for indications of gastroesophageal reflux disease.

Exclusion criteria:

• Neoplasm of the esophagus or stomach
• Use of drugs that interfere with CYP2C19 metabolism Diazepam, phenytoin, amitriptyline, clomipramine, clopidogrel Cyclophosphamide, progesterone, fluoxetine, fluvoxamine, ketoconazole Lansoprazole, omeprazole, ticlopidine
• Evidence of active H. pylori infection
• Inability to read due to: Blindness, cognitive dysfunction, or English language illiteracy
• Disorders which predispose to unreliable responses such as Schizophrenia, Alzheimer's disease or significant memory loss

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Omeprazole; Patients will undergo whole blood testing for CYP2C19 genotype and will be started on omeprazole 40 mg once daily in the morning 30 minutes before breakfast. The Mayo Dysphasia Questionnaire 30 day (MDQ-30day) will be used during the study. At the end of 8 weeks, patients will undergo dual probe pH/impedance testing on therapy and a clinically indicated endoscopy to rule out Barrett's esophagus and assess healing. CYP2C19 genotyping will be performed in the Mayo laboratory.

Drug: Omeprazole; Patients with LA Grade B-D erosive esophagitis identified at the time of endoscopy will be prospectively recruited. Patients will undergo whole blood testing for CYP2C19 genotype and will be started on omeprazole 40 mg once daily in the morning 30 minutes before breakfast. The Mayo Dysphasia Questionnaire -30 day (MDQ-30day) will be used during the study. At the end of 8 weeks, patients will undergo dual probe pH/impedance testing on therapy and a clinically indicated endoscopy to rule out Barrett's esophagus and assess healing. CYP2C19 genotyping will be performed in the Mayo laboratory.; Other Names: Prilosec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The correlation specific to CYP2C19 genotype with gastric acid suppression by omeprazole.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess patients gastrointestinal symptoms, in patients with EoE by means of standard validated questionnaires	trouble swallowing, heartburn, acid regurgitation	30 days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: David Katzka, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2013
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: March 27, 2013
• First Submitted That Met QC Criteria: April 1, 2013
• First Posted (Estimate): April 4, 2013

Study Record Updates

• Last Update Posted (Actual): October 11, 2017
• Last Update Submitted That Met QC Criteria: October 9, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Esophagitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Esophageal Diseases; Esophagitis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: 12-008053