Effectiveness of Physiologic Testing in PPI Non-Responders

NCT03202537 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: STU00204123
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

The prevalence of GERD is estimated to be as high as 20% in the US, and up to 50% remain symptomatic on proton pump inhibitor (PPI) therapy. The clinical approach to understand the mechanism of nonresponse is not standardized, and patients will often undergo various tests: 1) pH-impedance, 2) wireless pH monitoring over 96 hours, 3) high-resolution impedance manometry (HRIM), and 4) mucosal impedance (MI). Controversy exists regarding the best technique, optimal study protocol and treatment approach for the PPI non-responder (PPINR) group, resulting in inappropriate resource utilization and a failure to provide effective personalized care. The first aim is to identify the relevant physiologic parameters of diagnostic tools in their ability to predict PPI requirement. In Aim Two, these results will be applied to guide the formal development of a clinical algorithm for the management of PPINRs with personalized clinical pathways based on mechanism of treatment failure. We will first perform a prospective comparison trial of 240 PPINR subjects at 2 sites over 4 years. Subjects will complete symptom questionnaires and undergo diagnostic testing (pH-impedance on PPI therapy, HRIM, 96-hr wireless pH monitoring off PPI therapy and MI). Those who have a positive pH study and/or resume PPI therapy will receive escalation of therapy with dexlansoprazole. We will compare the ability of 96-hr wireless pH monitoring vs pH impedance to predict PPI requirement and response to dexlansoprazole, respectively. We will explore whether MI is equivalent to 96-hr wireless pH monitoring in predicting PPI requirement. Lastly, we will determine whether HRIM metrics can be utilized to determine reflux burden, mechanism and response to treatment. Next, the investigators will develop quality measures for reflux testing in order to develop a simplified management strategy for the PPINR group. The RAND/UCLA Appropriateness Methodology will be utilized with an expert working group to develop formal validated quality measures for reflux testing.

Conditions

Gastro Esophageal Reflux

Outcome Measures

Primary Outcomes (1)

• number of patients able to successfully withdraw from PPI treatment

  ability of 96 hour pH wireless vs pH impedance to predict PPI requirement

  4.5 years

Study Arms (1)

dexlansoprazole

EXPERIMENTAL

dexlansoprazole 90mg per day (60mg am, 30mg pm dosing) for 4 weeks

Drug: dexlansoprazole

Interventions

dexlansoprazole DRUG

dexlansoprazole treatment for Gastroesophageal Reflux symptoms

Also known as: Dexilant

dexlansoprazole

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged 18-80 years old (females of childbearing potential should be on highly effective contraceptive methods)
• Mentally capable to provide informed consent in English
• Present to the Northwestern Medical Group GI practice or the Washington University Division of Gastroenterology with symptoms of GERD (heartburn, regurgitation, and non-cardiac chest pain)
• Have failed an appropriate compliant trial of PPI therapy with a GERD-Q score ≥8.
• Able to undergo endoscopy, ambulatory reflux monitoring, manometry, PPI therapy cessation and trial of dexlansoprazole therapy. Subjects with Los Angeles Classification Grade A (mild) or B esophagitis and symptomatic, non-erosive disease will be enrolled.

You may not qualify if:

• Participation in a concurrent clinical trial or completed another trial within past 8 weeks.
• Active severe erosive esophagitis (Los Angeles Grade C or D), long-segment Barrett's esophagus (Zap score of 4)
• Eosinophilic esophagitis
• Prior gastrointestinal surgery of the esophagus and/or stomach
• Current treatment with dexlansoprazole
• Current signs or symptoms of heart disease. All patients with non-cardiac chest pain are required to have a cardiologist evaluation as standard of care work up in the evaluation of non-cardiac chest pain.
• Subjects with clinically abnormal results of the screening ECG and/or chemistry panel (particularly prolonged QTc interval or hypomagnesaemia) excluded from the dexlansoprazole trial. Subjects with sensitivities or allergies to the metals contained in the Bravo capsule including chromium, nickel, copper, cobalt, and iron.
• Unstable medical illness with ongoing diagnostic work-up and treatment. Patients with well-controlled hypertension, diabetes and a remote history of ischemic heart disease that is deemed stable, as judged by the investigator can be included.
• History of drug addiction, drug abuse or alcoholism.
• Current neurologic or cognitive impairment, which would preclude ability to obtain informed consent.
• Pregnant patients.
• Patients with Cirrhosis (Childs Classification A-C).Special vulnerable populations including children, prisoners, institutionalized individuals.
• Bleeding disorder or requirement of NSAID/aspirin during monitoring period.
• Drugs that affect gastrointestinal symptoms (H2 blockers, antacids, metoclopramide, domperidone, erythromycin, anticholinergics \[bentyl, levsin, belladonna etc.\]). Antidepressants can be continued at stable dose.
• Drugs listed on the Dexilant label including antiretrovirals (Rilpivirine-containing products, Atazanavir, Nelfinavir, Saquinavir, etc), Warfarin, Methotrexate, Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole), Tacrolimus, CYP2C19 or CYP3A4 Inducers or inhibitors.

Sponsors & Collaborators

• Northwestern University: lead
• Washington University School of Medicine: collaborator
• Vanderbilt University: collaborator

Study Sites (1)

Northwestern Memorial Health Care

Chicago, Illinois, 60611, United States

Location

Related Publications (3)

• Gyawali CP, Rogers BD, Yadlapati R, Roman S, Carlson DA, Pandolfino J. pH Impedance Monitoring on Proton Pump Inhibitor Therapy Impacts Management Decisions in Proven GERD but Not in Unproven GERD. Clin Gastroenterol Hepatol. 2025 Dec;23(13):2459-2467. doi: 10.1016/j.cgh.2025.02.032. Epub 2025 May 16.

  PMID: 40383216 DERIVED

• Yadlapati R, Gyawali CP, Masihi M, Carlson DA, Kahrilas PJ, Nix BD, Jain A, Triggs JR, Vaezi MF, Kia L, Kaizer A, Pandolfino JE. Optimal Wireless Reflux Monitoring Metrics to Predict Discontinuation of Proton Pump Inhibitor Therapy. Am J Gastroenterol. 2022 Oct 1;117(10):1573-1582. doi: 10.14309/ajg.0000000000001871. Epub 2022 Jun 10.

  PMID: 35973148 DERIVED

• Yadlapati R, Masihi M, Gyawali CP, Carlson DA, Kahrilas PJ, Nix BD, Jain A, Triggs JR, Vaezi MF, Kia L, Kaizer A, Pandolfino JE. Ambulatory Reflux Monitoring Guides Proton Pump Inhibitor Discontinuation in Patients With Gastroesophageal Reflux Symptoms: A Clinical Trial. Gastroenterology. 2021 Jan;160(1):174-182.e1. doi: 10.1053/j.gastro.2020.09.013. Epub 2020 Sep 16.

  PMID: 32949568 DERIVED

MeSH Terms

Conditions

Gastroesophageal Reflux

Interventions

Dexlansoprazole

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Lansoprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• John Pandolfino, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 21, 2017
• First Posted: June 28, 2017
• Study Start: July 1, 2017
• Primary Completion: July 31, 2022
• Study Completion: July 31, 2022
• Last Updated: January 12, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)