Gastro Esophageal RefluxEarly Phase 1NCT03202537
Effectiveness of Physiologic Testing in PPI Non-Responders
A Early Phase 1 study testing dexlansoprazole in people with Gastro Esophageal Reflux, run by Northwestern University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Gastro Esophageal Reflux
- What is being tested?
- dexlansoprazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2017to 31 Jul 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- Patients found to have achalasia, a spastic disorder, hypercontractile disorder or functional obstruction at the esophagogastric junction will be excluded. Subjects with a history of structuring or narrowing upon endoscopy (Subjects with no such history will be enrolled; however, if such features are noted upon endoscopy during the study, these subjects will not undergo MI testing).
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern Memorial Health Care
Chicago, Illinois, 60611
About this study
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.
Read the detailed description
The prevalence of gastroesophageal reflux disease is estimated to be as high as 20% in the United States, and up to 50% of these patients remain symptomatic on proton pump inhibitor (PPI) therapy. Unfortunately, the clinical approach to understand the mechanism of nonresponse is not standardized, and patients will often undergo various esophageal function tests: 1) pH-impedance, 2) wireless pH monitoring over 96 hours, 3) high-resolution impedance manometry (HRIM), and 4) mucosal impedance. Currently significant 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. As such, PPINRs contribute to a large healthcare burden in the United States.
The first aim of the study is to identify the relevant physiologic parameters of the aforementioned diagnostic tools in their ability to predict PPI requirement. Subsequently, 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.
The investigators will first perform a prospective comparison trial of 240 PPINR subjects at two centers over a 4 year period. Subjects will complete symptom questionnaires and undergo diagnostic testing (pH-impedance on PPI therapy, HRIM, 96-hthe wireless pH monitoring off of PPI therapy and mucosal impedance). Those who have a positive pH study and/or resume PPI therapy will receive escalation of acid suppression therapy with dexlansoprazole. Experiments 1a \& 1b will compare the ability of 96-hthe wireless pH monitoring vs pH impedance to predict PPI requirement and response to dexlansoprazole, respectively. Experiment 1c will explore whether mucosal impedance is equivalent to 96-hthe wireless pH monitoring in predicting PPI requirement. Lastly, Experiment 1d 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 based on results from aim 1 in addition to the available literature \& evidence. This will be conducted over twelve months (years 4 to 5).
- Conditions
- Gastro Esophageal Reflux
- Being tested
- dexlansoprazole
- Medical subject headings
- Gastroesophageal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dexlansoprazoleDrug
Also called Dexilant
dexlansoprazole treatment for Gastroesophageal Reflux symptoms
| Study group | Role | What they receive |
|---|---|---|
| dexlansoprazole | Experimental | dexlansoprazole 90mg per day (60mg am, 30mg pm dosing) for 4 weeks Receives: Drug: dexlansoprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of patients able to successfully withdraw from PPI treatment
ability of 96 hour pH wireless vs pH impedance to predict PPI requirement
Measured: 4.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2017
- Study start1 Jul 2017
- Primary completion31 Jul 2022
- Study completion31 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Gastro Esophageal RefluxStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 240 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Washington University School of Medicine, Vanderbilt University
- Responsible party
- Principal investigator, John Pandolfino, Northwestern University
- Investigators
- John Pandolfino, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03202537
- Sponsor's protocol ID
- STU00204123
- Status last verified
- Jan 2023
- First submitted
- 21 Jun 2017
- Last updated
- 12 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40383216Yadlapati 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.
PubMed 35973148Yadlapati 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.
PubMed 32949568
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of Physiologic Testing in PPI Non-Responders
- ClinicalTrials.gov ID
- NCT03202537
- Acronym / sponsor ID
- STU00204123
- Conditions
- Gastro Esophageal Reflux
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 240 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- Washington University School of Medicine, Vanderbilt University
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 31 Jul 2022 (actual)
- Study completion
- 31 Jul 2022 (actual)
- First posted
- 28 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The prevalence of gastroesophageal reflux disease is estimated to be as high as 20% in the United States, and up to 50% of these patients remain symptomatic on proton pump inhibitor (PPI) therapy. Unfortunately, the clinical approach to understand the mechanism of nonresponse is not standardized, and patients will often undergo various esophageal function tests: 1) pH-impedance, 2) wireless pH monitoring over 96 hours, 3) high-resolution impedance manometry (HRIM), and 4) mucosal impedance. Currently significant 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. As such, PPINRs contribute to a large healthcare burden in the United States.
The first aim of the study is to identify the relevant physiologic parameters of the aforementioned diagnostic tools in their ability to predict PPI requirement. Subsequently, 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.
The investigators will first perform a prospective comparison trial of 240 PPINR subjects at two centers over a 4 year period. Subjects will complete symptom questionnaires and undergo diagnostic testing (pH-impedance on PPI therapy, HRIM, 96-hthe wireless pH monitoring off of PPI therapy and mucosal impedance). Those who have a positive pH study and/or resume PPI therapy will receive escalation of acid suppression therapy with dexlansoprazole. Experiments 1a \& 1b will compare the ability of 96-hthe wireless pH monitoring vs pH impedance to predict PPI requirement and response to dexlansoprazole, respectively. Experiment 1c will explore whether mucosal impedance is equivalent to 96-hthe wireless pH monitoring in predicting PPI requirement. Lastly, Experiment 1d 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 based on results from aim 1 in addition to the available literature \& evidence. This will be conducted over twelve months (years 4 to 5).
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| dexlansoprazole | Experimental | Drug: dexlansoprazoledexlansoprazole 90mg per day (60mg am, 30mg pm dosing) for 4 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (16 listed)
- 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
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 |
|---|---|---|
| dexlansoprazoleAlso: Dexilantdexlansoprazole treatment for Gastroesophageal Reflux symptoms | Drug | dexlansoprazole |
Primary outcome
number of patients able to successfully withdraw from PPI treatment
Time frame: 4.5 years
ability of 96 hour pH wireless vs pH impedance to predict PPI requirement
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2023.
- Derived from this study: PubMed 40383216Gyawali 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.
- Derived from this study: PubMed 35973148Yadlapati 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.
- Derived from this study: PubMed 32949568Yadlapati 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.
- Individual participant dataSharing planned: No
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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.
John Pandolfino, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing dexlansoprazole in people with Gastro Esophageal Reflux, run by Northwestern University at 1 site 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 5 inclusion and 16 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 12 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
number of patients able to successfully withdraw from PPI treatment (time frame: 4.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03202537, which also lists 3 linked publications.
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 12 Jan 2023.