A Prospective, Observational Study of the PPI Non-responder

NCT03282084 | Withdrawn

• 1 other identifier: D17109
• Study Type: observational
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Gastroesophageal reflux disease (GERD) is a common chronic condition, affecting approximately 20% of the American adult population. Proton pump inhibitors (PPIs) are now the mainstay of medical therapy for symptoms of GERD. Despite their efficacy, several studies have shown that a significant proportion of GERD patients are either partial or non-responders to PPI therapy, defined as symptoms of heartburn and/or regurgitation not relieved by either a standard or double dose of a PPI during a minimum trial of 8 weeks. If GERD symptoms persist, further testing is required. This study will mirror the real world setting to assess the value of published guidelines which recommend specific testing and treatment.

Conditions

Gastro Esophageal Reflux Disease PPI Non-Responders

Outcome Measures

Primary Outcomes (8)

• Objectively evaluate PPI non-responder

  Number of participants with unproven GERD who have reflux esophagitis and eosinophile esophagitis

  8 Weeks after visit 2

• Esophageal acid exposure

  Number and extent of abnormal acid exposure as measured by pH-metry (Bravo capsule) off PPI.

  8 Weeks after visit 2

• Response to different PPI

  Percentage of patients with GERD who fail standard PPI Therapy as documented by wireless pH capsule testing that then respond to an alternative PPI

  8 Weeks after visit 2

• Document the amount of esophageal acid and non-acid exposure in the PPI non-responder patient with proven GERD

  Amount of acid and non-acid exposure in PPI-nonresponder patients with proven GERD as measured by impedance-pH testing on daily PPI therapy.

  8 Weeks after visit 2

• Determine the type, frequency and extent of esophageal motility disorders

  Determine the type, frequency and extent of esophageal motility disorders using HREM (high resolution esophageal manometry) in patients with persistent GERD symptoms despite PPI therapy

  8 Weeks after visit 2

• Nepean Dyspepsia Index

  Using a validated questionnaire determine the prevalence and severity of functional dyspepsia in patients presenting with GERD symptoms using the Nepean Dyspepsia Index.

  8 Weeks after visit 2

• Correlate subjective symptoms of GERD with objective evidence of acid reflux

  Comparison of symptomatic GERD based on GERD-Q validated questionnaire and pH testing

  8 Weeks after visit 2

• Assess overlapping symptoms of dysphagia and GERD

  Assess overlapping symptoms of dysphagia in patients with GERD symptoms who do not respond to empiric PPI therapy using a validated dysphagia questionnaire.

  8 Weeks after visit 2

Study Arms (2)

Unproven GERD

Subjects with no prior testing, normal prior EGD or prior LA Grade A esophagitis

Diagnostic Test: EGD with biopsy

Proven GERD

LA Grade B-D esophagitis, long-segment Barrett's, prior positive pH study

Diagnostic Test: EGD and impedance-pH study on PPI

Interventions

EGD with biopsy DIAGNOSTIC_TEST

Stop PPI and schedule for EGD with biopsy and Wireless pH capsule testing for 7-10 days later. Consider gastric emptying scan or high resolution esophageal manometry

Also known as: Wireless pH Capsule

Unproven GERD

EGD and impedance-pH study on PPI DIAGNOSTIC_TEST

Continue PPI and schedule EGD and Impedance-pH study on PPI. Consider gastric emptying scan or high resolution esophageal manometry

Proven GERD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with persistent GERD symptoms despite treatment with a minimum of 8 weeks daily PPI.

You may qualify if:

• Willing and able to sign informed consent
• Persistent GERD symptoms after minimum 8 week trial on daily PPI

You may not qualify if:

• Unwilling to sign informed consent
• Prior anti-reflux surgery

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Related Publications (13)

• Locke GR 3rd, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology. 1997 May;112(5):1448-56. doi: 10.1016/s0016-5085(97)70025-8.

  PMID: 9136821 BACKGROUND

• Nebel OT, Fornes MF, Castell DO. Symptomatic gastroesophageal reflux: incidence and precipitating factors. Am J Dig Dis. 1976 Nov;21(11):953-6. doi: 10.1007/BF01071906.

  PMID: 984016 BACKGROUND

• El-Serag H, Becher A, Jones R. Systematic review: persistent reflux symptoms on proton pump inhibitor therapy in primary care and community studies. Aliment Pharmacol Ther. 2010 Sep;32(6):720-37. doi: 10.1111/j.1365-2036.2010.04406.x.

  PMID: 20662774 BACKGROUND

• Richter JE. How to manage refractory GERD. Nat Clin Pract Gastroenterol Hepatol. 2007 Dec;4(12):658-64. doi: 10.1038/ncpgasthep0979.

  PMID: 18043675 BACKGROUND

• Cicala M, Emerenziani S, Guarino MP, Ribolsi M. Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease. World J Gastroenterol. 2013 Oct 21;19(39):6529-35. doi: 10.3748/wjg.v19.i39.6529.

  PMID: 24151377 BACKGROUND

• Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013 Mar;108(3):308-28; quiz 329. doi: 10.1038/ajg.2012.444. Epub 2013 Feb 19. No abstract available.

  PMID: 23419381 BACKGROUND

• Dickman R, Boaz M, Aizic S, Beniashvili Z, Fass R, Niv Y. Comparison of clinical characteristics of patients with gastroesophageal reflux disease who failed proton pump inhibitor therapy versus those who fully responded. J Neurogastroenterol Motil. 2011 Oct;17(4):387-94. doi: 10.5056/jnm.2011.17.4.387. Epub 2011 Oct 31.

  PMID: 22148108 BACKGROUND

• Lee WC, Yeh YC, Lacy BE, Pandolfino JE, Brill JV, Weinstein ML, Carlson AM, Williams MJ, Wittek MR, Pashos CL. Timely confirmation of gastro-esophageal reflux disease via pH monitoring: estimating budget impact on managed care organizations. Curr Med Res Opin. 2008 May;24(5):1317-27. doi: 10.1185/030079908x280680. Epub 2008 Mar 27.

  PMID: 18377705 BACKGROUND

• Miller SM, Goldstein JL, Gerson LB. Cost-effectiveness model of endoscopic biopsy for eosinophilic esophagitis in patients with refractory GERD. Am J Gastroenterol. 2011 Aug;106(8):1439-45. doi: 10.1038/ajg.2011.94. Epub 2011 Mar 29.

  PMID: 21448144 BACKGROUND

• Charbel S, Khandwala F, Vaezi MF. The role of esophageal pH monitoring in symptomatic patients on PPI therapy. Am J Gastroenterol. 2005 Feb;100(2):283-9. doi: 10.1111/j.1572-0241.2005.41210.x.

  PMID: 15667483 BACKGROUND

• Mainie I, Tutuian R, Shay S, Vela M, Zhang X, Sifrim D, Castell DO. Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: a multicentre study using combined ambulatory impedance-pH monitoring. Gut. 2006 Oct;55(10):1398-402. doi: 10.1136/gut.2005.087668. Epub 2006 Mar 23.

  PMID: 16556669 BACKGROUND

• Quigley EM, Lacy BE. Overlap of functional dyspepsia and GERD--diagnostic and treatment implications. Nat Rev Gastroenterol Hepatol. 2013 Mar;10(3):175-86. doi: 10.1038/nrgastro.2012.253. Epub 2013 Jan 8.

  PMID: 23296247 BACKGROUND

• Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L; American College of Gastroenterology. Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2013 Jan;108(1):18-37; quiz 38. doi: 10.1038/ajg.2012.373. Epub 2012 Nov 13.

  PMID: 23147521 BACKGROUND

MeSH Terms

Interventions

Endoscopy, Digestive System; Biopsy

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Specimen Handling; Investigative Techniques

Study Officials

• Brian E Lacy, MD, PhD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2017
• First Posted: September 13, 2017
• Study Start: June 20, 2017
• Primary Completion: June 15, 2018
• Study Completion: June 15, 2018
• Last Updated: April 2, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share