Diagnosis of Acid Reflux Disease Using Novel Imaging: A Prospective Study

NCT02081404 | Completed DMC

• 1 other identifier: 3155105
• Study Type: interventional
• Target: 98
• Locations: 2 countries
• Sites: 2

Brief Summary

Gastroesophageal reflux disease (GERD), a common chronic disorder in the veteran population, is associated with drug costs exceeding $ 10 billion/year. Only 30-40% of patients with reflux symptoms have erosive esophagitis. The vast majority suffers from non erosive reflux disease (NERD), a condition in which standard endoscopy fails to identify any mucosal breaks and is unable to confirm the diagnosis. Unfortunately, a gold standard for the diagnosis of NERD does not exist. Narrow band imaging (NBI) utilizes spectral narrow band filters (incorporated into standard endoscopes) and helps to see abnormal areas not identified during standard endoscopy. Preliminary results have shown that NBI endoscopy may represent a significant improvement over standard endoscopy for the diagnosis of NERD. The purpose of this study is to accurately diagnosis non acid reflux disease by using a blue light (also known as NBI)upper endoscopy technique.

Conditions

Non-erosive Reflux Disease

Keywords

Non-erosive Reflux Disease

Outcome Measures

Primary Outcomes (1)

• NBI endoscopy identifies changes in the distal esophagus that are specific for diagnosing patients with Non-Esophageal Reflux Disease.

  1. Proportion of patients with NBI abnormalities in the NERD group vs. controls. 2. Proportion of patients with resolution of NBI abnormalities after PPI therapy.

  10 weeks

Study Arms (2)

Esomeprazole

ACTIVE COMPARATOR

proton pump inhibitor

Drug: Esomeprazole

Placebo

PLACEBO COMPARATOR

placebo

Drug: Placebo

Interventions

Esomeprazole DRUG

standard dose of proton pump inhibitor by mouth once a day for 30 days

Also known as: Nexium

Esomeprazole

Placebo DRUG

placebo

Also known as: inactive substance

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age
• Capable of giving informed consents.
• Cases of NERD will be recruited on the basis of presence of heartburn and/or regurgitation using two validated GERD questionnaires in conjunction with an abnormal esophageal pH result and absence of erosions at standard endoscopy.

You may not qualify if:

• Presence of macroscopic erosive esophagitis
• Pregnancy/lactation
• Chronic anticoagulation
• Patients with significant medical comorbidities (oxygen dependent chronic obstructive pulmonary disease, NYHA class III or IV congestive heart failure, recent diagnosis of cancer with a life-expectancy \< 5 years)
• History of Barrett's esophagus
• Presence of columnar lined distal esophagus on endoscopy with intestinal metaplasia
• Presence of cancer or mass lesion in the esophagus or stomach
• Esophageal strictures
• Peptic ulcer disease and Helicobacter pylori infection
• Prior history of esophageal surgery
• Allergic to PPIs
• Patients on drugs known to cause pill-related esophagitis (e.g. potassium supplements)
• Patients with HIV or other immunocompromised conditions who may have infectious esophagitis
• Eosinophilic esophagitis

Sponsors & Collaborators

• Midwest Biomedical Research Foundation: lead
• Kansas City Veteran Affairs Medical Center: collaborator

Study Sites (2)

Department of Veterans Affairs Medical Center

Kansas City, Missouri, 64128, United States

Location

Queen Medical Center

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (40)

• Sharma P, Wani S, Bansal A, Hall S, Puli S, Mathur S, Rastogi A. A feasibility trial of narrow band imaging endoscopy in patients with gastroesophageal reflux disease. Gastroenterology. 2007 Aug;133(2):454-64; quiz 674. doi: 10.1053/j.gastro.2007.06.006. Epub 2007 Jun 8.

  PMID: 17681166 BACKGROUND

• Dent J, El-Serag HB, Wallander MA, Johansson S. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2005 May;54(5):710-7. doi: 10.1136/gut.2004.051821.

  PMID: 15831922 BACKGROUND

• El-Serag HB. Time trends of gastroesophageal reflux disease: a systematic review. Clin Gastroenterol Hepatol. 2007 Jan;5(1):17-26. doi: 10.1016/j.cgh.2006.09.016. Epub 2006 Dec 4.

  PMID: 17142109 BACKGROUND

• Liu JY, Woloshin S, Laycock WS, Rothstein RI, Finlayson SR, Schwartz LM. Symptoms and treatment burden of gastroesophageal reflux disease: validating the GERD assessment scales. Arch Intern Med. 2004 Oct 11;164(18):2058-64. doi: 10.1001/archinte.164.18.2058.

  PMID: 15477443 BACKGROUND

• McDougall NI, Johnston BT, Kee F, Collins JS, McFarland RJ, Love AH. Natural history of reflux oesophagitis: a 10 year follow up of its effect on patient symptomatology and quality of life. Gut. 1996 Apr;38(4):481-6. doi: 10.1136/gut.38.4.481.

  PMID: 8707073 BACKGROUND

• Talley NJ, Fullerton S, Junghard O, Wiklund I. Quality of life in patients with endoscopy-negative heartburn: reliability and sensitivity of disease-specific instruments. Am J Gastroenterol. 2001 Jul;96(7):1998-2004. doi: 10.1111/j.1572-0241.2001.03932.x.

  PMID: 11467624 BACKGROUND

• Kulig M, Nocon M, Vieth M, Leodolter A, Jaspersen D, Labenz J, Meyer-Sabellek W, Stolte M, Lind T, Malfertheiner P, Willich SN. Risk factors of gastroesophageal reflux disease: methodology and first epidemiological results of the ProGERD study. J Clin Epidemiol. 2004 Jun;57(6):580-9. doi: 10.1016/j.jclinepi.2003.10.010.

  PMID: 15246126 BACKGROUND

• Kulig M, Leodolter A, Vieth M, Schulte E, Jaspersen D, Labenz J, Lind T, Meyer-Sabellek W, Malfertheiner P, Stolte M, Willich SN. Quality of life in relation to symptoms in patients with gastro-oesophageal reflux disease-- an analysis based on the ProGERD initiative. Aliment Pharmacol Ther. 2003 Oct 15;18(8):767-76. doi: 10.1046/j.1365-2036.2003.01770.x.

  PMID: 14535869 BACKGROUND

• Fass R, Ofman JJ. Gastroesophageal reflux disease--should we adopt a new conceptual framework? Am J Gastroenterol. 2002 Aug;97(8):1901-9. doi: 10.1111/j.1572-0241.2002.05912.x.

  PMID: 12190152 BACKGROUND

• Fass R. Erosive esophagitis and nonerosive reflux disease (NERD): comparison of epidemiologic, physiologic, and therapeutic characteristics. J Clin Gastroenterol. 2007 Feb;41(2):131-7. doi: 10.1097/01.mcg.0000225631.07039.6d.

  PMID: 17245209 BACKGROUND

• Carlsson R, Dent J, Watts R, Riley S, Sheikh R, Hatlebakk J, Haug K, de Groot G, van Oudvorst A, Dalvag A, Junghard O, Wiklund I. Gastro-oesophageal reflux disease in primary care: an international study of different treatment strategies with omeprazole. International GORD Study Group. Eur J Gastroenterol Hepatol. 1998 Feb;10(2):119-24.

  PMID: 9581986 BACKGROUND

• Venables TL, Newland RD, Patel AC, Hole J, Copeman MB, Turbitt ML. Maintenance treatment for gastro-oesophageal reflux disease. A placebo-controlled evaluation of 10 milligrams omeprazole once daily in general practice. Scand J Gastroenterol. 1997 Jul;32(7):627-32. doi: 10.3109/00365529708996509.

  PMID: 9246699 BACKGROUND

• Frazzoni M, De Micheli E, Savarino V. Different patterns of oesophageal acid exposure distinguish complicated reflux disease from either erosive reflux oesophagitis or non-erosive reflux disease. Aliment Pharmacol Ther. 2003 Dec;18(11-12):1091-8. doi: 10.1046/j.1365-2036.2003.01768.x.

  PMID: 14653828 BACKGROUND

• Dent J, Brun J, Fendrick A, Fennerty M, Janssens J, Kahrilas P, Lauritsen K, Reynolds J, Shaw M, Talley N. An evidence-based appraisal of reflux disease management--the Genval Workshop Report. Gut. 1999 Apr;44 Suppl 2(Suppl 2):S1-16. doi: 10.1136/gut.44.2008.s1. No abstract available.

  PMID: 10741335 BACKGROUND

• Dent J, Armstrong D, Delaney B, Moayyedi P, Talley NJ, Vakil N. Symptom evaluation in reflux disease: workshop background, processes, terminology, recommendations, and discussion outputs. Gut. 2004 May;53 Suppl 4(Suppl 4):iv1-24. doi: 10.1136/gut.2003.034272.

  PMID: 15082609 BACKGROUND

• Kahrilas PJ, Quigley EM. Clinical esophageal pH recording: a technical review for practice guideline development. Gastroenterology. 1996 Jun;110(6):1982-96. doi: 10.1053/gast.1996.1101982. No abstract available.

  PMID: 8964428 BACKGROUND

• Quigley EM. 24-h pH monitoring for gastroesophageal reflux disease: already standard but not yet gold? Am J Gastroenterol. 1992 Sep;87(9):1071-5. No abstract available.

  PMID: 1519562 BACKGROUND

• Pandolfino JE, Lee TJ, Schreiner MA, Zhang Q, Roth MP, Kahrilas PJ. Comparison of esophageal acid exposure at 1 cm and 6 cm above the squamocolumnar junction using the Bravo pH monitoring system. Dis Esophagus. 2006;19(3):177-82. doi: 10.1111/j.1442-2050.2006.00561.x.

  PMID: 16722995 BACKGROUND

• Pandolfino JE, Richter JE, Ours T, Guardino JM, Chapman J, Kahrilas PJ. Ambulatory esophageal pH monitoring using a wireless system. Am J Gastroenterol. 2003 Apr;98(4):740-9. doi: 10.1111/j.1572-0241.2003.07398.x.

  PMID: 12738450 BACKGROUND

• Hirano I, Richter JE; Practice Parameters Committee of the American College of Gastroenterology. ACG practice guidelines: esophageal reflux testing. Am J Gastroenterol. 2007 Mar;102(3):668-85. doi: 10.1111/j.1572-0241.2006.00936.x.

  PMID: 17335450 BACKGROUND

• Satoh K, Yamamoto H, Kawata H, Osawa H, Hanatsuka K, Kita H, Sunada K, Hirasawa T, Yoshizawa M, Ajibe H, Satoh Y, Sunada F, Sugano K. Comparison of hemostatic effects by route of H2 receptor antagonist administration following endoscopic mucosal resection in patients with neoplastic gastric lesions. Aliment Pharmacol Ther. 2005 Jun;21 Suppl 2:105-10. doi: 10.1111/j.1365-2036.2005.02483.x.

  PMID: 15943856 BACKGROUND

• Lundell LR, Dent J, Bennett JR, Blum AL, Armstrong D, Galmiche JP, Johnson F, Hongo M, Richter JE, Spechler SJ, Tytgat GN, Wallin L. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999 Aug;45(2):172-80. doi: 10.1136/gut.45.2.172.

  PMID: 10403727 BACKGROUND

• Amano Y, Ishimura N, Furuta K, Okita K, Masaharu M, Azumi T, Ose T, Koshino K, Ishihara S, Adachi K, Kinoshita Y. Interobserver agreement on classifying endoscopic diagnoses of nonerosive esophagitis. Endoscopy. 2006 Oct;38(10):1032-5. doi: 10.1055/s-2006-944778.

  PMID: 17058170 BACKGROUND

• Kiesslich R, Kanzler S, Vieth M, Moehler M, Neidig J, Thanka Nadar BJ, Schilling D, Burg J, Nafe B, Neurath MF, Galle PR. Minimal change esophagitis: prospective comparison of endoscopic and histological markers between patients with non-erosive reflux disease and normal controls using magnifying endoscopy. Dig Dis. 2004;22(2):221-7. doi: 10.1159/000080323.

  PMID: 15383765 BACKGROUND

• Yoshikawa I, Yamasaki M, Yamasaki T, Kume K, Otsuki M. Lugol chromoendoscopy as a diagnostic tool in so-called endoscopy-negative GERD. Gastrointest Endosc. 2005 Nov;62(5):698-703; quiz 752, 754. doi: 10.1016/j.gie.2005.06.027.

  PMID: 16246682 BACKGROUND

• Numans ME, Lau J, de Wit NJ, Bonis PA. Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics. Ann Intern Med. 2004 Apr 6;140(7):518-27. doi: 10.7326/0003-4819-140-7-200404060-00011.

  PMID: 15068979 BACKGROUND

• Dent J. Microscopic esophageal mucosal injury in nonerosive reflux disease. Clin Gastroenterol Hepatol. 2007 Jan;5(1):4-16. doi: 10.1016/j.cgh.2006.08.006. Epub 2006 Dec 8.

  PMID: 17157563 BACKGROUND

• Tobey NA, Carson JL, Alkiek RA, Orlando RC. Dilated intercellular spaces: a morphological feature of acid reflux--damaged human esophageal epithelium. Gastroenterology. 1996 Nov;111(5):1200-5. doi: 10.1053/gast.1996.v111.pm8898633.

  PMID: 8898633 BACKGROUND

• Zentilin P, Savarino V, Mastracci L, Spaggiari P, Dulbecco P, Ceppa P, Savarino E, Parodi A, Mansi C, Fiocca R. Reassessment of the diagnostic value of histology in patients with GERD, using multiple biopsy sites and an appropriate control group. Am J Gastroenterol. 2005 Oct;100(10):2299-306. doi: 10.1111/j.1572-0241.2005.50209.x.

  PMID: 16181384 BACKGROUND

• Gono K, Obi T, Yamaguchi M, Ohyama N, Machida H, Sano Y, Yoshida S, Hamamoto Y, Endo T. Appearance of enhanced tissue features in narrow-band endoscopic imaging. J Biomed Opt. 2004 May-Jun;9(3):568-77. doi: 10.1117/1.1695563.

  PMID: 15189095 BACKGROUND

• Kumagai Y, Inoue H, Nagai K, Kawano T, Iwai T. Magnifying endoscopy, stereoscopic microscopy, and the microvascular architecture of superficial esophageal carcinoma. Endoscopy. 2002 May;34(5):369-75. doi: 10.1055/s-2002-25285.

  PMID: 11972267 BACKGROUND

• el-Serag HB, Sonnenberg A. Associations between different forms of gastro-oesophageal reflux disease. Gut. 1997 Nov;41(5):594-9. doi: 10.1136/gut.41.5.594.

  PMID: 9414963 BACKGROUND

• Sharma P, Bansal A, Mathur S, Wani S, Cherian R, McGregor D, Higbee A, Hall S, Weston A. The utility of a novel narrow band imaging endoscopy system in patients with Barrett's esophagus. Gastrointest Endosc. 2006 Aug;64(2):167-75. doi: 10.1016/j.gie.2005.10.044.

  PMID: 16860063 BACKGROUND

• Abstracts of Digestive Disease Week, May 17-22, 2008 and the ASGE (American Society for Gastrointestinal Endoscopy) Postgraduate Course, May 21-22, 2008. San Diego, California, USA. Gastrointest Endosc. 2008 Apr;67(5):AB57-349. No abstract available.

  PMID: 18578045 BACKGROUND

• 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

• Locke GR 3rd, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Risk factors associated with symptoms of gastroesophageal reflux. Am J Med. 1999 Jun;106(6):642-9. doi: 10.1016/s0002-9343(99)00121-7.

  PMID: 10378622 BACKGROUND

• Locke GR, Talley NJ, Weaver AL, Zinsmeister AR. A new questionnaire for gastroesophageal reflux disease. Mayo Clin Proc. 1994 Jun;69(6):539-47. doi: 10.1016/s0025-6196(12)62245-9.

  PMID: 8189759 BACKGROUND

• Shaw MJ, Talley NJ, Beebe TJ, Rockwood T, Carlsson R, Adlis S, Fendrick AM, Jones R, Dent J, Bytzer P. Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease. Am J Gastroenterol. 2001 Jan;96(1):52-7. doi: 10.1111/j.1572-0241.2001.03451.x.

  PMID: 11197287 BACKGROUND

• Fock KM, Teo EK, Ang TL, Tan JY, Law NM. The utility of narrow band imaging in improving the endoscopic diagnosis of gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2009 Jan;7(1):54-9. doi: 10.1016/j.cgh.2008.08.030. Epub 2008 Sep 3.

  PMID: 18852068 BACKGROUND

• Desai M, Srinivasan S, Sundaram S, Dasari C, Andraws N, Mathur S, Higbee A, Miller J, Beg S, Fateen W, Sami SS, Repici A, Ragunath K, Sharma P. Narrow-band imaging for the diagnosis of nonerosive reflux disease: an international, multicenter, randomized controlled trial. Gastrointest Endosc. 2022 Sep;96(3):457-466.e3. doi: 10.1016/j.gie.2022.04.020. Epub 2022 Apr 26.

  PMID: 35487299 DERIVED

MeSH Terms

Conditions

Non-Erosive Reflux Disease

Interventions

Esomeprazole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Omeprazole; 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

• Prateek Sharma, M.D.

  VA Office of Research and Development

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator,

Study Record Dates

• First Submitted: April 6, 2012
• First Posted: March 7, 2014
• Study Start: March 1, 2009
• Primary Completion: January 5, 2020
• Study Completion: August 5, 2020
• Last Updated: March 16, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1); GB (1)