Detection of Minimal Change Esophagitis Using Confocal Laser Endomicroscopy - Full Text View

Sponsored by:	National University Hospital, Singapore
Information provided by:	National University Hospital, Singapore
ClinicalTrials.gov Identifier:	NCT00954070

Purpose

This is an observational, prospective and pilot study to determine through confocal endomicroscopy diagnostic microscopic features detectable at the gastroesophageal junction of patients with non-erosive gastroesophageal reflux disease.

The hypothesis is that minimal mucosal changes occur in non-erosive gastroesophageal reflux disease. Although these minimal changes are not always visible on white-light endoscopy, it is detectable using high-resolution confocal endomicroscopy and these confocal features are diagnostic of non-erosive reflux disease (NERD).

Condition	Intervention
Non-Erosive Gastroesophageal Reflux Disease	Device: Confocal endomicroscope (Pentax Model EC3870K)

Study Type:	Observational
Study Design:	Case Control, Prospective
Official Title:	Detection of Minimal Change Esophagitis Using Confocal Laser Endomicroscopy

Resource links provided by NLM:

MedlinePlus related topics: GERD

U.S. FDA Resources

Further study details as provided by National University Hospital, Singapore:

Primary Outcome Measures:

Specific microscopic changes in the esophageal mucosa as seen under the confocal endomicroscope [ Time Frame: After 4 weeks phamacological washout period ] [ Designated as safety issue: No ]

Biospecimen Retention: None Retained

Biospecimen Description:

Estimated Enrollment:	120
Study Start Date:	June 2009
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Case (subjects with NERD) The investigators cases are subjects with confirmed NERD and include male or female patients aged between 21 and 65 years, who present with typical clinical manifestations of gastroesophageal reflux and have no esophageal mucosal breaks upon conventional white-light endoscopy examination but show evidence of pathologic gastroesophageal reflux on 24-hr pH monitoring.	Device: Confocal endomicroscope (Pentax Model EC3870K) The intervention is an endoscopy procedure using a novel type of endoscope with a powerful confocal microscope attached to its tip. The endoscope (Pentax Model EC3870K) provides both white-light and confocal microscopic imaging.
Control Healthy individuals aged between 21 and 65 years who are asymptomatic for GERD and other digestive diseases	Device: Confocal endomicroscope (Pentax Model EC3870K) The intervention is an endoscopy procedure using a novel type of endoscope with a powerful confocal microscope attached to its tip. The endoscope (Pentax Model EC3870K) provides both white-light and confocal microscopic imaging.

Detailed Description:

In Asia, up to 70% of patients with typical gastroesophageal reflux symptoms could have non-erosive reflux disease (NERD), in which case, no detectable mucosal break may be observed on conventional white-light endoscopy.

However, minimal change lesions are often visible upon high-resolution endoscopy and on microscopic examination of biopsied specimens. The most commonly seen microscopic features are dilated intercellular space, infiltration of inflammatory cells into squamous epithelia, hyperplasia of the epithelial basal cell and elongation of the papillae. So far, the most consistent histologic change found in NERD has been the dilated intercellular space in esophageal epithelium. But until now, determinations of intercellular space dilatations could only be done ex-vivo on biopsy specimens using transmission electron microscopy or light microscopy. With the advent of high-resolution confocal laser endomicroscopy, in-vivo determination of intercellular space dilatations and other diagnostic microscopic features could be a reality. This study is aimed at exploring such a clinical possibility and feasibility, with the intention of comparing the microscopic findings based on confocal endomicroscopy with that of symptoms, and esophageal pH.

Eligibility

Ages Eligible for Study:	21 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Hosipital patients with typical clinical manifestations of gastroesophageal reflux disease but no endoscopy evidence of esophagitis.

Criteria

Inclusion Criteria:

Cases:
- male or female patients aged between 21 and 65 years with typical clinical manifestations of gastroesophageal reflux but endoscopy-negative for esophageal mucosal breaks
- by typical clinical manifestations of gastroesophageal reflux, we refer to the occurrence of heartburn and/or regurgitation more than twice a week, with a minimum duration of 8 consecutive weeks, and with symptoms severe enough to affect daily activities
Controls:
- healthy male or female aged between 21 and 65 years who are asymptomatic for GERD and other digestive diseases

Exclusion Criteria:

Endoscopic confirmed erosive esophagitis
Complications such as Barrett's esophagus, gastric and/or duodenal peptic ulcer, stenosis
Esophageal, gastric or duodenal cancer or other malignancy
History of esophagus, stomach, or duodenum surgery
Conditions that preclude safe biopsies (coagulopathy, haemophilia, esophageal varices, and patients on warfarin and antiplatelets)
Scleroderma, diabetes mellitus, autonomic or peripheral neuropathy, myopathy or any underlying disease or medication that might affect the lower esophageal sphincter pressure or increase the acid clearance time
A history of bronchial asthma, or known allergy to fluorescein
Pregnant or breast-feeding (for females)
Below 21 or above 65 years of age
Severe co-morbidities (e.g., such as end-stage renal failure, congestive cardiac failure, liver cirrhosis, severe arthritis requiring long term non-steroidal anti-inflammatory drug therapy)
Unable or unwilling to give informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00954070

Contacts

Contact: Khek Yu Ho, MD

65-67724362

mdchoky@nus.edu.sg

Locations

Singapore
National University Hospital	Recruiting
Singapore, Singapore, 119074
Contact: Angela LP Yeo 65-67722643 mdcylp@nus.edu.sg
Principal Investigator: Khek Yu Ho, MD
Sub-Investigator: KG Yeoh, MMed
Sub-Investigator: Lee Guan Lim, MBBS, MRCP
Sub-Investigator: Manuel Salto-Tellez, MD
Sub-Investigator: Ting Ting Wang, MD
Sub-Investigator: Supriya Srivastava, MD Pathology

Sponsors and Collaborators

National University Hospital, Singapore

Investigators

Principal Investigator:

Khek Yu Ho, MD

National University Hospital, Singapore

More Information

Publications:

Barlow WJ, Orlando RC. The pathogenesis of heartburn in nonerosive reflux disease: a unifying hypothesis. Gastroenterology. 2005 Mar;128(3):771-8. Review.

Calabrese C, Fabbri A, Bortolotti M, Cenacchi G, Areni A, Scialpi C, Miglioli M, Di Febo G. Dilated intercellular spaces as a marker of oesophageal damage: comparative results in gastro-oesophageal reflux disease with or without bile reflux. Aliment Pharmacol Ther. 2003 Sep 1;18(5):525-32.

Ravelli AM, Villanacci V, Ruzzenenti N, Grigolato P, Tobanelli P, Klersy C, Rindi G. Dilated intercellular spaces: a major morphological feature of esophagitis. J Pediatr Gastroenterol Nutr. 2006 May;42(5):510-5.

Caviglia R, Ribolsi M, Gentile M, Rabitti C, Emerenziani S, Guarino MP, Petitti T, Cicala M. Dilated intercellular spaces and acid reflux at the distal and proximal oesophagus in patients with non-erosive gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2007 Mar 1;25(5):629-36.

Caviglia R, Ribolsi M, Maggiano N, Gabbrielli AM, Emerenziani S, Guarino MP, Carotti S, Habib FI, Rabitti C, Cicala M. Dilated intercellular spaces of esophageal epithelium in nonerosive reflux disease patients with physiological esophageal acid exposure. Am J Gastroenterol. 2005 Mar;100(3):543-8.

Responsible Party:	National University Hospital ( Professor Ho Khek Yu )
Study ID Numbers:	E/09/026
Study First Received:	July 8, 2009
Last Updated:	August 5, 2009
ClinicalTrials.gov Identifier:	NCT00954070 History of Changes
Health Authority:	Singapore: Domain Specific Review Boards

Keywords provided by National University Hospital, Singapore:

gastroesophageal reflux disease

Study placed in the following topic categories:

Deglutition Disorders
Esophageal Motility Disorders
Esophagitis
Digestive System Diseases
Esophageal Disorder

Gastrointestinal Diseases
Esophageal Diseases
Gastroenteritis
Gastroesophageal Reflux

Additional relevant MeSH terms:

Deglutition Disorders
Esophageal Motility Disorders
Esophagitis
Digestive System Diseases

Gastrointestinal Diseases
Esophageal Diseases
Gastroenteritis
Gastroesophageal Reflux

ClinicalTrials.gov processed this record on September 11, 2009