Clinical trial NCT00954070: Detection of Minimal Change Esophagitis Using Confocal Laser Endomicroscopy
Official title: Detection of Minimal Change Esophagitis Using Confocal Laser Endomicroscopy
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Gastroesophageal Reflux Disease
Keywords: gastroesophageal reflux disease
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
First posted: 2009-08-06
Enrollment: 6
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hosipital patients with typical clinical manifestations of gastroesophageal reflux disease but no endoscopy evidence of esophagitis.

Brief summary: 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).

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 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

Primary outcomes:
measure: Specific microscopic changes in the esophageal mucosa as seen under the confocal endomicroscope
timeFrame: After 4 weeks phamacological washout period
Secondary outcomes:
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: National University Hospital, Singapore
name: Khek Yu Ho, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barlow WJ, Orlando RC. The pathogenesis of heartburn in nonerosive reflux disease: a unifying hypothesis. Gastroenterology. 2005 Mar;128(3):771-8. doi: 10.1053/j.gastro.2004.08.014.
citation: 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. doi: 10.1046/j.1365-2036.2003.01713.x.
citation: 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. doi: 10.1097/01.mpg.0000215312.78664.b9.
citation: 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. doi: 10.1111/j.1365-2036.2006.03237.x.
citation: 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. doi: 10.1111/j.1572-0241.2005.40978.x.