Nociceptors, Neurotrophic Factors and Cytokine Expression in Gastroesophageal Reflux Disease

Symptomatic Gastroesophageal Reflux Disease is Associated With Increased TRPV1 and PAR2 mRNA Expression Levels in the Esophageal Mucosa

Transient receptor potential vanilloid-1 (TRPV1) receptor and proteinase-activated receptor 2 (PAR2) have been implicated in the mechanism of acid induced inflammation in gastroesophageal reflux disease (GERD). We aimed to evaluate TRPV1 and PAR2 mRNA expression levels in the GERD patients and their relationship with endoscopic findings and reflux symptoms.

Study Overview

• Status: Completed
• Conditions: Gastro-esophageal Reflux Disease
• Intervention / Treatment: Procedure: endoscopic mucosal biopsy

Detailed Description

All the subjects receive upper GI endoscopy and completed questionnaires about GERD symptoms under the supervision of a well-trained interviewer. Subjects are excluded if there was a history of gastrointestinal surgery, Barrett's esophagus, esophageal motility disorder, duodenal ulcer, benign gastric ulcer or gastroduodenal cancer and if he or she had any history of systemic disease requiring chronic medication (except for hypertension and diabetes mellitus).

The subjects are classified into 3 groups after upper GI endoscopy and completing questionnaires about GERDsymptoms ; ERD(erosive reflux disease), NERD(nonerosive reflux disease) and control group.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Seongnam, Gyeonggi-do, Korea, Republic of
      • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• subjects who completed upper GI endoscopy and questionnaires about GERD symptoms

Exclusion Criteria:

• a history of gastrointestinal surgery
• Barrett's esophagus
• esophageal motility disorder
• duodenal ulcer
• benign gastric ulcer
• gastroduodenal cancer
• if he or she had any history of systemic disease requiring chronic medication (except for hypertension and diabetes mellitus).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
SHAM_COMPARATOR: control group; Subjects who do not show mucosal breaks in the upper GI endoscopy consistent with reflux esophagitis and do not complain of GERD symptoms. Endoscopic mucosal biopsy was done for every subject.	Procedure: endoscopic mucosal biopsy; endoscopic mucosal biopsy was undertaken for every participant.
ACTIVE_COMPARATOR: ERD group; Subjects who have mucosal breaks in the upper GI endoscopy consistent with reflux esophagitis and/or complain of GERD symptoms. Endoscopic mucosal biopsy was done for every subject.	Procedure: endoscopic mucosal biopsy; endoscopic mucosal biopsy was undertaken for every participant.
ACTIVE_COMPARATOR: NERD group; Subjects who do not have mucosal breaks in the upper GI endoscopy consistent with reflux esophagitis and complain of GERD symptoms. Endoscopic mucosal biopsy was done for every subject.	Procedure: endoscopic mucosal biopsy; endoscopic mucosal biopsy was undertaken for every participant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TRPV1, GDNF, and NGF mRNA Expression of Esophageal Mucosa	The primers used in real-time qPCR were designed using PrimerExpress Software V2.0 (Applied Biosystems, Foster City, CA, USA) based on sequence information from the National Center for Biotechnology Information database. Real-time qPCR was performed in triplicate by using a StepOnePlus Real-time PCR (Applied Biosystems) with SYBR Premix Ex TaqTM (Takara Bio, Shiga, Japan) according to manufacturers' instructions and protocols. Thermal cycling was performed as follows: initial denaturation at 95 °C for 10s followed by 40 cycles of 95 °C for 5 s and 60 °C for 33s. Homo b-actin was used as a reference; i.e. each sample was normalized on the basis of its b-actin content. The relative change in all target genes expression was determined by the fold-change analysis.	up to 24weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PAR2 and IL-8 Expression of Esophageal Mucosa	The primers used in real-time qPCR were designed using PrimerExpress Software V2.0 (Applied Biosystems, Foster City, CA, USA) based on sequence information from the National Center for Biotechnology Information database. Real-time qPCR was performed in triplicate by using a StepOnePlus Real-time PCR (Applied Biosystems) with SYBR Premix Ex TaqTM (Takara Bio, Shiga, Japan) according to manufacturers' instructions and protocols. Thermal cycling was performed as follows: initial denaturation at 95 °C for 10s followed by 40 cycles of 95 °C for 5 s and 60 °C for 33s. Homo b-actin was used as a reference; i.e. each sample was normalized on the basis of its b-actin content. The relative change in all target genes expression was determined by the fold-change analysis.	up to 24weeks

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Investigators: Principal Investigator: Nayoung Kim, M.D., Professor

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (ACTUAL): August 1, 2014
• Study Completion (ACTUAL): August 1, 2014

Study Registration Dates

• First Submitted: March 23, 2014
• First Submitted That Met QC Criteria: April 11, 2014
• First Posted (ESTIMATE): April 15, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): May 2, 2016
• Last Update Submitted That Met QC Criteria: April 24, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux
• Other Study ID Numbers: B-1211/180-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED