Gastro-esophageal Reflux Disease
Conditions
Brief summary
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.
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.
Interventions
PROCEDUREendoscopic mucosal biopsy
endoscopic mucosal biopsy was undertaken for every participant.
Sponsors
Seoul National University Bundang Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TRPV1, GDNF, and NGF mRNA Expression of Esophageal Mucosa | up to 24weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PAR2 and IL-8 Expression of Esophageal Mucosa | up to 24weeks | 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. |
Countries
South Korea
Participant flow
Recruitment details
The subjects were enrolled prospectively at Seoul National University Bundang Hospital between March 2010 and August 2014. Those enrolled subjects visited SNUBH gastroenterology department mainly for evaluating the origin of suspicious GERD symptoms or for screening of gastric cancer.
Pre-assignment details
Subjects were excluded if there was a history of gastrointestinal surgery, Barrett's esophagus, esophageal motility disorder, duodenal ulcer, benign gastric ulcer or gastroduodenal cancer and any history of systemic disease requiring chronic medication (except for hypertension and diabetes mellitus).
Participants by arm
| Arm | Count |
|---|---|
| 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 | 16 |
| ERD Group subjects who have mucosal breaks in the upper GI endoscopy consistent with reflux esophagitis and/or complain of GERD symptoms | 45 |
| NERD Group subjects who do not have mucosal breaks in the upper GI endoscopy consistent with reflux esophagitis and complain of GERD symptoms | 14 |
| Total | 75 |
Baseline characteristics
| Characteristic | Control Group | ERD Group | NERD Group | Total |
|---|---|---|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 11.6 | 52.3 years STANDARD_DEVIATION 10.39 | 52.7 years STANDARD_DEVIATION 13.8 | 52.8 years STANDARD_DEVIATION 12.1 |
| Sex: Female, Male Female | 9 Participants | 22 Participants | 7 Participants | 38 Participants |
| Sex: Female, Male Male | 7 Participants | 23 Participants | 7 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
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.
Time frame: up to 24weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | TRPV1, GDNF, and NGF mRNA Expression of Esophageal Mucosa | GDNF | 1.39 Fold change | Standard Error 0.35 |
| Control Group | TRPV1, GDNF, and NGF mRNA Expression of Esophageal Mucosa | TRPV1 | 1.14 Fold change | Standard Error 0.25 |
| Control Group | TRPV1, GDNF, and NGF mRNA Expression of Esophageal Mucosa | NGF | 1.62 Fold change | Standard Error 0.37 |
| ERD Group | TRPV1, GDNF, and NGF mRNA Expression of Esophageal Mucosa | GDNF | 2.47 Fold change | Standard Error 0.33 |
| ERD Group | TRPV1, GDNF, and NGF mRNA Expression of Esophageal Mucosa | TRPV1 | 3.25 Fold change | Standard Error 0.32 |
| ERD Group | TRPV1, GDNF, and NGF mRNA Expression of Esophageal Mucosa | NGF | 2.65 Fold change | Standard Error 0.21 |
| NERD Group | TRPV1, GDNF, and NGF mRNA Expression of Esophageal Mucosa | TRPV1 | 2.33 Fold change | Standard Error 0.22 |
| NERD Group | TRPV1, GDNF, and NGF mRNA Expression of Esophageal Mucosa | NGF | 2.29 Fold change | Standard Error 0.13 |
| NERD Group | TRPV1, GDNF, and NGF mRNA Expression of Esophageal Mucosa | GDNF | 2.05 Fold change | Standard Error 0.16 |
Secondary
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.
Time frame: up to 24weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | PAR2 and IL-8 Expression of Esophageal Mucosa | PAR2 | 1.37 Fold change | Standard Error 0.2 |
| Control Group | PAR2 and IL-8 Expression of Esophageal Mucosa | IL8 | 2.01 Fold change | Standard Error 0.6 |
| ERD Group | PAR2 and IL-8 Expression of Esophageal Mucosa | PAR2 | 2.42 Fold change | Standard Error 0.17 |
| ERD Group | PAR2 and IL-8 Expression of Esophageal Mucosa | IL8 | 4.36 Fold change | Standard Error 0.32 |
| NERD Group | PAR2 and IL-8 Expression of Esophageal Mucosa | PAR2 | 2.29 Fold change | Standard Error 0.36 |
| NERD Group | PAR2 and IL-8 Expression of Esophageal Mucosa | IL8 | 4.01 Fold change | Standard Error 0.35 |