Diagnostic Yield of Post PRandial Esophageal High Resolution Impedance Manometry in Patients With Gastro-Esophageal Reflux Disease Symptoms Resistant to Proton Pump Inhibitor Therapy

Overview

Gastro-esophageal reflux disease (GERD) is defined as the reflux of gastric content into the esophagus that causes troublesome symptoms or complications. Nine to 30% of the population suffers from GERD-suggestive symptoms (heartburn, regurgitation, chest pain, chronic couch, sore throat). In the absence of warning signs, proton pump inhibitors (PPI) are prescribed as first-line treatment. However, 20 to 60% of patients are unsatisfied because of persistent symptoms when taking PPI. Causes of persistent symptoms are: erroneous diagnosis of GERD (up to 50% of PPI non-responders), rumination syndrome, excessive weakly acid reflux on PPI due to defective esophago-gastric junction or an excessive number of transient lower esophageal sphincter relaxations (main mechanism of GERD), poor acid secretion inhibition on PPI, and non-compliance to therapy. Complementary examinations are indicated to explain persistent GERD symptoms. Upper gastro-intestinal endoscopy is performed first to rule out an esophageal tumor and to identify erosive esophagitis, a specific sign of GERD. However, it is normal in up to 70% of symptomatic GERD patients. Direct detection of reflux episodes is then requested to confirm GERD. The gold standard for reflux detection is the ambulatory measurement of esophageal pH for 24 to 96 hours using a catheter (catheter-based pH-monitoring) or a capsule clipped into the esophagus (wireless pH-monitoring). Reflux episodes are defined as an esophageal pH \< 4. Another method of reflux detection is based on liquid and gas detection in the esophagus using pH-impedance monitoring. Recently the combination of impedance and esophageal pressure monitoring, called esophageal high resolution impedance manometry (HRIM) was introduced to simultaneously identify reflux episodes and their mechanisms. It has several advantages over esophageal pH measurement: shorter recording duration (1 or 2 hours post prandial) and identification of reflux mechanisms that might guide the choice of the best therapeutic option. Hypothesis: The 1-hour post prandial esophageal HRIM might be useful to diagnose GERD.

Interventions

• Procedure Upper gastrointestinal (GI) endoscopy
  An upper gastrointestinal (GI) endoscopy will be performed at V1. Four esophageal biopsies will be taken in both the proximal and the distal esophagus.
• Procedure Wireless pH monitoring
  Wireless pH monitoring will be performed at V1. The pH capsule will be clipped into the esophagus during the upper GI endoscopy. The esophageal pH will be recorded for 96 hours (ambulatory recording).
• Procedure Post prandial esophageal High Resolution Impedance Manometry
  Post prandial esophageal HRIM will be performed at V2. The recording will be started after transnasal insertion of the HRIM probe. A standardized meal will be given to the patient (Big Mac, medium portion of French fries, orange juice). The recording will be realized for one hour after the end of the meal.
• Procedure pH-impedance monitoring
  24-h pH-impedance monitoring on PPI will be performed at V3. A transnasal catheter will be inserted into the esophagus and the recording will be performed for 24 hours (ambulatory recording).

Primary outcome measures

• Number of reflux episodes identified on the post prandial HRIM [Time frame: 1 hour after the end of the meal]

Secondary outcome measures (9)

• Acid exposure time measured on wireless pH-monitoring [Time frame: 4 days]
• Reflux mechanisms defined on post prandial HRIM [Time frame: 1 hour after the end of the meal]
• Baseline impedance measured on post prandial HRIM [Time frame: 1 hour after the end of the meal]
• Resting pressure of the esophago-gastric junction [Time frame: 1 hour]
• Esophageal histology [Time frame: 4 weeks]
• Response to 4-week regimen of dose PPI [Time frame: 4 weeks]
• Normalization of the number of reflux episodes detected on 24-h pH-impedance monitoring performed on PPI [Time frame: 1 day]
• Normalization of the acid exposure time measured on 24-h pH-impedance monitoring performed on PPI [Time frame: 1 day]
• Patient's preference regarding the type of examination [Time frame: 1 day]

Eligibility criteria

Inclusion criteria

• Patient older than 18 years
• Typical symptoms of GERD (heartburn, regurgitation) at least twice a week despite PPI therapy for at least one month.
• Reflux Disease Questionnaire (RDQ) score off PPI > 3
• Subject with health insurance

Exclusion criteria

• Previous esophago-gastric surgery,
• Previous history of developing esophageal or gastric tumor, esophageal stricture, or esophageal varices
• Pregnancy (assessment at V0)
• Contraindication to general anesthesia,
• Contraindications to the wireless capsule pH-monitoring: pacemakers, implantable cardiac defibrillator,
• Contraindications to HRIM: inability to tolerate nasal intubation, significant bleeding disorders for which nasal intubation is contraindicated, known esophageal obstruction is preventing the passage of the HRIM probe.
• Intolerance or allergy to one component of the test meal,
• Intolerance or allergy to PPI,
• Inability to give consent,
• Mentally unbalanced patients, under supervision or guardianship
• Decline to participate in the study,
• Participation in another study at the same time

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

France · 7 centers

• Service d'Hepato-Gastroenterologie - Hôpital Trousseau - CHU de Tours — Chambray-lès-Tours
• Service d'Hepato-Gastroenterologie - Hôpital Louis Mourier - APHP — Colombes
• Service d'Explorations Fonctionnelles Digestives - Hôpital Edouard Herriot - HCL — Lyon
• Service d'Hepato-Gastroenterologie - Hôtel Dieu - CHU de Nantes — Nantes
• Service d'Hepato-Gastroenterologie - Hôpital Haut Lévêque - CHU de Bordeaux — Pessac
• Service d'Hepato-Gastroenterologie - Hôpital Pontchaillou- CHU de Rennes — Rennes
• Service de Physiologie Digestive, Respiratoire, Urinaire et Sportive - CHU de Rouen — Rouen

Identifiers

NCT: NCT03596476 · 69HCL18_0043 · 2018-A01591-54

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗