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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastro-esophageal Reflux Disease
• Intervention / Treatment: Procedure: Upper gastrointestinal (GI) endoscopy; Procedure: Wireless pH monitoring; Procedure: Post prandial esophageal High Resolution Impedance Manometry; Procedure: pH-impedance monitoring

• Study Type: Interventional
• Enrollment (Estimated): 330
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sabine ROMAN, MD; Phone Number: +33 4 72 11 01 36; Email: sabine.roman@chu-lyon.fr

Study Locations

• France
  • Chambray-lès-Tours, France, 37171
    • Recruiting
    • Service d'Hepato-Gastroenterologie - Hôpital Trousseau - CHU de Tours
    • Contact: Alexandre AUBOURG, MD
    • Principal Investigator: Alexandre AUBOURG, MD
  • Colombes, France, 92700
    • Recruiting
    • Service d'Hepato-Gastroenterologie - Hôpital Louis Mourier - APHP
    • Contact: Benoit COFFIN, MD
    • Principal Investigator: Benoit COFFIN, MD
  • Lyon, France, 69437
    • Recruiting
    • Service d'Explorations Fonctionnelles Digestives - Hôpital Edouard Herriot - HCL
    • Contact: Sabine ROMAN, MD
    • Principal Investigator: Sabine ROMAN, MD
  • Nantes, France, 44093
    • Recruiting
    • Service d'Hepato-Gastroenterologie - Hôtel Dieu - CHU de Nantes
    • Contact: Stanislas BRULEY DES VARANNES, MD
    • Principal Investigator: Stanislas BRULEY DES VARANNES, MD
  • Pessac, France, 33600
    • Recruiting
    • Service d'Hepato-Gastroenterologie - Hôpital Haut Lévêque - CHU de Bordeaux
    • Contact: Frank ZERBIB, MD
    • Principal Investigator: Frank ZERBIB, MD
  • Rennes, France, 35033
    • Recruiting
    • Service d'Hepato-Gastroenterologie - Hôpital Pontchaillou- CHU de Rennes
    • Contact: Alain ROPERT, MD
    • Principal Investigator: Alain ROPERT, MD
  • Rouen, France, 76031
    • Recruiting
    • Service de Physiologie Digestive, Respiratoire, Urinaire et Sportive - CHU de Rouen
    • Contact: Guillaume GOURCEROL, MD
    • Principal Investigator: Guillaume GOURCEROL, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with persistent GERD; Patients with persistent GERD suggestive symptoms despite PPI therapy. All the patients will undergo an upper gastrointestinal (GI) endoscopy, a wireless pH monitoring and a post prandial esophageal High Resolution Impedance Manometry (HRIM). Optional: 24-h pH-impedance monitoring on PPI

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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of reflux episodes identified on the post prandial HRIM	The diagnostic performance of the number of reflux episodes measured by 1-hour post prandial HRIM will be evaluated by estimating the Area Under the ROC Curve and its 95% confidence interval. The gold standard to define GERD will be based on esophageal pH measurements with capsule (GERD is defined as acid exposure time (AET; percentage of total time with esophageal pH < 4) greater than 6% for at least one day on wireless pH monitoring).	1 hour after the end of the meal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acid exposure time measured on wireless pH-monitoring	The diagnosis of GERD based on pH-monitoring. The diagnosis of GERD is positive if acid exposure time (AET; percentage of total time with esophageal pH < 4) is greater than 6% for at least one day on wireless pH monitoring. The diagnosis of GERD is negative (ie absence of GERD) if the AET is below 4% during the 4 days of wireless monitoring. In the other instance , the diagnosis of GERD is uncertain.	4 days
Reflux mechanisms defined on post prandial HRIM	Description of the reflux mechanisms associated with reflux episodes: rumination, transient lower esophageal sphincter relaxation (TLESR), defective esophago-gastric junction (EGJ) or unknown.	1 hour after the end of the meal
Baseline impedance measured on post prandial HRIM	Measure of baseline impedance on a period without swallow 3 and 5 cm above the proximal border of the esophago-gastric junction	1 hour after the end of the meal
Resting pressure of the esophago-gastric junction	Measure of the resting pressure of the esophago-gastric junction on a period without swallowing	1 hour
Esophageal histology	Presence of eosinophils cells in the esophageal mucosa > 15/hpf, dilated intercellular spaces, and/or papillar elongation	4 weeks
Response to 4-week regimen of dose PPI	Clinical response is defined as a Reflux Disease Questionnaire score on PPI ≤ 3 after 4-week treatment	4 weeks
Normalization of the number of reflux episodes detected on 24-h pH-impedance monitoring performed on PPI	The number of reflux episodes is normalized if the total number of reflux episodes is < 60 /24 h) on pH-impedance monitoring performed on PPI.	1 day
Normalization of the acid exposure time measured on 24-h pH-impedance monitoring performed on PPI	The esophageal acid exposure (AET) is normalized if it is below 4% on pH-impedance monitoring performed on PPI.	1 day
Patient's preference regarding the type of examination	Percentage of patients who preferred the wireless pH capsule and percentage of patients who preferred HRIM.	1 day

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2021
• Primary Completion (Estimated): May 3, 2027
• Study Completion (Estimated): May 3, 2027

Study Registration Dates

• First Submitted: July 11, 2018
• First Submitted That Met QC Criteria: July 11, 2018
• First Posted (Actual): July 23, 2018

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Gastro-esophageal reflux; High resolution Impedance Manometry; Resistance to proton pump inhibitors (PPI)
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Intestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Esophagitis; Peptic Ulcer; Duodenal Diseases; Gastroesophageal Reflux; Esophagitis, Peptic
• Other Study ID Numbers: 69HCL18_0043; 2018-A01591-54 (Other Identifier: ID-RCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No