Thresholds of Straight Leg Raise Maneuver During High-Resolution-Manometry

Study Overview
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Brief Summary
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High resolution manometry (HRM) is a key test in the preoperative assessment of patients with gastro-esophageal reflux disease (GERD) who are potential candidates for antireflux surgery. The recent Lyon consensus suggested the potential usefulness of HRM in diagnosing GERD, however, sensitivity and specificity of HRM for GERD remains low (53.6% and 72.5% respectively). Among recently proposed provocative tests during manometry, a traditional maneuver (straight leg raise maneuver, SLR) appeared promising in predicting reflux. This is a multicenter study involving high-volume esophageal function laboratories around the world. Patients with suspected GERD and tested with HRM and pH-impedance will be asked to perform SLR during HRM. Intra-abdominal and intra-esophageal pressure during SLR will be recorded and compared with acid exposure time (AET) at pH-impedance. Primary aim is to determine the optimal threshold of intra-esophageal pressure augmentation during straight leg raise (SLR) maneuver that predicts pathological esophageal acid exposure time (AET). Secondary aim is to assess the diagnostic performance of HMR with SRL maneuver, calculating sensitivity, specificity, false-positive rate (FPR), false-negative rate (FNR), positive predictive value and total misclassification rate.

Detailed Description
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It has been demonstrated a low sensitivity and specificity of HRM for GERD (53.6% and 72.5% respectively), since there was a significant overlap between patients and controls in the majority of parameters. Masuda et al. attempted to improve HRM accuracy using a comprehensive index and new parameters, such as the backflow preventive and promotive pressure through the lower esophageal sphincter (LES). Although a significant correlation between reflux burden and the new index was found, sensitivity and specificity of HRM for GERD remained unchanged. Recently, provocative tests have been added to the standard protocol of HRM studies. Among these, a traditional maneuver in water perfused manometry (straight leg raise maneuver, SLR) appeared promising in predicting reflux even with HRM. A multicenter study with a large number of patients could provide more precise thresholds to predict pathologic esophageal acid exposure time and proof of real-life generalizability of SLR. A thorough clinical evaluation will be performed. GerdQ, GERD Health Related Quality of Life (GERD-HRQL) and Reflux Symptom Index (RSI) questionnaires will be administered. HRM will be performed according to the standard protocol defined by Chicago Classification 4.0. Upon completion of the test, the SLR maneuver will be performed. With the patient in supine position, one leg is raised to form an angle of at least 45 degrees with the bed. The patient will be asked to keep that position for at least 5 seconds. The maneuver will be repeated after 20-30 seconds. The first adequate maneuver will be considered for the study. Intra-esophageal and intra-abdominal pressure will be analyzed both during baseline and SLR maneuver. Intra-esophageal pressure is measured as peak and mean over 5 seconds, 1 cm and 5 cm above the proximal margin of the LES. Intra-abdominal pressure will be measured as peak and mean over 5 seconds 1 cm below the distal margin of the diaphragm notch. Primary aim is to determine the optimal threshold of intra-esophageal pressure augmentation during straight leg raise (SLR) maneuver that predicted pathological esophageal acid exposure time (AET). Secondary aim is to assess the diagnostic performance of HMR with SRL maneuver in patients with GERD symptoms, calculating sensitivity, specificity, false-positive rate (FPR), false-negative rate (FNR) and total misclassification rate. The Principal Investigator will maintain research data on an encrypted file server with access controls only accessible to approved study investigators. Research records will be de-identified using coded subject identifiers prior to transfer from sites to the Principal Investigator to protect patient confidentiality. Study data will be maintained by the Principal Investigator and deleted 3 years after the end of the study. Data from each site will be electronically transferred to Principal Investigator. The electronic copy will contain no patient identifying data elements such as name, date of birth, medical record numbers. Participating institutions will create unique patient participant numbers based on a standard formula allocated by Principal investigator (two digit institution code, two digit patient identifier, 01-20).

Official Title
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Defining High-Resolution Manometry Thresholds of Backward Pressure Across the Lower Esophageal Sphincter Through Straight Leg Raise Maneuver Predictive of Pathologic Acid Exposure Time

Conditions
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Gastroesophageal Reflux

Intervention / Treatment
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* Procedure: Straight leg raise maneuver


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Complete and adequate HRM and pH-impedance study performed within 2 weeks Successfully performed SLR maneuver (adequate intra-abdominal pressure augmentation) Exclusion Criteria: Patients with prior foregut surgery Obese with BMI>35 Kg/m2 Paraesophageal hiatal hernia Scleroderma Eosinophilic esophagitis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Straight Leg Raise<br>Patients perform straight leg raise maneuver at the end of High-resolution Manometry test | Procedure: Straight leg raise maneuver<br>* With the patient in supine position, one leg is raised to form an angle of at least 45 degrees with the bed. The patient will be asked to keep that position for at least 5 seconds. The maneuver will be repeated after 20-30 seconds. The first adequate maneuver will be considered for the study. Intra-esophageal and intra-abdominal pressure will be analyzed both during baseline and SLR maneuver. Intra-esophageal pressure is measured as peak and mean over 5 seconds, 1 cm and 5 cm above the proximal margin of the LES. Intra-abdominal pressure will be measured as peak and mean over 5 seconds 1 cm below the distal margin of the diaphragm notch.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak esophageal pressure during SLR | Peak esophageal pressure during straight leg raise maneuver, measured 5 cm above the lower esophageal sphincter | Through study completion, an average of 6 months | 
| Mean esophageal pressure during SLR | Mean esophageal pressure during straight leg raise maneuver, measured 5 cm above the lower esophageal sphincter | Through study completion, an average of 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High Resolution Manometry, pH-impedance, Gastroesophageal Reflux disease