Clinical trial NCT04813029: Thresholds of Straight Leg Raise Maneuver During High-Resolution-Manometry
Official title: Defining High-Resolution Manometry Thresholds of Backward Pressure Across the Lower Esophageal Sphincter Through Straight Leg Raise Maneuver Predictive of Pathologic Acid Exposure Time
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Gastroesophageal Reflux
Keywords: High Resolution Manometry
pH-impedance
Gastroesophageal Reflux disease
Lead sponsor: University of Milan
Sponsor class: OTHER
Collaborators: name: Medical University of Vienna
name: University Hospital Padova
name: University of Missouri, St. Louis
name: Hospital Universiti Sains Malaysia
name: The Oregon Clinic
name: The Functional Gut Clinic
name: University of Texas at Austin
name: University of Athens
name: Ohio State University
name: University of Campania Luigi Vanvitelli
name: Jikei University School of Medicine
First posted: 2021-03-24
Enrollment: 336
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Peak esophageal pressure during SLR
timeFrame: Through study completion, an average of 6 months
measure: Mean esophageal pressure during SLR
timeFrame: Through study completion, an average of 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: San Donato Milanese
country: Italy
facility: IRCCS Policlinico San Donato
state: Milano
Study officials:
affiliation: University of Milan
name: Luigi Bonavina, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rogers BD, Rengarajan A, Ali IA, Hasak SL, Hansalia V, Gyawali CP. Straight leg raise metrics on high-resolution manometry associate with esophageal reflux burden. Neurogastroenterol Motil. 2020 Dec;32(12):e13929. doi: 10.1111/nmo.13929. Epub 2020 Jul 6.
citation: Masuda T, Mittal SK, Kovacs B, Csucska M, Bremner RM. Simple Manometric Index for Comprehensive Esophagogastric Junction Barrier Competency Against Gastroesophageal Reflux. J Am Coll Surg. 2020 May;230(5):744-755e3. doi: 10.1016/j.jamcollsurg.2020.01.034. Epub 2020 Mar 3.
citation: Yadlapati R, Kahrilas PJ, Fox MR, Bredenoord AJ, Prakash Gyawali C, Roman S, Babaei A, Mittal RK, Rommel N, Savarino E, Sifrim D, Smout A, Vaezi MF, Zerbib F, Akiyama J, Bhatia S, Bor S, Carlson DA, Chen JW, Cisternas D, Cock C, Coss-Adame E, de Bortoli N, Defilippi C, Fass R, Ghoshal UC, Gonlachanvit S, Hani A, Hebbard GS, Wook Jung K, Katz P, Katzka DA, Khan A, Kohn GP, Lazarescu A, Lengliner J, Mittal SK, Omari T, Park MI, Penagini R, Pohl D, Richter JE, Serra J, Sweis R, Tack J, Tatum RP, Tutuian R, Vela MF, Wong RK, Wu JC, Xiao Y, Pandolfino JE. Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0(c). Neurogastroenterol Motil. 2021 Jan;33(1):e14058. doi: 10.1111/nmo.14058.
citation: Gyawali CP, Kahrilas PJ, Savarino E, Zerbib F, Mion F, Smout AJPM, Vaezi M, Sifrim D, Fox MR, Vela MF, Tutuian R, Tack J, Bredenoord AJ, Pandolfino J, Roman S. Modern diagnosis of GERD: the Lyon Consensus. Gut. 2018 Jul;67(7):1351-1362. doi: 10.1136/gutjnl-2017-314722. Epub 2018 Feb 3.
citation: van Hoeij FB, Smout AJ, Bredenoord AJ. Predictive value of routine esophageal high-resolution manometry for gastro-esophageal reflux disease. Neurogastroenterol Motil. 2015 Jul;27(7):963-70. doi: 10.1111/nmo.12570. Epub 2015 Apr 30.
citation: Siboni S, Kristo I, Rogers BD, De Bortoli N, Hobson A, Louie B, Lee YY, Tee V, Tolone S, Marabotto E, Visaggi P, Haworth J, Ivy M, Greenan G, Facchini C, Masuda T, Yano F, Perry K, Balasubramanian G, Theodorou D, Triantafyllou T, Cusmai L, Boveri S, Schoppmann SF, Gyawali CP, Bonavina L. Improving the Diagnostic Yield of High-Resolution Esophageal Manometry for GERD: The "Straight Leg-Raise" International Study. Clin Gastroenterol Hepatol. 2023 Jul;21(7):1761-1770.e1. doi: 10.1016/j.cgh.2022.10.008. Epub 2022 Oct 19.