Evolution of the Chicago Classification: Bridging Physiology and Mechanics

NCT06883175 | Recruiting

• 1 other identifier: CCv5
• Study Type: interventional
• Target: 575
• Locations: 1 country
• Sites: 1

Brief Summary

Swallowing difficulties are extremely common and result in substantial morbidity, reduction in the quality of life, and mortality related to malnutrition and complications from regurgitation and aspiration. Unfortunately, our understanding regarding the pathophysiology of dysphagia and GERD has been hampered by focusing predominantly on circular muscle activity and ignoring the essential biomechanical properties of the esophageal wall that promote normal emptying. Our initial work explored the relationship between intrabolus pressure (IBP) and esophagogastric junction (EGJ) compliance as a metric for outflow resistance. This work highlighted the direct relationship between IBP and EGJ opening and was the foundation for the development of the classification scheme utilized around the world to diagnose esophageal motor disorders: "the Chicago Classification" (CC). Despite this improved understanding focused on bolus transit dynamics, there are still significant gaps in our scientific understanding centered on the lack of a true correlate for symptoms, reliable predictive models and effective treatments for Functional dysphagia, IEM and EGJOO. Given these limitations, we have developed novel approaches that combine assessments of primary and secondary peristalsis (a NeuroMyogenic Model of esophageal function). These will leverage our recent findings supporting the importance of the esophageal response to distension in bolus clearance, noting that this response of the esophageal wall to bolus retention or reflux is one of the most essential functions of the esophagus in preventing complications of aspiration, or reflux injury. We will also include an assessment of esophageal geometry and wall biomechanics (elasticity/dilatation) as these carry essential interactions with esophageal function that are overlooked in the current diagnostic paradigms. In order to test our hypothesis that wall mechanics are a major determinant of esophageal diseases, we had to develop new approaches and new technology to directly measure mechanical wall state, descending inhibition and LES opening. Using impedance techniques combined with manometry, we are now capable of assessing IBP and diameter changes across a space-time continuum (4D HRM). We also developed physics-based hybrid diagnostics that include a FLIP technique to assess esophageal work and power during volumetric distention (FLIP-MECH) and a fluoroscopy approach that simultaneously assesses esophageal diameter-pressure relationships (Fluoro-MECH). We also developed a new approach, Interactive FLIP Panometry, which facilitates an assessment of descending inhibition and the mechanism behind impaired LES opening. These tools will allow us to expand our models to combine an assessment of neuromyogenic function simultaneously with geometry. Our overarching goal will be to study well-defined patient populations (Functional Dysphagia, IEM/GERD, EGJOO and Achalasia) before and after targeted interventions to test the NeuroMyogenic and MechanoGeometric Model. This work will build upon the previous success of the CC and help advance the evolution of the CC by defining new, relevant biomechanical physiomarkers of disease activity that can identify new targets for therapeutic intervention and facilitate prediction of clinical outcomes.

Conditions

Dysphagia; Achalasia, Esophageal; Ineffective Esophageal Motility

Keywords

dysphagia; swallowing

Outcome Measures

Primary Outcomes (14)

• Brief Esophageal Dysphagia Questionnaire (BEDQ)

  A 10 item dysphagia/food impaction questionnaire measured on a 6-point Likert scale from "none" to "severe" with higher scores indicating a greater degree of dysphagia

  baseline

• Brief Esophageal Dysphagia Questionnaire (BEDQ)

  A 10 item dysphagia/food impaction questionnaire measured on a 6-point Likert scale from "none" to "severe" with higher scores indicating a greater degree of dysphagia

  6 months post-treatment

• Esophagogastric Junction (EGJ) diameter

  Measurement of EGJ diameter in cm

  baseline

• Esophagogastric Junction (EGJ) diameter

  Measurement of EGJ diameter in cm

  6 months post-treatment

• Esophageal Clearance

  Barium column height of 0 cm at 5 minutes

  baseline

• Esophageal Clearance

  Barium column height of 0 cm at 5 minutes

  6 months post-treatment

• recoil

  decrease in wall diameter \>1cm

  baseline

• recoil

  decrease in wall diameter \>1cm

  6 months post-treatment

• Timed Barium Esophagram (TBE) Column Height

  Height of barium column at 5 minutes (Timed Barium Esophagram)

  baseline

• Timed Barium Esophagram (TBE) Column Height

  Height of barium column at 5 minutes (Timed Barium Esophagram)

  6 months post-treatment

• Integrated Relaxation Pressure (IRP)

  Mean EGJ pressure for 4 seconds of relaxation in the ten-second window following deglutitive Upper Esophageal Sphincter relaxation relaxation.

  baseline

• Integrated Relaxation Pressure (IRP)

  Mean EGJ pressure for 4 seconds of relaxation in the ten-second window following deglutitive Upper Esophageal Sphincter relaxation

  6 months post-treatment

• Esophagogastric Junction Distensibility Index

  A measure of the distensibility of the EGJ using Functional Luminal Impedance Probe

  baseline

• Esophagogastric Junction Distensibility Index

  A measure of the distensibility of the EGJ using Functional Luminal Impedance Probe

  6 months post-treatment

Secondary Outcomes (4)

• Bolus Retention

  baseline

• Bolus Retention

  6 months post-treatment

• Eckhart Score

  baseline

• Eckhart Score

  6 months post-treatment

Study Arms (1)

Dysphagia participants

EXPERIMENTAL

There are no arms in this study. All subjects will be studied in like manner.

Diagnostic Test: FLIP; Diagnostic Test: HRM; Other: Prucalopride

Interventions

FLIP DIAGNOSTIC_TEST

Functional Lumen Impedance Planimetry

Dysphagia participants

HRM DIAGNOSTIC_TEST

HIgh Resolution Manometry

Dysphagia participants

Prucalopride OTHER

Medication

Dysphagia participants

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The source of the study population will be male and female subjects aged 18-85 years old inclusive (females of childbearing potential should be on highly effective contraceptive methods) and mentally capable to provide informed consent who present to the Northwestern Medicine Digestive Health Center with the chief complaint of dysphagia, regurgitation, chest pain or food impaction, or referral for treatment of achalasia, GERD, scleroderma, or endoscopy negative dysphagia. All subjects must be able to undergo endoscopy with functional lumen imaging probe (FLIP) and transnasal intubation for 4 dimensional-High Resolution Manometry (4D HRM) and 24-hour pH impedance probe.

You may not qualify if:

• Currently participating in a concurrent clinical trial or completed another trial within past 8 weeks.
• Active severe esophagitis (Los Angeles esophagitis Grade C and above), Patients may be eligible once esophagitis is healed if they continue to have dysphagia in the context of healed esophagitis.
• Contact PD/PI: Pandolfino, John Erik Protection of Human Subjects Page 131
• Evidence of mechanical obstruction due to stricture (e.g., peptic/GERD patients, EoE, or other) or previous small bowel or colonic obstruction.
• Long-segment Barrett's metaplasia.
• Unstable medical illness with ongoing diagnostic work-up and treatment. Patients with well-controlled hypertension, diabetes and a remote history of ischemic heart disease that is deemed stable, as judged by the physician-investigator can be included. EKG will be performed before prucalopride in the 60 patients undergoing Experiment 1a.
• Current drug or alcohol abuse or dependency.
• Current neurologic or cognitive impairment which would make the patient an unsuitable candidate for a research trial.
• Severe mental illness, e.g., uncontrolled major depression with suicidal ideation, active psychosis, diagnosis of schizophrenia-spectrum disorder.
• Pregnant patients.
• Bleeding diathesis or need for anticoagulation that cannot be stopped for endoscopy.

Sponsors & Collaborators

• Northwestern University: lead
• The California Medical Innovations Institute, Inc.: collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Related Publications (67)

• Abdi H, Williams LJ. Principal component analysis. WIREs Computational Statistics. 2010;2(4):433-59. doi: 10.1002/wics.101.

  BACKGROUND

• Cho YK, Lipowska AM, Nicodeme F, Teitelbaum EN, Hungness ES, Johnston ER, Gawron A, Kahrilas PJ, Pandolfino JE. Assessing bolus retention in achalasia using high-resolution manometry with impedance: a comparator study with timed barium esophagram. Am J Gastroenterol. 2014 Jun;109(6):829-35. doi: 10.1038/ajg.2014.61. Epub 2014 Apr 8.

  PMID: 24710506 BACKGROUND

• Halland M, Ravi K, Barlow J, Arora A. Correlation between the radiological observation of isolated tertiary waves on an esophagram and findings on high-resolution esophageal manometry. Dis Esophagus. 2016 Jan;29(1):22-6. doi: 10.1111/dote.12292. Epub 2014 Oct 20.

  PMID: 25327483 BACKGROUND

• Bedell A, Taft TH, Keefer L, Pandolfino J. Development of the Northwestern Esophageal Quality of Life Scale: A Hybrid Measure for Use Across Esophageal Conditions. Am J Gastroenterol. 2016 Apr;111(4):493-9. doi: 10.1038/ajg.2016.20. Epub 2016 Feb 16.

  PMID: 26881974 BACKGROUND

• Cieslak MC, Castelfranco AM, Roncalli V, Lenz PH, Hartline DK. t-Distributed Stochastic Neighbor Embedding (t-SNE): A tool for eco-physiological transcriptomic analysis. Mar Genomics. 2020 Jun;51:100723. doi: 10.1016/j.margen.2019.100723. Epub 2019 Nov 26.

  PMID: 31784353 BACKGROUND

• Acharya S, Kou W, Halder S, Carlson DA, Kahrilas PJ, Pandolfino JE, Patankar NA. Pumping Patterns and Work Done During Peristalsis in Finite-Length Elastic Tubes. J Biomech Eng. 2021 Jul 1;143(7):071001. doi: 10.1115/1.4050284.

  PMID: 33625493 BACKGROUND

• Acharya S, Halder S, Carlson DA, Kou W, Kahrilas PJ, Pandolfino JE, Patankar NA. Assessment of esophageal body peristaltic work using functional lumen imaging probe panometry. Am J Physiol Gastrointest Liver Physiol. 2021 Feb 1;320(2):G217-G226. doi: 10.1152/ajpgi.00324.2020. Epub 2020 Nov 11.

  PMID: 33174457 BACKGROUND

• Halder S, Acharya S, Kou W, Kahrilas PJ, Pandolfino JE, Patankar NA. Mechanics informed fluoroscopy of esophageal transport. Biomech Model Mechanobiol. 2021 Jun;20(3):925-940. doi: 10.1007/s10237-021-01420-0. Epub 2021 Mar 2.

  PMID: 33651206 BACKGROUND

• Barnard AC, Hunt WA, Timlake WP, Varley E. A theory of fluid flow in compliant tubes. Biophys J. 1966 Nov;6(6):717-24. doi: 10.1016/S0006-3495(66)86690-0.

  PMID: 5972373 BACKGROUND

• Holmstrom AL, Campagna RAJ, Cirera A, Carlson DA, Pandolfino JE, Teitelbaum EN, Hungness ES. Intraoperative use of FLIP is associated with clinical success following POEM for achalasia. Surg Endosc. 2021 Jun;35(6):3090-3096. doi: 10.1007/s00464-020-07739-6. Epub 2020 Jul 6.

  PMID: 32632483 BACKGROUND

• Teitelbaum EN, Soper NJ, Pandolfino JE, Kahrilas PJ, Hirano I, Boris L, Nicodeme F, Lin Z, Hungness ES. Esophagogastric junction distensibility measurements during Heller myotomy and POEM for achalasia predict postoperative symptomatic outcomes. Surg Endosc. 2015 Mar;29(3):522-8. doi: 10.1007/s00464-014-3733-1. Epub 2014 Jul 24.

  PMID: 25055891 BACKGROUND

• Yadlapati R, Hungness ES, Pandolfino JE. Complications of Antireflux Surgery. Am J Gastroenterol. 2018 Aug;113(8):1137-1147. doi: 10.1038/s41395-018-0115-7. Epub 2018 Jun 14.

  PMID: 29899438 BACKGROUND

• Fibbe C, Layer P, Keller J, Strate U, Emmermann A, Zornig C. Esophageal motility in reflux disease before and after fundoplication: a prospective, randomized, clinical, and manometric study. Gastroenterology. 2001 Jul;121(1):5-14. doi: 10.1053/gast.2001.25486.

  PMID: 11438489 BACKGROUND

• Paterson WG, Anderson MA, Anand N. Pharmacological characterization of lower esophageal sphincter relaxation induced by swallowing, vagal efferent nerve stimulation, and esophageal distention. Can J Physiol Pharmacol. 1992 Jul;70(7):1011-5. doi: 10.1139/y92-139.

  PMID: 1360326 BACKGROUND

• Paterson WG. Esophageal and lower esophageal sphincter response to balloon distention in patients with achalasia. Dig Dis Sci. 1997 Jan;42(1):106-12. doi: 10.1023/a:1018893206926.

  PMID: 9009124 BACKGROUND

• Carlson DA, Schauer JM, Kou W, Kahrilas PJ, Pandolfino JE. Functional Lumen Imaging Probe Panometry Helps Identify Clinically Relevant Esophagogastric Junction Outflow Obstruction per Chicago Classification v4.0. Am J Gastroenterol. 2023 Jan 1;118(1):77-86. doi: 10.14309/ajg.0000000000001980. Epub 2022 Aug 23.

  PMID: 36002925 BACKGROUND

• Bredenoord AJ, Babaei A, Carlson D, Omari T, Akiyama J, Yadlapati R, Pandolfino JE, Richter J, Fass R. Esophagogastric junction outflow obstruction. Neurogastroenterol Motil. 2021 Sep;33(9):e14193. doi: 10.1111/nmo.14193. Epub 2021 Jun 12.

  PMID: 34120375 BACKGROUND

• Agrawal A, Hila A, Tutuian R, Mainie I, Castell DO. Bethanechol improves smooth muscle function in patients with severe ineffective esophageal motility. J Clin Gastroenterol. 2007 Apr;41(4):366-70. doi: 10.1097/01.mcg.0000225542.03880.68.

  PMID: 17413603 BACKGROUND

• Jandee S, Geeraerts A, Geysen H, Rommel N, Tack J, Vanuytsel T. Management of Ineffective Esophageal Hypomotility. Front Pharmacol. 2021 May 26;12:638915. doi: 10.3389/fphar.2021.638915. eCollection 2021.

  PMID: 34122066 BACKGROUND

• Kessing BF, Smout AJ, Bennink RJ, Kraaijpoel N, Oors JM, Bredenoord AJ. Prucalopride decreases esophageal acid exposure and accelerates gastric emptying in healthy subjects. Neurogastroenterol Motil. 2014 Aug;26(8):1079-86. doi: 10.1111/nmo.12359. Epub 2014 May 29.

  PMID: 24891067 BACKGROUND

• Camilleri M, Kerstens R, Rykx A, Vandeplassche L. A placebo-controlled trial of prucalopride for severe chronic constipation. N Engl J Med. 2008 May 29;358(22):2344-54. doi: 10.1056/NEJMoa0800670.

  PMID: 18509121 BACKGROUND

• Lei WY, Hung JS, Liu TT, Yi CH, Chen CL. Influence of prucalopride on esophageal secondary peristalsis in reflux patients with ineffective motility. J Gastroenterol Hepatol. 2018 Mar;33(3):650-655. doi: 10.1111/jgh.13986.

  PMID: 28898473 BACKGROUND

• Yi CH, Lei WY, Hung JS, Liu TT, Chen CL. Effects of prucalopride on esophageal secondary peristalsis in humans. Clin Transl Gastroenterol. 2016 Nov 10;7(11):e202. doi: 10.1038/ctg.2016.58.

  PMID: 27831544 BACKGROUND

• Xiao Y, Kahrilas PJ, Nicodeme F, Lin Z, Roman S, Pandolfino JE. Lack of correlation between HRM metrics and symptoms during the manometric protocol. Am J Gastroenterol. 2014 Apr;109(4):521-6. doi: 10.1038/ajg.2014.13. Epub 2014 Feb 11.

  PMID: 24513804 BACKGROUND

• Taft TH, Carlson DA, Simons M, Zavala S, Hirano I, Gonsalves N, Pandolfino JE. Esophageal Hypervigilance and Symptom-Specific Anxiety in Patients with Eosinophilic Esophagitis. Gastroenterology. 2021 Oct;161(4):1133-1144. doi: 10.1053/j.gastro.2021.06.023. Epub 2021 Jun 19.

  PMID: 34153298 BACKGROUND

• Taft TH, Triggs JR, Carlson DA, Guadagnoli L, Tomasino KN, Keefer L, Pandolfino JE. Validation of the oesophageal hypervigilance and anxiety scale for chronic oesophageal disease. Aliment Pharmacol Ther. 2018 May;47(9):1270-1277. doi: 10.1111/apt.14605. Epub 2018 Mar 12.

  PMID: 29528128 BACKGROUND

• Eckardt VF, Aignherr C, Bernhard G. Predictors of outcome in patients with achalasia treated by pneumatic dilation. Gastroenterology. 1992 Dec;103(6):1732-8. doi: 10.1016/0016-5085(92)91428-7.

  PMID: 1451966 BACKGROUND

• Taft TH, Carlson DA, Triggs J, Craft J, Starkey K, Yadlapati R, Gregory D, Pandolfino JE. Evaluating the reliability and construct validity of the Eckardt symptom score as a measure of achalasia severity. Neurogastroenterol Motil. 2018 Jun;30(6):e13287. doi: 10.1111/nmo.13287. Epub 2018 Jan 8.

  PMID: 29315993 BACKGROUND

• Taft TH, Riehl M, Sodikoff JB, Kahrilas PJ, Keefer L, Doerfler B, Pandolfino JE. Development and validation of the brief esophageal dysphagia questionnaire. Neurogastroenterol Motil. 2016 Dec;28(12):1854-1860. doi: 10.1111/nmo.12889. Epub 2016 Jul 5.

  PMID: 27380834 BACKGROUND

• Halder S, Acharya S, Kou W, Campagna RAJ, Triggs JR, Carlson DA, Aadam AA, Hungness ES, Kahrilas PJ, Pandolfino JE, Patankar NA. Myotomy technique and esophageal contractility impact blown-out myotomy formation in achalasia: an in silico investigation. Am J Physiol Gastrointest Liver Physiol. 2022 May 1;322(5):G500-G512. doi: 10.1152/ajpgi.00281.2021. Epub 2022 Feb 16.

  PMID: 35170365 BACKGROUND

• Triggs JR, Krause AJ, Carlson DA, Donnan EN, Campagna RAJ, Jain AS, Kahrilas PJ, Hungness ES, Pandolfino JE. Blown-out myotomy: an adverse event of laparoscopic Heller myotomy and peroral endoscopic myotomy for achalasia. Gastrointest Endosc. 2021 Apr;93(4):861-868.e1. doi: 10.1016/j.gie.2020.07.041. Epub 2020 Jul 25.

  PMID: 32721488 BACKGROUND

• Nabi Z, Talukdar R, Mandavdhare H, Reddy DN. Short versus long esophageal myotomy during peroral endoscopic myotomy: A systematic review and meta-analysis of comparative trials. Saudi J Gastroenterol. 2022 Jul-Aug;28(4):261-267. doi: 10.4103/sjg.sjg_438_21.

  PMID: 34806659 BACKGROUND

• Nabi Z, Ramchandani M, Sayyed M, Chavan R, Darisetty S, Goud R, Murthy HVV, Reddy DN. Comparison of Short Versus Long Esophageal Myotomy in Cases With Idiopathic Achalasia: A Randomized Controlled Trial. J Neurogastroenterol Motil. 2021 Jan 30;27(1):63-70. doi: 10.5056/jnm20022.

  PMID: 32675389 BACKGROUND

• Sifrim D, Janssens J. Secondary peristaltic contractions, like primary peristalsis, are preceded by inhibition in the human esophageal body. Digestion. 1996;57(1):73-8. doi: 10.1159/000201316.

  PMID: 8626052 BACKGROUND

• Halder S, Pandolfino JE, Kahrilas PJ, Koop A, Schauer J, Araujo IK, Elisha G, Kou W, Patankar NA, Carlson DA. Assessing mechanical function of peristalsis with functional lumen imaging probe panometry: Contraction power and displaced volume. Neurogastroenterol Motil. 2023 Dec;35(12):e14692. doi: 10.1111/nmo.14692. Epub 2023 Oct 16.

  PMID: 37845833 BACKGROUND

• Acharya S, Halder S, Carlson DA, Kou W, Kahrilas PJ, Pandolfino JE, Patankar NA. Estimation of mechanical work done to open the esophagogastric junction using functional lumen imaging probe panometry. Am J Physiol Gastrointest Liver Physiol. 2021 May 1;320(5):G780-G790. doi: 10.1152/ajpgi.00032.2021. Epub 2021 Mar 3.

  PMID: 33655760 BACKGROUND

• Kou W, Carlson DA, Patankar NA, Kahrilas PJ, Pandolfino JE. Four-dimensional impedance manometry derived from esophageal high-resolution impedance-manometry studies: a novel analysis paradigm. Therap Adv Gastroenterol. 2020 Oct 24;13:1756284820969050. doi: 10.1177/1756284820969050. eCollection 2020.

  PMID: 33178334 BACKGROUND

• Carlson DA, Kahrilas PJ, Lin Z, Hirano I, Gonsalves N, Listernick Z, Ritter K, Tye M, Ponds FA, Wong I, Pandolfino JE. Evaluation of Esophageal Motility Utilizing the Functional Lumen Imaging Probe. Am J Gastroenterol. 2016 Dec;111(12):1726-1735. doi: 10.1038/ajg.2016.454. Epub 2016 Oct 11.

  PMID: 27725650 BACKGROUND

• Vespa E, Farina DA, Kahrilas PJ, Kou W, Low EE, Yadlapati R, Pandolfino JE, Carlson DA. Identifying spastic variant of type II achalasia after treatment with high-resolution manometry and FLIP Panometry. Neurogastroenterol Motil. 2023 Jul;35(7):e14552. doi: 10.1111/nmo.14552. Epub 2023 Feb 21.

  PMID: 36807659 BACKGROUND

• Low EE, Fehmi SA, Hasan A, Chang M, Kwong W, Krinsky ML, Anand G, Greytak M, Kaizer A, Carlson DA, Pandolfino JE, Yadlapati R. Type II achalasia with focal elevated pressures: A distinct manometric and clinical sub-group. Neurogastroenterol Motil. 2022 Dec;34(12):e14449. doi: 10.1111/nmo.14449. Epub 2022 Aug 16.

  PMID: 35972282 BACKGROUND

• Rohof WO, Salvador R, Annese V, Bruley des Varannes S, Chaussade S, Costantini M, Elizalde JI, Gaudric M, Smout AJ, Tack J, Busch OR, Zaninotto G, Boeckxstaens GE. Outcomes of treatment for achalasia depend on manometric subtype. Gastroenterology. 2013 Apr;144(4):718-25; quiz e13-4. doi: 10.1053/j.gastro.2012.12.027. Epub 2012 Dec 28.

  PMID: 23277105 BACKGROUND

• Pandolfino JE, Kwiatek MA, Nealis T, Bulsiewicz W, Post J, Kahrilas PJ. Achalasia: a new clinically relevant classification by high-resolution manometry. Gastroenterology. 2008 Nov;135(5):1526-33. doi: 10.1053/j.gastro.2008.07.022. Epub 2008 Jul 22.

  PMID: 18722376 BACKGROUND

• Richardson C, Agrawal R, Lee J, Almagor O, Nelson R, Varga J, Cuttica MJ, Dematte JD, Chang RW, Hinchcliff ME. Esophageal dilatation and interstitial lung disease in systemic sclerosis: A cross-sectional study. Semin Arthritis Rheum. 2016 Aug;46(1):109-14. doi: 10.1016/j.semarthrit.2016.02.004. Epub 2016 Feb 26.

  PMID: 27033049 BACKGROUND

• Jain AS, Carlson DA, Triggs J, Tye M, Kou W, Campagna R, Hungness E, Kim D, Kahrilas PJ, Pandolfino JE. Esophagogastric Junction Distensibility on Functional Lumen Imaging Probe Topography Predicts Treatment Response in Achalasia-Anatomy Matters! Am J Gastroenterol. 2019 Sep;114(9):1455-1463. doi: 10.14309/ajg.0000000000000137.

  PMID: 30741739 BACKGROUND

• Carlson DA, Prescott JE, Germond E, Brenner D, Carns M, Correia CS, Tetreault MP, McMahan ZH, Hinchcliff M, Kou W, Kahrilas PJ, Perlman HR, Pandolfino JE. Heterogeneity of primary and secondary peristalsis in systemic sclerosis: A new model of "scleroderma esophagus". Neurogastroenterol Motil. 2022 Jul;34(7):e14284. doi: 10.1111/nmo.14284. Epub 2021 Oct 28.

  PMID: 34709690 BACKGROUND

• Carlson DA, Gyawali CP, Khan A, Yadlapati R, Chen J, Chokshi RV, Clarke JO, Garza JM, Jain AS, Katz P, Konda V, Lynch K, Schnoll-Sussman FH, Spechler SJ, Vela MF, Prescott JE, Baumann AJ, Donnan EN, Kou W, Kahrilas PJ, Pandolfino JE. Classifying Esophageal Motility by FLIP Panometry: A Study of 722 Subjects With Manometry. Am J Gastroenterol. 2021 Dec 1;116(12):2357-2366. doi: 10.14309/ajg.0000000000001532.

  PMID: 34668487 BACKGROUND

• Carlson DA, Kou W, Lin Z, Hinchcliff M, Thakrar A, Falmagne S, Prescott J, Dorian E, Kahrilas PJ, Pandolfino JE. Normal Values of Esophageal Distensibility and Distension-Induced Contractility Measured by Functional Luminal Imaging Probe Panometry. Clin Gastroenterol Hepatol. 2019 Mar;17(4):674-681.e1. doi: 10.1016/j.cgh.2018.07.042. Epub 2018 Aug 3.

  PMID: 30081222 BACKGROUND

• Nguyen AD, Ellison A, Reddy CA, Mendoza R, Podgaetz E, Ward MA, Souza RF, Spechler SJ, Konda VJA. Spastic secondary contractile patterns identified by FLIP panometry in symptomatic patients with unremarkable high-resolution manometry. Neurogastroenterol Motil. 2022 Jul;34(7):e14321. doi: 10.1111/nmo.14321. Epub 2022 Jan 24.

  PMID: 35075734 BACKGROUND

• Omari TI, Zifan A, Cock C, Mittal RK. Distension contraction plots of pharyngeal/esophageal peristalsis: next frontier in the assessment of esophageal motor function. Am J Physiol Gastrointest Liver Physiol. 2022 Sep 1;323(3):G145-G156. doi: 10.1152/ajpgi.00124.2022. Epub 2022 Jul 5.

  PMID: 35788152 BACKGROUND

• Choi JY, Jung KW, Pandolfino JE, Choi K, Park YS, Na HK, Ahn JY, Lee JH, Kim DH, Choi KD, Song HJ, Lee GH, Jung HY. Dysphagia associated with esophageal wall thickening in patients with nonspecific high-resolution manometry findings: Understanding motility beyond the Chicago classification version 4.0. Neurogastroenterol Motil. 2024 Apr;36(4):e14736. doi: 10.1111/nmo.14736. Epub 2024 Jan 15.

  PMID: 38225864 BACKGROUND

• Carlson DA, Lin Z, Rogers MC, Lin CY, Kahrilas PJ, Pandolfino JE. Utilizing functional lumen imaging probe topography to evaluate esophageal contractility during volumetric distention: a pilot study. Neurogastroenterol Motil. 2015 Jul;27(7):981-9. doi: 10.1111/nmo.12572. Epub 2015 Apr 20.

  PMID: 25898916 BACKGROUND

• Lin Z, Yim B, Gawron A, Imam H, Kahrilas PJ, Pandolfino JE. The four phases of esophageal bolus transit defined by high-resolution impedance manometry and fluoroscopy. Am J Physiol Gastrointest Liver Physiol. 2014 Aug 15;307(4):G437-44. doi: 10.1152/ajpgi.00148.2014. Epub 2014 Jun 26.

  PMID: 24970774 BACKGROUND

• Kou W, Carlson DA, Kahrilas PJ, Patankar NA, Pandolfino JE. Normative values of intra-bolus pressure and esophageal compliance based on 4D high-resolution impedance manometry. Neurogastroenterol Motil. 2022 Oct;34(10):e14423. doi: 10.1111/nmo.14423. Epub 2022 Jun 5.

  PMID: 35661346 BACKGROUND

• Aziz Q, Fass R, Gyawali CP, Miwa H, Pandolfino JE, Zerbib F. Functional Esophageal Disorders. Gastroenterology. 2016 Feb 15:S0016-5085(16)00178-5. doi: 10.1053/j.gastro.2016.02.012. Online ahead of print.

  PMID: 27144625 BACKGROUND

• Carlson DA, Gyawali CP, Roman S, Vela M, Taft TH, Crowell MD, Ravi K, Triggs JR, Quader F, Prescott J, Lin FTJ, Mion F, Biasutto D, Keefer L, Kahrilas PJ, Pandolfino JE. Esophageal Hypervigilance and Visceral Anxiety Are Contributors to Symptom Severity Among Patients Evaluated With High-Resolution Esophageal Manometry. Am J Gastroenterol. 2020 Mar;115(3):367-375. doi: 10.14309/ajg.0000000000000536.

  PMID: 31990697 BACKGROUND

• Monrroy H, Cisternas D, Bilder C, Ditaranto A, Remes-Troche J, Meixueiro A, Zavala MA, Serra J, Marin I, Ruiz de Leon A, Perez de la Serna J, Hani A, Leguizamo A, Abrahao L, Coello R, Valdovinos MA. The Chicago Classification 3.0 Results in More Normal Findings and Fewer Hypotensive Findings With No Difference in Other Diagnoses. Am J Gastroenterol. 2017 Apr;112(4):606-612. doi: 10.1038/ajg.2017.10. Epub 2017 Jan 31.

  PMID: 28139656 BACKGROUND

• Clouse RE, Staiano A. Topography of the esophageal peristaltic pressure wave. Am J Physiol. 1991 Oct;261(4 Pt 1):G677-84. doi: 10.1152/ajpgi.1991.261.4.G677.

  PMID: 1928353 BACKGROUND

• Halder S, Yamasaki J, Acharya S, Kou W, Elisha G, Carlson DA, Kahrilas PJ, Pandolfino JE, Patankar NA. Virtual disease landscape using mechanics-informed machine learning: Application to esophageal disorders. Artif Intell Med. 2022 Dec;134:102435. doi: 10.1016/j.artmed.2022.102435. Epub 2022 Oct 31.

  PMID: 36462900 BACKGROUND

• Koop AH, Kahrilas PJ, Schauer J, Pandolfino JE, Carlson DA. The impact of primary peristalsis, contractile reserve, and secondary peristalsis on esophageal clearance measured by timed barium esophagogram. Neurogastroenterol Motil. 2023 Oct;35(10):e14638. doi: 10.1111/nmo.14638. Epub 2023 Jul 7.

  PMID: 37417394 BACKGROUND

• Carlson DA, Baumann AJ, Donnan EN, Krause A, Kou W, Pandolfino JE. Evaluating esophageal motility beyond primary peristalsis: Assessing esophagogastric junction opening mechanics and secondary peristalsis in patients with normal manometry. Neurogastroenterol Motil. 2021 Oct;33(10):e14116. doi: 10.1111/nmo.14116. Epub 2021 Mar 11.

  PMID: 33705590 BACKGROUND

• Carlson DA, Kou W, Masihi M, Acharya S, Baumann AJ, Donnan EN, Kahrilas PJ, Pandolfino JE. Repetitive Antegrade Contractions: A novel response to sustained esophageal distension is modulated by cholinergic influence. Am J Physiol Gastrointest Liver Physiol. 2020 Oct 7. doi: 10.1152/ajpgi.00305.2020. Online ahead of print.

  PMID: 33026823 BACKGROUND

• Carlson DA, Kathpalia P, Craft J, Tye M, Lin Z, Kahrilas PJ, Pandolfino JE. The relationship between esophageal acid exposure and the esophageal response to volumetric distention. Neurogastroenterol Motil. 2018 Mar;30(3):10.1111/nmo.13240. doi: 10.1111/nmo.13240. Epub 2017 Nov 2.

  PMID: 29098750 BACKGROUND

• Carlson DA, Lin Z, Kahrilas PJ, Sternbach J, Donnan EN, Friesen L, Listernick Z, Mogni B, Pandolfino JE. The Functional Lumen Imaging Probe Detects Esophageal Contractility Not Observed With Manometry in Patients With Achalasia. Gastroenterology. 2015 Dec;149(7):1742-51. doi: 10.1053/j.gastro.2015.08.005. Epub 2015 Aug 14.

  PMID: 26278501 BACKGROUND

• 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.

  PMID: 33373111 BACKGROUND

• Kahrilas PJ, Bredenoord AJ, Fox M, Gyawali CP, Roman S, Smout AJ, Pandolfino JE; International High Resolution Manometry Working Group. The Chicago Classification of esophageal motility disorders, v3.0. Neurogastroenterol Motil. 2015 Feb;27(2):160-74. doi: 10.1111/nmo.12477. Epub 2014 Dec 3.

  PMID: 25469569 BACKGROUND

• Pandolfino JE, Ghosh SK, Rice J, Clarke JO, Kwiatek MA, Kahrilas PJ. Classifying esophageal motility by pressure topography characteristics: a study of 400 patients and 75 controls. Am J Gastroenterol. 2008 Jan;103(1):27-37. doi: 10.1111/j.1572-0241.2007.01532.x. Epub 2007 Sep 26.

  PMID: 17900331 BACKGROUND

• Peery AF, Crockett SD, Murphy CC, Jensen ET, Kim HP, Egberg MD, Lund JL, Moon AM, Pate V, Barnes EL, Schlusser CL, Baron TH, Shaheen NJ, Sandler RS. Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2021. Gastroenterology. 2022 Feb;162(2):621-644. doi: 10.1053/j.gastro.2021.10.017. Epub 2021 Oct 19.

  PMID: 34678215 BACKGROUND

MeSH Terms

Conditions

Deglutition Disorders; Esophageal Achalasia

Interventions

prucalopride

Condition Hierarchy (Ancestors)

Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Esophageal Motility Disorders

Central Study Contacts

John E Pandolfino, MD

CONTACT

3126950182; j-pandolfino@northwestern.edu

Dustin A Carlson, MD

CONTACT

3129264643; dustin.carlson@northwestern.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 25, 2024
• First Posted: March 19, 2025
• Study Start: September 1, 2024
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)