DysphagiaNCT06883175
Evolution of the Chicago Classification: Bridging Physiology and Mechanics
A study testing FLIP, HRM and Prucalopride in people with Dysphagia and Achalasia, Esophageal, run by Northwestern University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Dysphagia, Achalasia, Esophageal, Ineffective Esophageal Motility
- What is being tested?
- FLIP, HRM and Prucalopride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 575 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2024to 30 Jun 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Dustin A Carlson, MD, 3129264643, dustin.carlson@northwestern.edu
Christine E Nelson, MS, 3126952742, c-ebert@northwestern.edu
About this study
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.
Read the detailed description
The proposed experiments in this application will utilize both standard of care diagnostic testing and treatment as well as research procedures in small subsets of participants as required for each Specific Aim. No randomization will be utilized in any aim. The source of the study population will be male and female subjects aged 18-85 years old inclusive 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, or endoscopy negative dysphagia. These subjects will be approached by the study team and provide informed consent prior to study involvement.
In Aim 1, 375 subjects (300 with FD, IEM, or EGJOO and 75 with GERD) will participate. For Aim 1a, standard of care procedural results and questionnaires will be used to develop the best thresholds that will stage the NeuroMyogenic Model. Sixty of these subjects will undergo open-label treatment with prucalopride (2mg qD (oral) for 2 weeks) with completion of questionnaires (research) after the 2 week time period. Fifteen of these (5 each stage of the Neuromyogenic model- I, II, and III) will complete a post-treatment procedure visit where they will undergo sedated FLIP with manometry and esophagram evaluation with questionnaires on the last day of medication. Sample sizes for this experiment are based on our previous results, where patients with HRM of normal motility, IEM, or AC will yield NeuroMyogenic classification of stage I in 15%, stage II in 15%, and stage III in 10% (with 60% of patients being "normal function dysphagia"), thus sample sizes of n=20 for each group will be feasible for recruitment.
For Aim 1b, we will recruit 50 subjects with IEM/FD with impaired LES Opening on FLIP and 50 with EGJOO and assess the ability of EUS-guided Botox to relieve symptoms as measured by EGJ opening before and after treatment. Additionally, a comparison group of type II achalasia (n=15) without significant dilatation (esophageal width <3cm) will be tested with Interactive FLIP Panometry (Comparison from Aim 2a). Based on our data, we anticipate 20% of 250 patients with HRM of normal motility, IEM, or AC will have abnormal EGJ opening. The response rate to distension and botulinum toxin are not a priori known for EGJOO or FD patients, thus, considering rates from 15-90%, our planned sample size of n=50 per group would provide 80% power to detect absolute differences between groups of 13-27%, which correspond to odds ratios of 3.0-6.9.
For Aim 1c, 75 subjects with GERD will undergo pH-impedance testing, HRM, FLIP and complete PROs as part of their standard of care before and after treatment (fundoplication or MSA). HRM is performed prior to the placement of the pH-Impedance catheter and the HRM procedural data along with FLIP data will be used in this experiment to attempt to predict the likelihood of dysphagia (as measured by BEDQ) after MSA or fundoplication. Assuming 25-50% of patients develop dysphagia and abnormal bolus transit occurs in 13-31% of these patients, our model would have 80% power to detect effects on the order of odds ratios of 2.6-3.3.
Aim 2 experiments focus on achalasia as the disease of interest and explore the role of abnormal geometry and esophageal wall state in determining clinical outcomes of treatment and esophageal emptying. Subjects will be studied using our clinical physiomechanical protocol (EGD, FLIP, HRM, TBE) as part of their standard of care before and 6 months after short tailored POEM. Two hundred subjects will be studied. The primary outcomes will be esophageal clearance and recoil (elasticity) in 100 subjects for experiment 2a. These data will be subject to a supervised learning method to define thresholds for defining the stages of achalasia. The planned cohort sizes (n=100) have traditionally been sufficient for fitting and evaluating SVM.
In experiment 2b, the SOC information will be collected from all 200 subjects and used to measure the primary outcome of treatment success defined as Eckart Score <3 and TBE 5-min column height <5cm (without re-intervention). We will study the success of POEM when the EGJ-Distensibility threshold is set at 3.0. Patients who fail will undergo repeat POEM to a target EGJ-DI of 6.0. We theorize that the higher stages will require a higher target for EGJ-DI. Assuming up to 10% attrition, GLM using all n=200 patients would have 80% power to detect differences in treatment response rates across up to 5 stages consistent with those rates ranging from 60-90%.
- Being tested
- FLIP, HRM, Prucalopride
- Keywords
- dysphagia, swallowing
- Medical subject headings
- Deglutition Disorders, Esophageal Achalasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FLIPDiagnostic test
Functional Lumen Impedance Planimetry
HRMDiagnostic test
HIgh Resolution Manometry
PrucaloprideOther
Medication
| Study group | Role | What they receive |
|---|---|---|
| Dysphagia participants | Experimental | There are no arms in this study. All subjects will be studied in like manner. Receives: Diagnostic Test: FLIP; Diagnostic Test: HRM; Other: Prucalopride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 6 months post-treatment
Esophagogastric Junction (EGJ) diameter
Measurement of EGJ diameter in cm
Measured: baseline
Esophagogastric Junction (EGJ) diameter
Measurement of EGJ diameter in cm
Measured: 6 months post-treatment
Esophageal Clearance
Barium column height of 0 cm at 5 minutes
Measured: baseline
Esophageal Clearance
Barium column height of 0 cm at 5 minutes
Measured: 6 months post-treatment
recoil
decrease in wall diameter >1cm
Measured: baseline
recoil
decrease in wall diameter >1cm
Measured: 6 months post-treatment
Timed Barium Esophagram (TBE) Column Height
Height of barium column at 5 minutes (Timed Barium Esophagram)
Measured: baseline
Timed Barium Esophagram (TBE) Column Height
Height of barium column at 5 minutes (Timed Barium Esophagram)
Measured: 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.
Measured: baseline
Integrated Relaxation Pressure (IRP)
Mean EGJ pressure for 4 seconds of relaxation in the ten-second window following deglutitive Upper Esophageal Sphincter relaxation
Measured: 6 months post-treatment
Esophagogastric Junction Distensibility Index
A measure of the distensibility of the EGJ using Functional Luminal Impedance Probe
Measured: baseline
Esophagogastric Junction Distensibility Index
A measure of the distensibility of the EGJ using Functional Luminal Impedance Probe
Measured: 6 months post-treatment
Secondary outcomes (4)
Bolus Retention
A combined measurement of barium column height (in cm) at 5 minutes (Timed Barium Esophagram) and Impedance Bolus Height (4D HRM)
Measured: baseline
Bolus Retention
A combined measurement of barium column height (in cm) at 5 minutes (Timed Barium Esophagram) and Impedance Bolus Height (4D HRM)
Measured: 6 months post-treatment
Eckhart Score
A 4-item self-report scale measuring weight loss, chest pain, regurgitation, and Dysphagia. Scores range 0-4, lower is better.
chest pain, regurgitation, and dysphagia
Measured: baseline
Eckhart Score
A 4-item self-report scale measuring weight loss, chest pain, regurgitation, and Dysphagia. Scores range 0-4, lower is better.
chest pain, regurgitation, and dysphagia
Measured: 6 months post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2025
- Study start1 Sep 2024
- Primary completion30 Jun 2029 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (67)Papers the sponsor has linked to this study.
- Other trials for DysphagiaStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 575 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- The California Medical Innovations Institute, Inc.
- Responsible party
- Principal investigator, John Pandolfino, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06883175
- Sponsor's protocol ID
- CCv5
- Status last verified
- Sep 2026
- First submitted
- 25 Nov 2024
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Abdi H, Williams LJ. Principal component analysis. WIREs Computational Statistics. 2010;2(4):433-59. doi: 10.1002/wics.101.
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.
PubMed 24710506Halland 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.
PubMed 25327483Bedell 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.
PubMed 26881974Cieslak 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.
PubMed 31784353Acharya 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.
PubMed 33625493Acharya 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.
PubMed 33174457Halder 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.
PubMed 33651206Barnard 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.
PubMed 5972373Holmstrom 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.
PubMed 32632483Teitelbaum 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.
PubMed 25055891Yadlapati 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.
PubMed 29899438Fibbe 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.
PubMed 11438489Paterson 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.
PubMed 1360326Paterson 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.
PubMed 9009124
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evolution of the Chicago Classification: Bridging Physiology and Mechanics
- ClinicalTrials.gov ID
- NCT06883175
- Acronym / sponsor ID
- CCv5
- Keywords
- dysphagia, swallowing
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 575 participants (estimated)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- The California Medical Innovations Institute, Inc.
- Study start
- 1 Sep 2024 (actual)
- Primary completion
- 30 Jun 2029 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 19 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The proposed experiments in this application will utilize both standard of care diagnostic testing and treatment as well as research procedures in small subsets of participants as required for each Specific Aim. No randomization will be utilized in any aim. The source of the study population will be male and female subjects aged 18-85 years old inclusive 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, or endoscopy negative dysphagia. These subjects will be approached by the study team and provide informed consent prior to study involvement.
In Aim 1, 375 subjects (300 with FD, IEM, or EGJOO and 75 with GERD) will participate. For Aim 1a, standard of care procedural results and questionnaires will be used to develop the best thresholds that will stage the NeuroMyogenic Model. Sixty of these subjects will undergo open-label treatment with prucalopride (2mg qD (oral) for 2 weeks) with completion of questionnaires (research) after the 2 week time period. Fifteen of these (5 each stage of the Neuromyogenic model- I, II, and III) will complete a post-treatment procedure visit where they will undergo sedated FLIP with manometry and esophagram evaluation with questionnaires on the last day of medication. Sample sizes for this experiment are based on our previous results, where patients with HRM of normal motility, IEM, or AC will yield NeuroMyogenic classification of stage I in 15%, stage II in 15%, and stage III in 10% (with 60% of patients being "normal function dysphagia"), thus sample sizes of n=20 for each group will be feasible for recruitment.
For Aim 1b, we will recruit 50 subjects with IEM/FD with impaired LES Opening on FLIP and 50 with EGJOO and assess the ability of EUS-guided Botox to relieve symptoms as measured by EGJ opening before and after treatment. Additionally, a comparison group of type II achalasia (n=15) without significant dilatation (esophageal width <3cm) will be tested with Interactive FLIP Panometry (Comparison from Aim 2a). Based on our data, we anticipate 20% of 250 patients with HRM of normal motility, IEM, or AC will have abnormal EGJ opening. The response rate to distension and botulinum toxin are not a priori known for EGJOO or FD patients, thus, considering rates from 15-90%, our planned sample size of n=50 per group would provide 80% power to detect absolute differences between groups of 13-27%, which correspond to odds ratios of 3.0-6.9.
For Aim 1c, 75 subjects with GERD will undergo pH-impedance testing, HRM, FLIP and complete PROs as part of their standard of care before and after treatment (fundoplication or MSA). HRM is performed prior to the placement of the pH-Impedance catheter and the HRM procedural data along with FLIP data will be used in this experiment to attempt to predict the likelihood of dysphagia (as measured by BEDQ) after MSA or fundoplication. Assuming 25-50% of patients develop dysphagia and abnormal bolus transit occurs in 13-31% of these patients, our model would have 80% power to detect effects on the order of odds ratios of 2.6-3.3.
Aim 2 experiments focus on achalasia as the disease of interest and explore the role of abnormal geometry and esophageal wall state in determining clinical outcomes of treatment and esophageal emptying. Subjects will be studied using our clinical physiomechanical protocol (EGD, FLIP, HRM, TBE) as part of their standard of care before and 6 months after short tailored POEM. Two hundred subjects will be studied. The primary outcomes will be esophageal clearance and recoil (elasticity) in 100 subjects for experiment 2a. These data will be subject to a supervised learning method to define thresholds for defining the stages of achalasia. The planned cohort sizes (n=100) have traditionally been sufficient for fitting and evaluating SVM.
In experiment 2b, the SOC information will be collected from all 200 subjects and used to measure the primary outcome of treatment success defined as Eckart Score <3 and TBE 5-min column height <5cm (without re-intervention). We will study the success of POEM when the EGJ-Distensibility threshold is set at 3.0. Patients who fail will undergo repeat POEM to a target EGJ-DI of 6.0. We theorize that the higher stages will require a higher target for EGJ-DI. Assuming up to 10% attrition, GLM using all n=200 patients would have 80% power to detect differences in treatment response rates across up to 5 stages consistent with those rates ranging from 60-90%.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dysphagia participants | Experimental | Diagnostic Test: FLIP, Diagnostic Test: HRM, Other: PrucaloprideThere are no arms in this study. All subjects will be studied in like manner. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (11 listed)
- Currently participating in a concurrent clinical trial or completed another trial within past 8 weeks.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FLIPFunctional Lumen Impedance Planimetry | Diagnostic test | Dysphagia participants |
| HRMHIgh Resolution Manometry | Diagnostic test | Dysphagia participants |
| PrucaloprideMedication | Other | Dysphagia participants |
Primary outcome
Brief Esophageal Dysphagia Questionnaire (BEDQ)
Time frame: baseline
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
Brief Esophageal Dysphagia Questionnaire (BEDQ)
Time frame: 6 months post-treatment
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
Esophagogastric Junction (EGJ) diameter
Time frame: baseline
Measurement of EGJ diameter in cm
Esophagogastric Junction (EGJ) diameter
Time frame: 6 months post-treatment
Measurement of EGJ diameter in cm
Esophageal Clearance
Time frame: baseline
Barium column height of 0 cm at 5 minutes
Esophageal Clearance
Time frame: 6 months post-treatment
Barium column height of 0 cm at 5 minutes
recoil
Time frame: baseline
decrease in wall diameter >1cm
recoil
Time frame: 6 months post-treatment
decrease in wall diameter >1cm
Timed Barium Esophagram (TBE) Column Height
Time frame: baseline
Height of barium column at 5 minutes (Timed Barium Esophagram)
Timed Barium Esophagram (TBE) Column Height
Time frame: 6 months post-treatment
Height of barium column at 5 minutes (Timed Barium Esophagram)
Integrated Relaxation Pressure (IRP)
Time frame: baseline
Mean EGJ pressure for 4 seconds of relaxation in the ten-second window following deglutitive Upper Esophageal Sphincter relaxation relaxation.
Integrated Relaxation Pressure (IRP)
Time frame: 6 months post-treatment
Mean EGJ pressure for 4 seconds of relaxation in the ten-second window following deglutitive Upper Esophageal Sphincter relaxation
Esophagogastric Junction Distensibility Index
Time frame: baseline
A measure of the distensibility of the EGJ using Functional Luminal Impedance Probe
Esophagogastric Junction Distensibility Index
Time frame: 6 months post-treatment
A measure of the distensibility of the EGJ using Functional Luminal Impedance Probe
4 secondary outcomes
Bolus Retention
Time frame: baseline
Bolus Retention
Time frame: 6 months post-treatment
Eckhart Score
Time frame: baseline
Eckhart Score
Time frame: 6 months post-treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
- BackgroundAbdi H, Williams LJ. Principal component analysis. WIREs Computational Statistics. 2010;2(4):433-59. doi: 10.1002/wics.101.
- Background: PubMed 24710506Cho 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.
- Background: PubMed 25327483Halland 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.
- Background: PubMed 26881974Bedell 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.
- Background: PubMed 31784353Cieslak 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.
- Background: PubMed 33625493Acharya 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.
- Background: PubMed 33174457Acharya 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.
- Background: PubMed 33651206Halder 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.
- Background: PubMed 5972373Barnard 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.
- Background: PubMed 32632483Holmstrom 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.
- Background: PubMed 25055891Teitelbaum 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.
- Background: PubMed 29899438Yadlapati 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing FLIP, HRM and Prucalopride in people with Dysphagia and Achalasia, Esophageal, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact John E Pandolfino, MD (3126950182, j-pandolfino@northwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brief Esophageal Dysphagia Questionnaire (BEDQ) (time frame: baseline). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06883175, which also lists 67 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.