NCT06883175 · Northwestern University
Evolution of the Chicago Classification: Bridging Physiology and Mechanics
What this study is about
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.
View original scientific description
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.
Interventions
DIAGNOSTIC_TEST
FLIP
Functional Lumen Impedance Planimetry
DIAGNOSTIC_TEST
HRM
HIgh Resolution Manometry
OTHER
Prucalopride
Medication
Primary outcome measures
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
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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.
Exclusion criteria
- 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.
Where
- Chicago, Illinois
Collaborators
The California Medical Innovations Institute, Inc.
Related conditions & keywords
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Data: ClinicalTrials.gov · synced Aug 11, 2025 · Source of record for eligibility and locations