An interventional study of FLIP and HRM in Dysphagia, Achalasia, Esophageal and Ineffective Esophageal Motility, sponsored by Northwestern University. Recruiting at 1 site in United States. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2026-09-23.
Sponsored by Northwestern University · Not applicable, Interventional, and Diagnostic
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.
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%.
143 studies on the registry are indexed under Esophageal Achalasia; 44 are open to participants now.
This study's planned enrollment of 575 is above the median of 56 across 95 interventional studies indexed under Esophageal Achalasia.
Browse Esophageal Achalasia studies →Northwestern University is the lead sponsor of 1,423 studies on the registry; 198 are open to participants now.
Of its 105 completed or terminated interventional studies of FDA-regulated products, 78 (74%) have results posted.
Compared within Esophageal Achalasia, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Deglutition Disorders. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
There are no arms in this study. All subjects will be studied in like manner.
Diagnostic Test: FLIP · Diagnostic Test: HRM · Other: Prucalopride
Functional Lumen Impedance Planimetry
HIgh Resolution Manometry
Medication
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
Time frame: 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
Time frame: 6 months post-treatment
Esophagogastric Junction (EGJ) diameter
Measurement of EGJ diameter in cm
Time frame: baseline
Esophagogastric Junction (EGJ) diameter
Measurement of EGJ diameter in cm
Time frame: 6 months post-treatment
Esophageal Clearance
Barium column height of 0 cm at 5 minutes
Time frame: baseline
Esophageal Clearance
Barium column height of 0 cm at 5 minutes
Time frame: 6 months post-treatment
recoil
decrease in wall diameter \>1cm
Time frame: baseline
recoil
decrease in wall diameter \>1cm
Time frame: 6 months post-treatment
Timed Barium Esophagram (TBE) Column Height
Height of barium column at 5 minutes (Timed Barium Esophagram)
Time frame: baseline
Timed Barium Esophagram (TBE) Column Height
Height of barium column at 5 minutes (Timed Barium Esophagram)
Time frame: 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.
Time frame: baseline
Integrated Relaxation Pressure (IRP)
Mean EGJ pressure for 4 seconds of relaxation in the ten-second window following deglutitive Upper Esophageal Sphincter relaxation
Time frame: 6 months post-treatment
Esophagogastric Junction Distensibility Index
A measure of the distensibility of the EGJ using Functional Luminal Impedance Probe
Time frame: baseline
Esophagogastric Junction Distensibility Index
A measure of the distensibility of the EGJ using Functional Luminal Impedance Probe
Time frame: 6 months post-treatment
Bolus Retention
A combined measurement of barium column height (in cm) at 5 minutes (Timed Barium Esophagram) and Impedance Bolus Height (4D HRM)
Time frame: baseline
Bolus Retention
A combined measurement of barium column height (in cm) at 5 minutes (Timed Barium Esophagram) and Impedance Bolus Height (4D HRM)
Time frame: 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
Time frame: 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
Time frame: 6 months post-treatment
Plan to share: No
Started Sep 2024 (actual). Primary completion is estimated for Jun 2029, 57 months after the start.
Of 32 interventional studies with no phase under Esophageal Achalasia, half reached primary completion within 44 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 63. This study's planned 57 months is above that.
How these figures are worked out, and which studies are left out of them.
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