HRM, FLIP, and Prucalopride for Dysphagia

Overseen By Dustin A Carlson, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northwestern University

Must not be taking: Anticoagulants

Disqualifiers: Severe esophagitis, Barrett's metaplasia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 2 weeks

575 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for individuals experiencing swallowing difficulties, including those with primary achalasia or other related conditions. Participants should have symptoms that align with the study's focus on esophageal motor disorders and be willing to undergo novel diagnostic assessments.

Inclusion Criteria

I am using a reliable method of birth control.

I am mentally able to understand and agree to the study's procedures.

I am experiencing swallowing difficulties, chest pain, or food getting stuck.

Exclusion Criteria

Pregnant patients

Currently participating in a concurrent clinical trial or completed another trial within the past 8 weeks

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo various diagnostic and treatment procedures including prucalopride treatment, FLIP with manometry, and esophagram evaluation

2 weeks

Multiple visits for procedures and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of esophageal clearance and recoil

6 months

Follow-up assessments at 6 months post-treatment

Extension

Participants may undergo additional procedures if initial treatment targets are not met, such as repeat POEM

As needed based on treatment response

Treatment Details

Interventions

• FLIP
• HRM

Trial Overview The trial is testing new approaches like HRM (High-Resolution Manometry), FLIP (Functional Luminal Imaging Probe), and Prucalopride to measure esophageal mechanics and function. It aims to improve diagnosis by combining these techniques with traditional methods.

Participant Groups

Group I: Dysphagia participants Experimental Treatment 3 Interventions

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

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

The California Medical Innovations Institute, Inc.

Collaborator

Trials

4

Recruited

790+