Comprehensive Esophageal Diagnostics Study

Study Overview
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Brief Summary
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The prospective clinical trial will study muscle fibrosis in relation to lower esophageal sphincter (LES) measurements on Functional Lumen Imaging Probe (FLIP) Topography (the novel technology that utilizes impedance planimetry) after pharmacologic challenge. A better understanding of achalasia will allow intervention at an earlier stage.

Detailed Description
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Achalasia is a disease characterized by inadequate opening of the lower esophageal sphincter. Achalasia is presumed to be due to neuronal dysfunction (active), however there are other variables such as muscle layer fibrosis (passive) that may contribute, particularly in milder or earlier achalasia variants. A new technology, impedance planimetry, may be able to measure active vs passive features of the lower esophageal sphincter (LES). The prospective clinical trial will study muscle fibrosis in relation to lower esophageal sphincter (LES) measurements on Functional Lumen Imaging Probe (FLIP) Topography (the novel technology that utilizes impedance planimetry) after pharmacologic challenge. A better understanding of achalasia will allow intervention at an earlier stage.

Official Title
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Comprehensive Assessment of Histopathologic and Physiologic Profile in Esophageal Motility Disorders

Conditions
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Achalasia

Intervention / Treatment
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* Drug: Atropine challenge
* Procedure: Esophageal muscle biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients, age 18 and above. Evaluated by Emory Digestive Diseases Clinic, Emory Motility Lab, the Emory Endoscopy Unit, or Emory Surgery Department from October 1, 2020 to September 30, 2023. Has a diagnosis of achalasia or an esophageal motility disorder with confirmed evaluation by one of the following modalities: functional lumen imaging probe (FLIP) or high resolution esophageal manometry (for Aim 1) Undergoing a diagnostic Functional Lumen Imaging Probe (FLIP) study at Emory University Hospital with anesthesia assistance (for Aim 1) Undergoing Heller myotomy or per oral endoscopic myotomy for treatment of their esophageal motility disorder (for Aim 2) Exclusion Criteria: Patients younger than 18 years old Pregnant women Prisoners Non-English speaking - the rationale is that the symptom characterization and outcome data are measured on detailed and fairly lengthy (5-7 pages) of questionnaires written in English with some medical terms. These are standardized questionnaires and do not have short forms available. Cognitively impaired adults unable to provide informed consent Cardiac disease in the form of - arrhythmia requiring ICD or pacemaker, baseline bradycardia with HR <60 or tachycardia with HR > 90, congestive heart failure with ejection fraction <35%, history of myocardial infarction, baseline MAP <65 or systolic BP >140, asthma or chronic obstructive pulmonary disease, urinary retention requiring use of foley catheterization (including intermittent use), narrow angle glaucoma, myasthenia gravis, GFR <60 [exclusions for Aim 1 only]

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients will have the option of consenting for Aim 1(pharmacologic challenge ), Aim 2 (in the event they go for future myotomy) or both if they choose to be included in the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pharmacologic challenge<br>Measurement of esophageal response toatropine using functional lumen imaging probe (FLIP) | Drug: Atropine challenge<br>* Atropine challenge. After baseline FLIP, subjects will be administered 15 mcg/kg of intravenous atropine. Two minutes after administration, FLIP will be repeated.<br>Procedure: Esophageal muscle biopsy<br>* Esophageal muscle biopsy. During standard-of-care Heller myotomy or per-oral endoscopic myotomy, 5mm of lower esophageal sphincter and distal esophageal circular muscle will be collected via biopsy forceps.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of lower esophageal sphincter contraction and relaxation | Degree of lower esophageal sphincter contraction and relaxation will be measured | Two minutes after the study drugs administration | 
| The collagen content in muscle biopsy specimens | The collagen content in muscle biopsy specimens will be measured on Sirius Red and Masson Trichrome staining. | Two minutes after the study drugs administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lower esophageal sphincter, Functional Lumen Imaging Probe Topography, anti-fibrosis agents, anti-inflammatory agents