Comprehensive Esophageal Diagnostics Study

Comprehensive Assessment of Histopathologic and Physiologic Profile in Esophageal Motility Disorders

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.

Study Overview

• Status: Recruiting
• Conditions: Achalasia
• Intervention / Treatment: Drug: Atropine challenge; Procedure: Esophageal muscle biopsy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anand Jain, MD; Phone Number: 404-778-3184; Email: anand.jain@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Recruiting
      • Emory Saint Joseph's Hospital
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients, age 18 and above.
2. Evaluated by Emory Digestive Diseases Clinic, Emory Motility Lab, the Emory Endoscopy Unit, or Emory Surgery Department starting October 1, 2020.
3. 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)
4. Undergoing a diagnostic Functional Lumen Imaging Probe (FLIP) study at Emory University Hospital with anesthesia assistance (for Aim 1)
5. Undergoing Heller myotomy or per oral endoscopic myotomy for the treatment of their esophageal motility disorder (for Aim 2)

Exclusion Criteria:

1. Patients younger than 18 years old
2. Pregnant women
3. Prisoners
4. Non-English speaking - the rationale is that the symptom characterization and outcome data are measured on detailed and fairly lengthy (5-7 pages) questionnaires written in English with some medical terms. These are standardized questionnaires with no short forms available.
5. Cognitively impaired adults unable to provide informed consent
6. 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 the use of foley catheterization (including intermittent use), narrow-angle glaucoma, myasthenia gravis, GFR <60 [exclusions for Aim 1 only]

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pharmacologic challenge; Measurement of esophageal response to atropine using functional lumen imaging probe (FLIP)

Drug: Atropine challenge; Atropine challenge. After baseline FLIP, subjects will be administered 15 mcg/kg of intravenous atropine. Two minutes after administration, FLIP will be repeated.; Procedure: Esophageal muscle biopsy; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Anand Jain, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2021
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 18, 2020
• First Submitted That Met QC Criteria: November 18, 2020
• First Posted (Actual): November 24, 2020

Study Record Updates

• Last Update Posted (Estimated): November 7, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: anti-inflammatory agents; lower esophageal sphincter; Functional Lumen Imaging Probe Topography; anti-fibrosis agents
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Achalasia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Anti-Arrhythmia Agents; Adjuvants, Anesthesia; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Parasympatholytics; Mydriatics; Atropine
• Other Study ID Numbers: STUDY00001665; 1K23DK131317-01A1 (U.S. NIH Grant/Contract); 2025P013181 (Other Identifier: Emory IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Esophageal function testing data, symptom questionnaire data, treatments performed, and biospecimen analysis results will be shared.
• IPD Sharing Time Frame: Estimated January 2025.
• IPD Sharing Access Criteria: Collaborators with whom the study team has Data Use Agreements in Place will have access through secure electronic means.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No