Achalasia
Conditions
Keywords
lower esophageal sphincter, Functional Lumen Imaging Probe Topography, anti-fibrosis agents, anti-inflammatory agents
Brief summary
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
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.
Interventions
DRUGAtropine challenge
Atropine challenge. After baseline FLIP, subjects will be administered 15 mcg/kg of intravenous atropine. Two minutes after administration, FLIP will be repeated.
PROCEDUREEsophageal muscle biopsy
During standard-of-care Heller myotomy, per-oral endoscopic myotomy, or esophagectomy, lower esophageal sphincter and distal esophageal circular muscle samples will be taken with biopsy forceps. 2-3 samples, approximately 2-3 mm each, will be collected.
Sponsors
Emory University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Participants may consent to Aim 1(pharmacologic challenge), Aim 2 (if they undergo a future myotomy), or both aims. After completion of Aim 1 enrollment, participants who are scheduled to undergo Heller myotomy, per-oral endoscopic myotomy (POEM), or esophagectomy for treatment of their esophageal motility disorder may participate in Aim 2 only.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 starting October 1, 2020. * 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 the treatment of their esophageal motility disorder (for Aim 2) * 8 healthy control esophageal samples will be obtained from the NDRI donor program for Aim 2.
Exclusion criteria
* Patients younger than 18 years old * Pregnant women * Prisoners * Non-English-speaking patients - 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. * Cognitively impaired adults unable to provide informed consent * Cardiac disease in the form of - arrhythmia requiring intracardiac defibrillator (ICD) or pacemaker, baseline bradycardia with HR \<60 or tachycardia with a heart rate (HR) \> 90, congestive heart failure with ejection fraction \<35%, history of myocardial infarction, baseline mean arterial pressure (MAP) \<65 or systolic blood pressure (BP) \>140, asthma or chronic obstructive pulmonary disease, urinary retention requiring the use of foley catheterization (including intermittent use), narrow-angle glaucoma, myasthenia gravis, glomerular filtration rate (GFR) \<60 \[exclusions for Aim 1 only\]
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Degree of lower esophageal sphincter contraction and relaxation | Two minutes after the study drugs administration | Degree of lower esophageal sphincter contraction and relaxation will be measured |
| The collagen content in muscle biopsy specimens | Two minutes after the study drugs administration | The collagen content in muscle biopsy specimens will be measured on Sirius Red and Masson Trichrome staining. |
Countries
United States
Contacts
CONTACTAnand Jain, MD
PRINCIPAL_INVESTIGATORAnand Jain, MD
Emory University
Outcome results
None listed