Mucosal Impedance in Eosinophilic Esophagitis and the Effect of Treatment
Phase: NA
Conditions: Eosinophilic Esophagitis
Sponsor: Mayo Clinic

2/2/2015 
Title:  Mucosal impedance in eosinophilic esophagitis and the effect of treatment 
Co-Principal Investigator: David A. Katzka, MD and Karthik Ravi MD 
Co-Investigators:  
 
Study Coordinators:  
 
 
 
 
 
 
 
 
 
 
         
 
 
 
Background: 
Eosinophilic esophagitis (EoE) is a chronic disease characterized by esophageal eosinophilia 
leading to inflammation and fibrosis in response to food antigens.  One of the presumptions in 
this disease is that antigen recognition occurs in the esophagus by dendritic cell recognition and 
generation of a TH2 allergic response.  Although it is speculated that the esophageal epithelium 
increases its permeability to allow for antigen penetration, this is not well proven. 
Mucosal impedance reflects the ability of electric current to flow between two sensors while in 
contact with the epithelium.  An increase in current flow is presumably due to an increase in ions 
and water crossing the membrane, which are good conductors of electricity.  Through this 
technique an overall measure of “leakiness” of the esophageal epithelium is obtained.  This 
increased permeability may reflect epithelial destruction as in erosive esophagitis, a change in 
epithelium from squamous to columnar as in Barrett’s esophagus or in conditions in which there 
are dilated intercellular spaces as has been observed in both gastroesophageal reflux and 
eosinophilic esophagitis. 
While standard diagnostic evaluation for EoE includes upper endoscopy with esophageal 
biopsies, assessment of mucosal impedance is not.  Recently, a new technology has emerged 
allowing for direct assessment of mucosal impedance at the time of routine upper endoscopy.  
Yuksel and colleagues have described use of a 2mm diameter single-channel catheter used 
during the time of EGD which demonstrated lower mucosal impedance in areas of erosive 
esophagitis and in the mucosa of patients with nonerosive reflux disease compared to healthy 
controls.1 In the same manner, mucosal impedance may be lower in patients with EoE, allowing 
for submucosal antigen exposure and the characteristic Th2 response. 
Hypothesis: 
Patient with eosinophilic esophagitis have diminished mucosal impedance, reflecting increased 
permeability to allergens occurring at least in the esophagus and possibly in the buccal mucosa. 
Primary Aim: 

1. Assess mucosal impedance in patients with EoE of both the esophageal and buccal 
mucosa. 
Secondary Aim: 
2. Changes in mucosal impedance in patients with EoE following treatment 
Methods:  
Study Design: 
Patients referred to the Mayo Clinic Rochester either with an establish or suspected 
diagnosis of EoE will be identified.  Those scheduled for clinically indicated upper 
endoscopy for esophageal biopsies either for initial diagnosis or activity assessment of 
EoE will be studied.  After investigation of established or suspected EoE, a total of 75 
patients with confirmed EoE patients.  In addition, patients undergoing clinically 
indicated upper endoscopy for indications either than gastroesophageal reflux or 
dysphagia will be studied as controls.  A total of 10 control patients will be studied. 
Inclusion criteria: 
 
• Adults ages 18-90 undergoing clinically indicated upper endoscopy  
• Patients with EoE, defined as dysphagia with histologic finding of greater than or 
equal to 15 eosinophils per high powered field on esophageal biopsy despite at 
least 6 weeks of twice daily proton pump inhibitor therapy 
• Patients undergoing clinically indicated upper endoscopy for indications other 
than dysphagia or GERD with normal appearing esophageal mucosa. 
 
Exclusion criteria: 
• Medical conditions such as severe heart or lung disease that preclude safe 
performance of endoscopy  
• Patients with conditions known to be associated with esophageal eosinophilia, 
including Crohn’s disease, Churg-Strauss, achalasia, and hypereosinophilic 
syndrome 
• Inability to read due to: Blindness, cognitive dysfunction, or English language 
illiteracy 
 
Study Flow: 
Patient undergoing clinically indicated endoscopy and esophageal biopsies for diagnosis or 
assessing activity of eosinophilic esophagitis will be identified.  In addition, patients undergoing 

clinically indicated upper endoscopy for indications other than dysphagia or GERD will be 
identified: 
  
1. Before commencing the procedure, a baseline impedance will be obtained by asking 
the patient to hold the end of the probe against his/her buccal mucosa for 1  minute 
for an initial reading. 
2. Clinically indicated endoscopic exam will be completed 
3. On withdrawal of the upper endoscope into the esophagus, a 2.13mm mucosal 
impedance catheter (Figure) will be passed through the channel of the standard upper 
endoscope. 
4. The probe will be placed on the esophageal mucosa 5cm above the gastroesophageal 
junction for 5 seconds and recordings obtained. 
5. In patients with suspected or established EoE in whom clinically indicated esophageal 
biopsies are indicated, 2 biopsies will then be obtained at this level. 
6. The scope will then be withdrawn to 10 and 20 cm above the gastroesophageal 
junction and the same procedure including biopsies performed respectively. 
7. In total, six biopsies will be taken which is part of the guideline recommended 
protocol for eosinophilic esophagitis for clinical purposes.  
8. Biopsies in patients undergoing clinically indicated upper endoscopy for indications 
other than GERD or dysphagia in whom biopsies are not ordered will undergo the 
same protocol, except esophageal biopsies will not be obtained. 
 
There is minimal risk associated with this study.  Upper endoscopy carries an approximate 1 in 
3,000 risk of perforation, bleeding, and infection.  As this is a clinically indicated study, there is 
no increased risk from the standpoint of endoscopy for enrolled patients.  The impedance 
catheter measures only 2.13mm in diameter and is flexible with a blunt end.  Given the catheter 
size and the fact that it is passed with direct endoscopic visualization, risk of complications such 
as perforation or bleeding are minimized and are essentially no different than standard EGD with 
esophageal biopsies.  In fact, in the initial description of use of this catheter 69 patients were 
studied with no catheter associated complications were reported.1 In addition, as impedance 
recording requires on average 5 seconds per level to complete, the protocol will lengthen the 
procedure time on average 15 seconds which will not have clinically relevant implications 
regarding need for conscious sedation and procedure related risk. There are no additional risks to 
the subject adding the buccal mucosal impedance testing. 
Impedance testing  
Statistical Analysis: 

As a pilot, ten patients will be studied before and after treatment for eosinophilic esophagitis.  
This number of patients will be increased if there are treatment failures until there is a total of ten 
effectively treated patients studied.  Effective treatment is defined by the elimination of 
esophageal eosinophilia on follow up endoscopic biopsy.  Ten control patients without 
esophageal disease will be studied. 
Primary Endpoint: 
1. Mean and median mucosal impedance in patients with EoE patients compared to controls 
 
Secondary Endpoints: 
2. Maximal mucosal impedance in EoE patients compared to minimal mucosal impedance 
in control patients to determine a potential diagnostic cutoff value 
3. Mean and median mucosal impedance in EoE patients post treatment in comparison to 
pretreatment 
 
 
 

 
 
 
 
 
 
1.  Yuksel ES, Higginbotham T, Slaughter JC, Mabary J, Kavitt RT, Garrett CG, Vaezi MF.  
Use of direct, endoscopic=guided measurements of mucosal impedance in diagnosis of 
gastroesophageal reflux.  Clin Gastroenterol Hepatol 2012;10:1110-3