Assessment of Colonic Epithelial Integrity With Mucosal Impedance
Conditions: Inflammatory Bowel Diseases
Sponsor: Vanderbilt University Medical Center

Assessment of Colonic Epithelial Integrity with Mucosal Impedance 
NCT Number: NCT03165058 
Document Date: August 8th, 2016 
 

 
 
 
 
 
 
 
 
 
 
 
Assessment of Colonic Epithelial Integrity with Mucosal Impedance 
 
 
 
 
 
 
 
 
 
 
 
PI: Yash Choksi, MD 
Vanderbilt University Medical Center  
Gastroenterology, Hepatology, and Nutrition  
 
 

Table of Contents:  
 
1.0 Background  
2.0 Rational and Specific Aims 
3.0 Previous Human Studies  
4.0 Inclusion/Exclusion Criteria  
5.0 Enrollment/Randomization 
6.0 Study Procedures  
7.0 Risks of Investigational Agents/Devices (side effects) 
8.0 Reporting of Adverse Events of Unanticipated Problems involving Risk to 
Participants or Others  
9.0 Study Withdrawal/Discontinuation  
10.0 
Statistical Considerations 
11.0 
Privacy/Confidentiality Issues 
12.0 
Follow-up and Record Retention  
 
 
 

Background:  
 
Inflammatory Bowel Disease (IBD) is a chronic, incurable disease, and its 
pathogenesis is incompletely understood. Over one million individuals in the United 
States, over 200,000 Canadians, and over 2.5 million Europeans are estimated to 
have IBD. In the US, the direct medical cost is estimated to be over 6 billion dollars.  
 
One of the challenges in the management of IBD patients is determining endpoints 
for treatment so as to prevent relapse of disease. Whether to treat patients with a 
goal of clinical remission (the patient's symptoms have improved), endoscopic 
remission (normal appearance of the mucosa during endoscopy), or histologic 
remission (normal appearance of biopsied tissue) can be a difficult decision since 
the medications (i.e. anti-TNF, immunomodulators) used in treatment of IBD all 
have significant side effects. This clinical scenario is common and is a reflection of 
our lack of understanding of the disease process.  
 
Barrier function is suspected to play a role in the pathogenesis of IBD and at this 
time there is no convenient way to measure this in vivo.  The overall goal of this 
project is, therefore, to develop a novel, minimally invasive technology to detect 
mucosal damage based on mucosal conductivity changes in the colon and use those 
measurements as an approximation of barrier function. We predict that these 
measurements will be helpful in predicting relapse in IBD and also serve as a clinical 
endpoint in treatment of IBD.  
 
 
Rationale and Aims:  
 
The intestinal epithelium functions to separate luminal contents from the 
interstitium. Increased intestinal permeability can represent compromise of the 
epithelium's integrity. Prior research has demonstrated that defects in intestinal 
barrier function are associated with inflammatory bowel disease (IBD) and 
increased intestinal permeability can be important in the maintenance of remission 
in IBD patients.   
 
There is currently not a convenient way to measure colonic epithelial barrier 
function in real time. The lactulose/mannitol ratio measures small intestinal 
permeability but both are degraded by colonic bacteria and thus do not measure 
colonic permeability. Confocal endomicroscopy of images taken during colonoscopy 
(also of the small intestine - specifically of the terminal ileum) using a special 
endomicroscope colonoscope has also been shown to predict relapse in IBD 
patients. Imaging, however, required injection of a permeability probe during the 
procedure and then after the procedure the images needed to be analyzed by an 
expert.  
 
In this study, we propose to use a novel, minimally invasive technology to detect 
mucosal damage (i.e. barrier dysfunction) based on mucosal conductivity changes in 

the colonic epithelium. This mucosal impedance (MI) test was developed from 
collaborative work with Sandhill Scientific, Inc. and is already being implemented at 
Vanderbilt University for the assessment of esophageal epithelial integrity. 
 
Our hope is that a greater understanding of barrier function, via measurement of MI, 
in the colon of IBD patients can provide clinically relevant information to help make 
these difficult decisions easier. 
 
 
 
Previous Human Studies:  
 
There have been no previous human studies using this device in the colon.  
 
There have, however, been trials using it in the esophagus. One example is IRB 
#120126.  
 
 
 
Inclusion/Exclusion:  
 
This study will be inclusive of all adults who meet the inclusion/exclusion criteria 
and who are at least 18 years of age through age 99. In order to meet our objectives, 
we anticipate that up to 60 people will be enrolled.  
 
Inclusion criteria:  
A. Men and women over the age of 18 with a diagnosis of IBD (Ulcerative Colitis 
or Crohn's disease).  
B. Men and women undergoing screening colonoscopy (typically age would be 
50 or greater but there are exceptions) 
 
Exclusion criteria 
A. Age < 18 years old 
B. Patient unable to give informed consent 
C. Patients with history of colonic surgeries 
D. Patients with history of colonic motility disorder 
 
 
Enrollment/Randomization:  
 
Patients will be identified by either Dr. Vaezi or Dr. Schwartz. Those patients 
undergoing colonoscopy for either the indication of screening colonoscopy or IBD 
surveillance will be asked, on the day of their colonoscopy, whether they want to 
participate in the study. They will then be consented for the procedure. There will 
not be randomization. 
 

All subjects must sign an informed consent form that complies with the 
requirements of both 21 CFR Part 50 and Health Insurance Portability and 
Accountability Act (HIPAA) before entering the trial. An IRB-approved consent form 
that complies with the requirements of 21 CFR Part 50, including a HIPAA compliant 
authorization form for the use and disclosure of the subject’s protected health 
information, will be used. 
 
 
Study Procedures:  
 
During routine colonoscopy, consented study participants will have a mucosal 
impedance catheter sensor positioned along the mucosal wall to measure resistance 
across the mucosa. The physician will take measurements in each segment of the 
colon, including segments that appear inflamed and normal adjacent areas (up to 10 
locations). To obtain a stable reading, the sensor must remain in contact with the 
mucosa for five seconds. The catheter will be attached to a channeled feed that will 
record measurements on a dedicated computer using a software program designed 
by Sandhill Scientific, Inc. The study procedure will add approximately 1-2 minutes 
of anesthesia time for each participant.  
 
This visit is the only required contact with the research volunteers. No further study 
procedures will be performed, and these subjects will not be contacted by research 
personnel following the visit.  
 
Research material gathered from study participants will be limited to mucosal 
impedance data recorded during the routine colonoscopy. Basic demographic 
information, prior IBD treatments, and prior colonoscopic data will be collected 
from the electronic medical record following the procedure for those patients who 
consented to the research. 
 
Device Description: 
 
A single channel MI measuring rings separated by 0.2mm with a 360 degree 
circumferential design were mounted on a catheter, easily traversed through the working 
channel of an endoscope. The catheter tip has two 2 mm impedance sensors that are 3 
mm apart which will make contact with the mucosa. The catheter tip will extend 5 cm 
from the scope end. The catheter body is manufactured from medical grade polyurethane 
which is routinely used in impedance-pH reflux monitoring catheters and is 
biocompatible. 
 

 
The MI devices are reusable following proper cleaning technique.  The probes are cleaned in the 
Digestive Diseases Motility Center with an enzyme solution (Aseptizyme) and then rinsed.  They 
are placed into Cidex OPA for twelve minutes and then removed from Cidex OPA and rinsed 
with water.  Cidex OPA is considered a high level disinfectant solution. 
 
 
Potential Risks:  
 
General Risks:  
This study does not include interventions outside of what would be encountered for 
the standard care of these patients. The risk for participants in this study is 
theoretically low since the subjects are undergoing routine medical care (i.e. their 
colonoscopy is being done for other indications).  
 
However, participation in the study will increase the amount of time that subjects 
are sedated by approximately 1-2 minutes. Increased exposure to anesthesia could 
potentially result in increased risk to the participant. This is outlined as below:  
Common: Short-term memory loss that is usually brief, feeling drowsy, not being 
able to think clearly, decreased blood pressure and decreased respiratory activity 
(abnormal breathing); 
Uncommon: Very low blood pressure, respiratory insufficiency (not breathing well 
enough to meet your body's needs), nausea and vomiting, abnormal heart rhythms, 
and a severe allergic reaction that could cause death; 
 
Severe, Life-threatening and Rare: Breathing stops completely, the contents of the 
stomach get into the lungs, and low blood pressure that is severe enough to stop the 
heart. 
 
Risks for Breach of Confidentiality:  
There is a potential risk of breach of confidentiality associated with participation in 
any research study.  
 
Minimizing Risks:  
This study does not include interventions outside of what would be encountered for 
the standard care of these patients. Recruitment will be from patients who are seen 

in the Digestive Diseases Center at Vanderbilt University Medical Center. Written 
informed consent will be obtained by research staff in accordance with the 
Vanderbilt Institutional Review Board policy and procedure.  
 
The data will be stored in study specific binders in the GI Clinical Research Office. 
The GI Clinical Research Office is locked when not attended by study staff. Study 
documents will be kept indefinitely and stored in VUMC Storage and Services (VSS).  
The specimen reports also will be collected and kept in research file. The data will 
be coded and entered into a computer generated spreadsheet database. Patient 
confidentiality will be maintained in the computer database by not including any 
patient identifying information. The data will be coded by assigning each patient a 
number which is only accessible to study staff. Coded data will be shared with the 
biostatistician. Only the study staff will have access to participant names.  
 
The PI meets with study staff weekly in order to monitor the progress of the study 
and study/participant issues. The PI will oversee all aspects of study conduct and is 
available to study staff via pager or cell phone.  
 
The PI is responsible for data accuracy and protocol compliance. GI research staff 
will audit study records and monitor the data for accuracy.  
 
Risk/Benefit Ratio:  
No existing techniques can measure mucosal integrity in the colon in real time. This 
information may help direct management of IBD patients while increasing the risk 
of their procedure minimally by extending it by less than three minutes. 
 
 
Adverse Event Reporting:  
All serious and unanticipated adverse events or problems involving risks to subjects 
that may possibly be or are known to be related to the research activity will be 
reported promptly to the IRB office per Vanderbilt University IRB Policy. The PI will 
ensure proper data and safety monitoring for the materials and data used for the 
purposes of this study.  
 
 
Study Withdrawal:  
Patients may choose not to participate in this research study. This decision will not 
alter the routine care administered by the physician or the risks associated with 
standard of care procedures, i.e. colonoscopy. Additionally, the participant will be 
removed from this study if the investigator does not think it is in best interest for 
the patient to be in this study. If the patient is removed from the study he/she will 
be told the reason why. 
 
Statistical Considerations:  
No one has ever measured mucosal impedance in the colon and thus it is unknown 
whether there will be altered impedance in patients with active inflammatory bowel 

disease versus normal tissue. Moreover, if there is a difference, it is not known how 
many patients will be required to show a statistically significant difference. Thus at 
this time, a power calculation cannot be done.  
 
 
Privacy/Confidentiality Issues:  
Subjects will have code numbers and will not be identified by name. Subject 
confidentiality is held strictly in trust by the participating investigators, their staff, 
the sponsor(s), and their agents. This confidentiality extends to the clinical 
information relating to participating subjects.  
 
The study protocol, documentation, data, and all other information generated will 
be held in strict confidence. No information concerning the study or the data will be 
released to any unauthorized third party.  
 
Confidentiality of subjects’ records will be maintained; however, the Vanderbilt 
University Medical Center Institutional Review Board and applicable federal 
regulatory agencies may inspect the research records if needed. If any publications 
result from this study, only group or aggregate information will be published. 
Subject’s name and identity will not be mentioned.  
 
If subjects develop complications from endoscopy, the principal investigator will be 
readily available to assess the condition 24 hours a day and 7 days a week by phone 
or clinic visit or emergency room visit. The pager number, office number, hospital 
emergency room number will be given to the subjects when they are enrolled in the 
study.  
 
Follow-up and Record Retention:  
Follow-up is not required. The coded data collected for the purpose of this study will 
be maintained in a research database and will remain with Dr. Yash Choksi  
indefinitely.