The Effect of Sucralfate Slurry in Patients With Eosinophilic Esophagitis (EoE)

The Effect of Sucralfate Slurry on Dilated Intercellular Spaces, Tight Junctions, Mucosal Impedance and Mucosal Activity in Patients With Eosinophilic Esophagitis

Could Sucralfate be a non-steriodal treatment option for patients with Eosinophilic esophagitis?

Study Overview

• Status: Completed
• Conditions: Eosinophilic Esophagitis
• Intervention / Treatment: Drug: Sucralfate; Procedure: Intraluminal Impedance; Device: Intraluminal Impedance

Detailed Description

Eosinophilic esophagitis (EoE) is a Th2 type allergy mediated disease that is characterized by dense esophageal eosinophilia in patients with chronic esophageal symptoms. One of the mechanisms of eosinophilic esophagitis is exposure of food antigens to antigen recognition cells in the esophageal mucosa that initiates a chronic allergy-based inflammatory response [1, 2]. It is believed that this exposure is facilitated through dilation of the intercellular spaces (DIS) between esophageal epithelial cells (termed spongiosis). This is substantiated by several studies which have demonstrated that: first, DIS is commonly found in biopsies from patients with active EoE and reverses with steroid therapy [3]; second, DIS correlates to physiologic demonstration of increased esophageal epithelial permeability as shown through transepithelial small molecule flux in mucosal biopsies appraised in Ussing chambers [4], and third, DIS is associated with decreased expression of specific epithelial tight junction proteins such as filaggrin [3]. Thus, a suggested sequence of events in EoE that leads to allergen initiated inflammation includes down regulation of tight junction proteins, dilation of intercellular spaces in the surface epithelium followed by increased permeability and facilitated exposure to food antigens.

Of the present therapies available, topical steroids and in a subset of EoE patients, proton pump inhibitors may improve epithelial permeability. Unfortunately, in the case of proton pump inhibitors, there is early data suggesting that their therapeutic benefit is not sustained. With the use of steroids, there are fears of what the long term side effects of continued use of swallowed steroids might be. The other alternative treatment, diet exclusion therapy is difficult to tailor to the patient and impractical for most adult patients. As a result, alternative treatments are need for EoE.

Sucralfate is a medication that was developed for the treatment of acid-peptic diseases. It's mechanism of action in healing lesions such as gastroduodenal mucosal ulceration still remains unclear but has been described as a "cytoprotective" agent. Several mechanisms have been suggested to be responsible for this protection. These include: binding to and protection of exposed eroded areas, increased prostaglandin production, improved vascular flow, and increased mucus production. This compound has also been shown to augment potential difference in gastric mucosa suggesting a decreased in ion flow. The investigators have shown in measuring mucosal impedance in EoE, this may be related to closure of intercellular spaces which could make this an attractive therapy for eosinophilic esophagitis. Furthermore, the side effect profile of sucralfate is excellent with little systemic absorption. Sucralfate is a category (B) medication, safe for females of child bearing years.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Patients between the ages of 18 and 80 with eosinophilic esophagitis diagnosed by a combination of compatible symptoms, endoscopic findings, histology, and lack of response to proton pump inhibitors.

Exclusion criteria:

• Medical conditions such as severe heart or lung disease that preclude safe performance of endoscopy
• Pregnant and lactating females will be excluded
• Diabetic patients will be excluded as episodes of hyperglycemia have been reported
• Patient with chronic renal failure/on dialysis will be excluded
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sucralfate; This is a pilot study in which 6 patients with active EoE defined by consensus criteria (ref) who have undergone recent endoscopy will be administered sucralfate slurry 1 gram four times daily for four weeks following which repeat endoscopy with esophageal biopsies will be performed. Patients will be those who had not had medical treatment for EoE or those who have not responded to proton pump inhibitors.	Drug: Sucralfate; Sucralfate slurry 1 gram four times daily for four weeks; Other Names: Carafate
Experimental: Intraluminal Impedance; This procedure involves passing a mucosal impedance probe through the endoscope and gently placing the tip of the probe on the esophageal mucosa. Measurements will be made at 2,5,10 and 15 cm above the gastroesophageal junction. There is no increased risk to the procedure and it adds approximately 2 minutes to the procedure.	Procedure: Intraluminal Impedance; During the initial endoscopy, esophageal mucosal impedance will also be measured. This procedure involves passing a mucosal impedance probe through the endoscope and gently placing the tip of the probe on the esophageal mucosa. Measurements will be made at 2,5,10 and 15 cm above the gastroesophageal junction. There is no increased risk to the procedure and it adds approximately 2 minutes to the procedure.; Other Names: Mucosal Impedance; Device: Intraluminal Impedance; The mucosal impedance probe is a 2.13 mm catheter (tiny tube), called an Intraluminal Impedance, will be passed through the channel of the standard endoscope. There is no increased risk to the procedure and it adds approximately 2 minutes to the procedure.; Other Names: Mucosal Impedance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Effectiveness of Sucralfate treatment in patient's with EoE	• The effect treatment is defined by 50%, 3 of the 6 patients having less < 15 eosinophilia per high power field by in the pathology at the time of follow up endoscopic biopsies.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measuring Mucosal impedance	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 and Eosinophilic esophagitis. The investigators will measure the mucosal impedance at the baseline during the upper endoscopy and at the follow up endoscopy. Comparing these measurement to the eosinophilic count on pathology at baseline and followup.	4 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: David Katzka, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: January 26, 2015
• First Submitted That Met QC Criteria: January 28, 2015
• First Posted (Estimate): February 2, 2015

Study Record Updates

• Last Update Posted (Actual): October 11, 2017
• Last Update Submitted That Met QC Criteria: October 9, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Eosinophilic Esophagitis (EOE)
• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Gastroenteritis; Hypersensitivity; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Eosinophilic Esophagitis; Esophagitis; Gastrointestinal Agents; Anti-Ulcer Agents; Sucralfate
• Other Study ID Numbers: 14-008661