The Effect of Sucralfate Slurry in Patients With Eosinophilic Esophagitis

Eosinophilic Esophagitis Clinical Trial

— EoE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02353078
• Other study ID #: 14-008661
• Status: Completed
• Phase: Early Phase 1
• First received: January 26, 2015
• Last updated: October 9, 2017
• Start date: January 2015
• Est. completion date: December 2016

Study information

• Verified date: October 2017
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Eosinophilic Esophagitis
• Esophagitis

Intervention

Drug:
• Sucralfate
Sucralfate slurry 1 gram four times daily for four weeks

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.

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.

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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