The Impact of Adjuvant Liquid Alginate on Endoscopic Ablation Therapy of Complicated Barrett's Esophagus

The Impact of Adjuvant Liquid Alginate on Endoscopic Ablation Therapy of Complicated Barrett's Esophagus: A Pilot Study

This study evaluates the addition of an alginate based solution to twice daily proton pump inhibitor therapy (PPI) in patients undergoing ablative therapy for dysplastic Barrett's esophagus. The investigators hypothesize that the addition of this medication will help to achieve complete remission of Barrett's over a shorter period of time.

Study Overview

• Status: Completed
• Conditions: Barretts Esophagus With Dysplasia
• Intervention / Treatment: Drug: Alginates

Detailed Description

Barrett's esophagus (BE) is a pre-cancerous condition in the esophagus that results from constant acid exposure and is a precursor to esophageal adenocarcinoma (EAC). Surprisingly, EAC rates continue to rise despite efforts aimed at addressing BE. Patients with dysplastic BE are at increased risk for developing EAC and in high grade dysplasia (HGD), this risk can be as high as 6% per year. For these reasons, these patients are candidates for ablation therapy, either with cryotherapy, endoscopic mucosal resection (EMR), and/or radiofrequency ablation (RFA). In patients receiving ablative therapy, 3-5 treatments are typically required before there is resolution of all Barrett's epithelium while patients remain on twice daily proton pump therapy.

A recent case study by the current authors demonstrated initial failed response of BE with HGD to RFA and subsequently cryotherapy. Only after initiation of a liquid alginate solution (Gaviscon Advance - UK formulation) was there a subsequent rapid and complete response to therapy. This case suggests that liquid alginate provided additional esophageal protection allowing mucosal healing and an overall enhanced response to treatment. This finding is mechanistically plausible given existing evidence demonstrating the carcinogenic properties of bile acids and injurious activity of pepsin in non-acid refluxate, and liquid alginate's unique ability to control these components and inhibit acid reflux. The investigators feel further investigation is warranted in studying the role of adjunct liquid alginate solution in patients undergoing treatment for BE.

The ingredient of interest in is alginic acid (alginate), a polysaccharide found in the cell walls of brown algae. Alginates are unique in their ability to form a protective layer above gastric contents upon exposure to gastric acid, thus limiting exposure of esophageal epithelium to gastric acid, bile acid, pepsin, and other parts of the gastric contents. Concurrently, the bicarbonate in alginate-based solutions forms carbon dioxide in the presence of gastric acid, which converts the gel into foam which floats to the surface of the gastric contents. Hence, alginate solutions form "rafts" which provide a physical barrier to acid reflux, as well as a pH-neutral substitute which refluxes preferentially over gastric acid.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• (1) Age 18 (2) Biopsy-proven complicated BE (low/high grade grade dysplasia or IMC, confirmed by our institution's GI pathologist) As part of standard of care, all patients' biopsies will be confirmed with the institutions' GI pathologist and, either with outside biopsies or from biopsies completed at the primary institution.

Exclusion Criteria:

• 1) Moderate to severe renal impairment, as defined by eGFR< 60 for 2 consecutive readings (2) Lack of capacity for decision-making (3) Allergy to hydroxybenzoates (4) Patients with uncontrolled hypertension or decompensated heart failure (5) Pregnancy- patients of child-bearing potential will be tested. (6) Patients with elevated calcium or potassium on screening laboratory testing (labs completed within the last month)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alginate group; Patients in this group will be taking the study medication -- alginate solution in addition to standard of care twice daily proton pump inhibitor therapy	Drug: Alginates; Liquid Alginate therapy will be added to twice daily PPI regimen. Patients will be asked to take the alginate solution four times daily (following meals and at bedtime) at 10ml/dose.; Other Names: Gaviscon Advance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of treatment	To compare the duration of treatment required to achieve complete endoscopic eradication of BE in patients treated with the combination of PPI and liquid alginate solution vs. those treated with PPI alone	12-18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatments	To compare the number of treatment sessions required to achieve endoscopic eradication of BE in patients treated with the combination of PPI and liquid alginate solution vs. those treated with PPI alone.	12-18 months

Collaborators and Investigators

• Sponsor: Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2017
• Primary Completion (Actual): January 1, 2022
• Study Completion (Actual): January 1, 2022

Study Registration Dates

• First Submitted: June 16, 2017
• First Submitted That Met QC Criteria: June 16, 2017
• First Posted (Actual): June 20, 2017

Study Record Updates

• Last Update Posted (Actual): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: GERD; reflux; proton pump inhibitor; Barrett's; alginate solution
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Gastrointestinal Diseases; Esophageal Diseases; Precancerous Conditions; Barrett Esophagus; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Antacids; Alginate, aluminium hydroxide, magnesium trisilicate, sodium bicarbonate drug combination
• Other Study ID Numbers: Pro00065861

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No