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

Sponsor

Medical University of South Carolina (Other)

Overall Status

Completed

CT.gov ID

NCT03193216

Collaborator

(none)

Enrollment

Location

Arm

52.2

Actual Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Barretts Esophagus With Dysplasia	Drug: Alginates	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a pilot prospective cohort study at a single tertiary center who will be compared to historical controls.This is a pilot prospective cohort study at a single tertiary center who will be compared to historical controls.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 25, 2017

Actual Primary Completion Date :

Jan 1, 2022

Actual Study Completion Date :

Jan 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Duration of treatment [12-18 months]
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

Secondary Outcome Measures

Number of treatments [12-18 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)