Barretts Esophagus With Dysplasia
Conditions
Keywords
Barrett's, GERD, reflux, alginate solution, proton pump inhibitor
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.
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.
Interventions
DRUGAlginates
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.
Sponsors
Medical University of South Carolina
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a pilot prospective cohort study at a single tertiary center who will be compared to historical controls.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Successful Eradication | 18 months | To compare the percentage of patients who achieved complete endoscopic eradication of dysplastic Barrett's Esophagus(BE) and non-dysplastic BE with the combination of PPI and liquid alginate solution vs. those treated with PPI alone within eighteen months from the start of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatments (Mean) | 18 months | To compare the number of treatment sessions required to achieve endoscopic eradication of dysplastic BE and complete eradication of all BE (dysplastic and non-dysplastic) in patients treated with the combination of PPI and liquid alginate solution vs. those treated with PPI alone.The minimum number of treatments would be 1 and maximum number of treatments in the 18 month period is 8. |
Countries
United States
Participant flow
Pre-assignment details
This study had two groups. An active group with participants receiving alginate along with EET treatment and a historical control group comprised of a historical cohort of patients with dysplastic Barrett's esophagus who had EET treatment from 2017 to 2020. All patients in the historical group were treated by the same expert endoscopists included in the study and were on twice a day PPI therapy alone. Patients were matched by age, race, and length of BE.
Participants by arm
| Arm | Count |
|---|---|
| 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
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. | 24 |
| Historical Control Group A control group comprised of a historical cohort of patients with dysplastic Barrett's esophagus undergoing EET treatment from 2017 to 2020 were collected. | 21 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 4 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 0 |
Baseline characteristics
| Characteristic | Alginate Group | Historical Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 11 Participants | 23 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 10 Participants | 22 Participants |
| Age, Continuous | 61.1 years | 64.9 years | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 21 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 21 Participants | 43 Participants |
| Region of Enrollment United States | 24 participants | 21 participants | 45 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 21 Participants | 16 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 0 |
| other Total, other adverse events | 0 / 22 | 0 / 0 |
| serious Total, serious adverse events | 0 / 22 | 0 / 0 |
Outcome results
Primary
Percentage of Patients With Successful Eradication
To compare the percentage of patients who achieved complete endoscopic eradication of dysplastic Barrett's Esophagus(BE) and non-dysplastic BE with the combination of PPI and liquid alginate solution vs. those treated with PPI alone within eighteen months from the start of treatment.
Time frame: 18 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alginate Group | Percentage of Patients With Successful Eradication | Percentage of patients with eradication of dysplasia | 45.5 percentage of participants |
| Alginate Group | Percentage of Patients With Successful Eradication | Percentage of patients with eradication of all Barretts (dysplasic and non-dysplastic) | 36.4 percentage of participants |
| Historical Control Group | Percentage of Patients With Successful Eradication | Percentage of patients with eradication of dysplasia | 38.1 percentage of participants |
| Historical Control Group | Percentage of Patients With Successful Eradication | Percentage of patients with eradication of all Barretts (dysplasic and non-dysplastic) | 19.04 percentage of participants |
Secondary
Number of Treatments (Mean)
To compare the number of treatment sessions required to achieve endoscopic eradication of dysplastic BE and complete eradication of all BE (dysplastic and non-dysplastic) in patients treated with the combination of PPI and liquid alginate solution vs. those treated with PPI alone.The minimum number of treatments would be 1 and maximum number of treatments in the 18 month period is 8.
Time frame: 18 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Alginate Group | Number of Treatments (Mean) | Average number of treatments to achieve eradication of dysplasia | 3.1 number of treatment sessions |
| Alginate Group | Number of Treatments (Mean) | Average number of treatments to achieve eradication of all Barrett's (dysplastic and non-dysplastic) | 3.75 number of treatment sessions |
| Historical Control Group | Number of Treatments (Mean) | Average number of treatments to achieve eradication of dysplasia | 3.88 number of treatment sessions |
| Historical Control Group | Number of Treatments (Mean) | Average number of treatments to achieve eradication of all Barrett's (dysplastic and non-dysplastic) | 5 number of treatment sessions |