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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alginate group | Experimental | Patients in this group will be taking the study medication -- alginate solution in addition to standard of care twice daily proton pump inhibitor therapy |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alginates | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Number | percentage of participants | 18 months |
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Adverse Event Data was collected for eighteen months on each patient who was enrolled in the study. AE data was not collected for the historical control group since they were not actively enrolled onto the study, but their data from previous treatment was used to compare with the active participants.
Definition does not differ.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Puja Elias, Associate Professor, PI for study | Medical University of South Carolina | 8438764269 | eliasps@musc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 5, 2018 | Dec 20, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D005764 | Gastroesophageal Reflux |
| ID | Term |
|---|---|
| D015154 | Esophageal Motility Disorders |
| D003680 | Deglutition Disorders |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
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| ID | Term |
|---|---|
| D000464 | Alginates |
| ID | Term |
|---|---|
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
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This is a pilot prospective cohort study at a single tertiary center who will be compared to historical controls.
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|
| 18 months |
| Physician Decision |
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| BG001 |
| 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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A control group comprised of a historical cohort of patients with dysplastic Barrett's esophagus undergoing EET treatment from 2017 to 2020 were collected. |
|
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| 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. | Posted | Mean | Full Range | number of treatment sessions | 18 months |
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| 0 |
| 22 |
| 0 |
| 22 |
| 0 |
| 22 |
| EG001 | 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. | 0 | 0 | 0 | 0 | 0 | 0 |
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| D004066 | Digestive System Diseases |