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The trial was terminated prematurely by the sponsor for administrative reasons.
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| Name | Class |
|---|---|
| Actavis Inc. | INDUSTRY |
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The purpose of this protocol is to conduct a pilot study to investigate whether pancreatic enzyme supplementation will improve symptoms in individuals with celiac disease who suffer persistent symptoms despite a gluten free diet. This protocol specifically aims to:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PES, Then Placebo | Other | Participants first received Pancreatic Enzyme Supplementation (PES) for 10 days. PES taken 6 times daily with gluten free meals and snacks. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered. After a washout period of 1 week, they then received placebo tablets (matching PES treatment) 6 times daily for 10 days. |
|
| Placebo, Then PES | Other | Participants first received placebo tablets (matching PES) for 10 days. Placebo was taken 6 times daily with gluten-free meals and snacks. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered. After a washout period of 1 week, they then received PES tablets six times daily for 10 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| pancrelipase | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change of Gastrointestinal Symptoms | The average per individual subject on-treatment score in the Celiac Disease Gastrointestinal Symptom Rating Scale (CeD GSRS) domains of Diarrhea, Indigestion, and Abdominal pain comparing active treatment to placebo (i.e. a paired comparison of CeD GSRS on treatment versus on placebo for each subject). CeD-GSRS: Each individual sub-section of the 15 sub-sections scores from 1 to 7, with greater scores indicating worse symptoms. A total score can range from 15 -105. This is then divided by 15 to obtain the minimum overall CeD-GSRS score of 1 and maximum of 7. It has 3 domains- Abdominal pain, Indigestion and Diarrhea domains, each domain having a score ranging from 1-7. The higher the overall score, the more severe the symptoms. | Measured at end of each 10- day treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation of Baseline Fecal Elastase and Celiac Disease Gastrointestinal Symptom Response at End of PES Treatment | Baseline fecal elastase measurement will be correlated with Celiac Disease Gastrointestinal Symptom Rating Scale (CeD-GSRS) scores at the end of PES treatment period. Celiac Disease Gastrointestinal Symptom Response Scale:scores range from 1 to 7, with greater scores indicating worse symptoms. The minimum score obtainable is 15 and the maximum score obtainable is 105. This is then divided by 15 to obtain the minimum overall CeD-GSRS score of 1 and maximum of 7. It has 3 domains- Abdominal pain, Indigestion and Diarrhea domains, each domain having a score ranging from 1-7. The higher the overall score, the more severe the symptoms. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ciaran Kelly, MD | Beth Israel Deaconess Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23163616 | Background | Kelly CP, Green PH, Murray JA, Dimarino A, Colatrella A, Leffler DA, Alexander T, Arsenescu R, Leon F, Jiang JG, Arterburn LA, Paterson BM, Fedorak RN; Larazotide Acetate Celiac Disease Study Group. Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Aliment Pharmacol Ther. 2013 Jan;37(2):252-62. doi: 10.1111/apt.12147. Epub 2012 Nov 19. | |
| 3123181 |
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21 participants were randomized.
Patients were screened for eligibility between 4/16/2015 and 5/28/2017 at Beth Israel Deaconess Medical Center in Boston Massachusetts
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| ID | Title | Description |
|---|---|---|
| FG000 | PES, Then Placebo | Participants first received Pancreatic Enzyme Supplementation (PES) for 10 days. PES taken 6 times daily with gluten free meals and snacks. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered. After a washout period of 1 week, they then received placebo tablets (matching PES treatment) 6 times daily for 10 days. |
| FG001 | Placebo, Then PES | Participants first received placebo tablets (matching PES) for 10 days. Placebo was taken 6 times daily with gluten-free meals and snacks. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered. After a washout period of 1 week, they then received PES tablets six times daily for 10 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Run-in Washout Period #1 (7 Days) |
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| Treatment Period #1 (10 Days) |
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| Run-in Washout Period #2 (7 Days) |
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| Treatment Period #2 (10 Days) |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Treatments | The treatment phase was comprised of two 10-day treatment periods. The study began with a 7 day washout period followed by Treatment period 1. After 10 day treatment period one all participants received a 7 day washout run-in period. Finally, all patients received a 10 day treatment period 2. Participants were randomized to two groups which were "PES, then Placebo" (n=3) or "Placebo, then PES" (n=9). Per cross-over design, all subjects have received both intervention at the end of the trial. |
| Units | Counts |
|---|---|
| Participants |
|
| 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 | Change of Gastrointestinal Symptoms | The average per individual subject on-treatment score in the Celiac Disease Gastrointestinal Symptom Rating Scale (CeD GSRS) domains of Diarrhea, Indigestion, and Abdominal pain comparing active treatment to placebo (i.e. a paired comparison of CeD GSRS on treatment versus on placebo for each subject). CeD-GSRS: Each individual sub-section of the 15 sub-sections scores from 1 to 7, with greater scores indicating worse symptoms. A total score can range from 15 -105. This is then divided by 15 to obtain the minimum overall CeD-GSRS score of 1 and maximum of 7. It has 3 domains- Abdominal pain, Indigestion and Diarrhea domains, each domain having a score ranging from 1-7. The higher the overall score, the more severe the symptoms. | All participants who completed entire study duration were included in the analysis. A comparison of the within-pair differences (delta) in symptom scores after Pancreatic Enzyme Supplement and Placebo treatment, by the Wilcoxon signed rank test. | Posted | Mean | Standard Deviation | units on a scale | Measured at end of each 10- day treatment period |
|
Patients were followed for 34 days which was the entire duration of the study.
Anticipated and unanticipated deaths, serious adverse events, and other adverse events due to any cause, whether related or unrelated to treatment
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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 | Placebo Treatment | Participants ingested placebo tablets 6 times daily (with meals and 3 snacks) for 10 days. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered. |
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Early termination by the sponsor leading to a small number of subjects analyzed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Caitlin Barrett | BIDMC | 617-667-8266 | cbarret5@bidmc.harvard.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 | Aug 8, 2017 | Jul 16, 2020 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 18, 2017 | Jul 17, 2020 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D002446 | Celiac Disease |
| ID | Term |
|---|---|
| D008286 | Malabsorption Syndromes |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D020799 | Pancrelipase |
| D008049 | Lipase |
| D010447 | Peptide Hydrolases |
| D000681 | Amylases |
| ID | Term |
|---|---|
| D002265 | Carboxylic Ester Hydrolases |
| D004950 | Esterases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
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| Baseline visit (fecal elastase levels measured) and end of PES treatment period (CeD-GSRS scores measured) |
| Change in Celiac Symptom Index Scores | The average per individual subject on-treatment scores in the Celiac Symptom Index (CSI) comparing PES treatment to placebo. For the Celiac Symptom Index: scores range from 16 to 80, with greater scores indicating worse symptoms Leffler DA, Dennis M, Edwards George J, Jamma S, Cook EF, Schuppan D, Kelly CP. A validated disease-specific symptom index for adults with celiac disease. Clin Gastroenterol Hepatol. 2009;7:1328-34. PubMed PMID: 19665584. | Measured at the end of each 10-day treatment period |
| Background |
| Svedlund J, Sjodin I, Dotevall G. GSRS--a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci. 1988 Feb;33(2):129-34. doi: 10.1007/BF01535722. |
| 36687454 | Derived | Yoosuf S, Barrett CG, Papamichael K, Madoff SE, Kurada S, Hansen J, Silvester JA, Therrien A, Singh P, Dennis M, Leffler DA, Kelly CP. Pancreatic enzyme supplementation versus placebo for improvement of gastrointestinal symptoms in non-responsive celiac disease: A cross-over randomized controlled trial. Front Med (Lausanne). 2023 Jan 4;9:1001879. doi: 10.3389/fmed.2022.1001879. eCollection 2022. |
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| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
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| Race (NIH/OMB) | Count of Participants | Participants | No |
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| Region of Enrollment | Number | participants |
|
| Baseline Celiac Disease Gastrointestinal Symptom (CeD-GSRS)Response Scale | Celiac Disease Gastrointestinal Symptom Response Scale:scores range from 1 to 7, with greater scores indicating worse symptoms. The minimum score obtainable is 15 and the maximum score obtainable is 105. This is then divided by 15 to obtain the minimum overall CeD-GSRS score of 1 and maximum of 7. It has 3 domains- Abdominal pain, Indigestion and Diarrhea domains, each domain having a score ranging from 1-7. The higher the overall score, the more severe the symptoms. | Median | Full Range | units on a scale |
|
| Baseline Celiac Symptom Index (CSI) | Celiac Symptom Index: scores range from 16 to 80, with greater scores indicating worse symptoms | Median | Full Range | units on a scale |
|
| Baseline abdominal pain on Celiac Disease Gastrointestinal Symptom Response Scale (CeD-GSRS) | Celiac Disease Gastrointestinal Symptom Response Scale:scores range from 1 to 7, with greater scores indicating worse symptoms. On the domain of abdominal pain the minimum score is 1 and the maximum is 7. The higher the overall score, the more severe the symptoms. | Median | Full Range | units on a scale |
|
| Baseline Celiac Disease Adherence Test | Celiac Dietary Adherence Test:scores range from 5 to 35, with greater scores indicating poorer adherence; | Median | Full Range | units on a scale |
|
| Baseline IgA anti-human tissue transglutaminase assay (tTG-IgA) | IgA anti-human tissue transglutaminase assay (Inova Diagnostics, Inc., San Diego, USA): negative <20, borderline 20-30, positive >30; | Median | Full Range | unit/liter |
|
| Baseline Fecal elastase-1 levels | Normal range of fecal elastase-1 (Joli Diagnostics, Inc., Buffalo, USA): 200-500 µg/g stool,<200 µg/g stool indicates positive fecal elastase-1 test. | Count of Participants | Participants | No |
|
| OG000 | Placebo Treatment | Participants ingested placebo tablets 6 times daily (with meals and 3 snacks) for 10 days. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered |
| OG001 | PES Treatment | PES treatment was taken 6 times daily with gluten-free meals and 3 snacks. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered. |
| OG002 | Within Participant Difference in Scores Between Treatment Periods | We calculated a delta change between the GSRS scores at end of Placebo treatment and end of PES treatment |
|
|
|
| Secondary | Correlation of Baseline Fecal Elastase and Celiac Disease Gastrointestinal Symptom Response at End of PES Treatment | Baseline fecal elastase measurement will be correlated with Celiac Disease Gastrointestinal Symptom Rating Scale (CeD-GSRS) scores at the end of PES treatment period. Celiac Disease Gastrointestinal Symptom Response Scale:scores range from 1 to 7, with greater scores indicating worse symptoms. The minimum score obtainable is 15 and the maximum score obtainable is 105. This is then divided by 15 to obtain the minimum overall CeD-GSRS score of 1 and maximum of 7. It has 3 domains- Abdominal pain, Indigestion and Diarrhea domains, each domain having a score ranging from 1-7. The higher the overall score, the more severe the symptoms. | At the baseline visit, all subjects had their fecal elastase measured from a baseline stool sample. This fecal elastase level was then correlated at the end of the study with a participant's response to treatment. PES treatment response was measured by GSRS scores at the end of PES treatment period. | Posted | Number | 95% Confidence Interval | Correlation coefficient | Baseline visit (fecal elastase levels measured) and end of PES treatment period (CeD-GSRS scores measured) |
|
|
|
|
| Secondary | Change in Celiac Symptom Index Scores | The average per individual subject on-treatment scores in the Celiac Symptom Index (CSI) comparing PES treatment to placebo. For the Celiac Symptom Index: scores range from 16 to 80, with greater scores indicating worse symptoms Leffler DA, Dennis M, Edwards George J, Jamma S, Cook EF, Schuppan D, Kelly CP. A validated disease-specific symptom index for adults with celiac disease. Clin Gastroenterol Hepatol. 2009;7:1328-34. PubMed PMID: 19665584. | Posted | Mean | Standard Deviation | score on a scale | Measured at the end of each 10-day treatment period |
|
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | PES Treatment | Participants ingested PES tablets 6 times daily (with meals and 3 snacks) for 10 days. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered. | 0 | 12 | 0 | 12 | 0 | 12 |
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| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D045762 |
| Enzymes and Coenzymes |
| D010184 | Pancreatic Extracts |
| D014020 | Tissue Extracts |
| D045424 | Complex Mixtures |
| D006026 | Glycoside Hydrolases |