Pancreatic Enzyme Supplementation for Celiac Disease

Study Overview
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Brief Summary
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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: Evaluate the efficacy of pancreatic enzyme supplementation for reduction of gastrointestinal symptoms in patients with celiac disease on a gluten free diet. Assess the ability of fecal elastase levels to predict response to pancreatic enzyme supplementation in patients with celiac disease on a gluten free diet.

Official Title
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Pilot Study of the Efficacy of Pancreatic Enzyme Supplementation for Symptom Control in Celiac Disease Not Responding to the Gluten Free Diet

Conditions
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Celiac Disease

Intervention / Treatment
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* Drug: pancrelipase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven celiac disease. Age 18-80. Ongoing symptoms defined as a CeD-GSRS score of greater than 3 during the run in period. Subject must be following a gluten free diet. tTG < 40 units at screening. Exclusion Criteria: Taking prescription or over the counter enzyme supplements for 1 month prior to enrollment. Pregnant, breastfeeding or planning pregnancy. Woman using acceptable methods of contraception will be included. Acceptable methods of contraception include oral hormonal contraceptives, implanted hormonal contraceptives, diaphragm with spermicide, condoms, intra-uterine device, abstinence, and male partner vasectomy. Patients with a pork allergy or who are unwilling to consume pork products. English proficiency unsuitable for completion of surveys. Known severe pancreatic disease. Known history of prior cancer (except squamous or basal cell skin cancer). Patients with lactose intolerance who are unable to tolerate a minimum of 1oz (2 tablespoons) of whole milk per day. Clinically significant abnormality in safety lab values (i.e. CBC and BMP) at screening that may impact subject safety or the scientific integrity of the study. Other known active GI condition including but not limited to inflammatory bowel disease, small intestine bacterial overgrowth, and obvious FODMAP intolerance. History of all major gastrointestinal surgery other than appendectomy or cholecystectomy. Comorbid condition that in the opinion of the investigator would interfere with the subject's participation in the study or would confound the results of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: PES, Then Placebo<br>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. | Drug: pancrelipase<br> <br> * Other names: lipase, protease, amylase;|
| Other: Placebo, Then PES<br>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. | Drug: pancrelipase<br> <br> * Other names: lipase, protease, amylase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic enzyme supplementation