Pancreatic Enzyme Supplementation for Celiac Disease

NCT02475369 | Terminated Phase 4 Results

• 1 other identifier: 2014P000375
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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:

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

Conditions

Celiac Disease

Keywords

pancreatic enzyme supplementation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Correlation of Baseline Fecal Elastase and Celiac Disease Gastrointestinal Symptom Response at End of PES Treatment

  Baseline visit (fecal elastase levels measured) and end of PES treatment period (CeD-GSRS scores measured)

• Change in Celiac Symptom Index Scores

  Measured at the end of each 10-day treatment period

Study Arms (2)

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.

Drug: pancrelipase

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.

Drug: pancrelipase

Interventions

pancrelipase DRUG

Also known as: Viokase, lipase, protease, amylase

PES, Then Placebo; Placebo, Then PES

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Actavis Inc.: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (3)

• 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.

  PMID: 23163616 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.

  PMID: 3123181 BACKGROUND

• 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.

  PMID: 36687454 DERIVED

MeSH Terms

Conditions

Celiac Disease

Interventions

Pancrelipase; Lipase; Peptide Hydrolases; Amylases

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Carboxylic Ester Hydrolases; Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes; Pancreatic Extracts; Tissue Extracts; Complex Mixtures; Glycoside Hydrolases

Limitations and Caveats

Early termination by the sponsor leading to a small number of subjects analyzed.

Results Point of Contact

• Title: Caitlin Barrett
• Organization: BIDMC

cbarret5@bidmc.harvard.edu

617-667-8266

Study Officials

• Ciaran Kelly, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 16, 2015
• First Posted: June 18, 2015
• Study Start: May 1, 2015
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2019
• Last Updated: May 12, 2021
• Results First Posted: February 8, 2021

Record last verified: 2021-04

Locations

US (1)