Celiac DiseasePhase 4NCT02475369

Pancreatic Enzyme Supplementation for Celiac Disease

A Phase 4 study testing pancrelipase in people with Celiac Disease, run by Beth Israel Deaconess Medical Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Celiac Disease
What is being tested?: pancrelipase
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 21 participants
Where: 1 siteUnited States
Study dates: May 2015to Dec 2019
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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).

Show all 11Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215

Other trials in United States

About this study

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

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.

Conditions: Celiac Disease
Being tested: pancrelipase
Keywords: pancreatic enzyme supplementation
Medical subject headings: Celiac Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

pancrelipaseDrug
Also called Viokase, lipase, protease, amylase

Study groups in NCT02475369
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: pancrelipase

What is being measured

The primary outcome is the main question the study is designed to answer.

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: 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 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.
Measured: 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: Measured at the end of each 10-day treatment period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2015Dec 2019

First posted18 Jun 2015 (estimated)
Study startMay 2015
Primary completionJun 2019
Study completionDec 2019

Why it stopped: The trial was terminated prematurely by the sponsor for administrative reasons.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Celiac DiseaseStudies of the same condition, open and under way.
More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02475369
Sponsor's protocol ID: 2014P000375
Status last verified: Apr 2021
First submitted: 16 Jun 2015
Last updated: 12 May 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 23163616
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.
PubMed 3123181
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.
PubMed 36687454

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Celiac Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 12 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pilot Study of the Efficacy of Pancreatic Enzyme Supplementation for Symptom Control in Celiac Disease Not Responding to the Gluten Free Diet
ClinicalTrials.gov ID: NCT02475369
Acronym / sponsor ID: 2014P000375
Conditions: Celiac Disease
Keywords: pancreatic enzyme supplementation
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: The trial was terminated prematurely by the sponsor for administrative reasons.
Enrolment: 21 participants (actual)
Lead sponsor: Beth Israel Deaconess Medical CenterUniversity, hospital or other
Collaborators: Actavis Inc.
Study start: May 2015
Primary completion: Jun 2019 (actual)
Study completion: Dec 2019 (actual)
First posted: 18 Jun 2015 (estimated)
Results: Posted 8 Feb 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
PES, Then Placebo	Other	Drug: pancrelipaseParticipants 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	Drug: pancrelipaseParticipants 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.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (11 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
pancrelipaseAlso: Viokase, lipase, protease, amylase	Drug	PES, Then Placebo, Placebo, Then PES

Primary outcome

Change of Gastrointestinal Symptoms
Time frame: Measured at end of each 10- day treatment period
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.

2 secondary outcomes

Correlation of Baseline Fecal Elastase and Celiac Disease Gastrointestinal Symptom Response at End of PES Treatment
Time frame: Baseline visit (fecal elastase levels measured) and end of PES treatment period (CeD-GSRS scores measured)
Change in Celiac Symptom Index Scores
Time frame: Measured at the end of each 10-day treatment period

Results and safety

Results posted to the registry on 8 Feb 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PES, Then Placebo	10	3
Placebo, Then PES	11	9

Primary outcome: Change of Gastrointestinal Symptoms

Time frame: Measured at end of each 10- day treatment period. Mean (Standard Deviation). Unit: units on a scale

Measure	Placebo Treatment n = 12	PES Treatment n = 12	Within Participant Difference in Scores Between Treatment Periods n = 12
GSRS score	35.75 (12.11)	37.5 (13.38)	-1.75 (5.83)
GSRS score: Abdominal pain	2.5 (1.16)	2.42 (1.16)	0.08 (0.79)
GSRS score: Diarrhea score	1.25 (0.45)	1.58 (0.90)	-0.33 (0.65)
GSRS score: Indigestion score	2.45 (2.07)	2.5 (2.07)	-0.18 (2.04)

Placebo Treatment vs PES Treatment: p = 0.271, Wilcoxon (Mann-Whitney)

Population analysed: 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.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Patients were followed for 34 days which was the entire duration of the study.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo Treatment	0 of 12 (0%)	0 of 12 (0%)	0 of 12
PES Treatment	0 of 12 (0%)	0 of 12 (0%)	0 of 12

Limitations and caveats (from the sponsor): Early termination by the sponsor leading to a small number of subjects analyzed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 23163616Kelly 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.
Background: PubMed 3123181Svedlund 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.
Derived from this study: PubMed 36687454Yoosuf 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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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ciaran Kelly, MD principal investigator

Beth Israel Deaconess Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing pancrelipase in people with Celiac Disease, run by Beth Israel Deaconess Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of Gastrointestinal Symptoms (time frame: Measured at end of each 10- day treatment period). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02475369, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2021.