Clinical trial NCT02475369
Conditions: Celiac Disease
Keywords: pancreatic enzyme supplementation
Sponsor: Beth Israel Deaconess Medical Center
Start date: 2015-05-01; Completion date: 2019-12-01
Enrollment: 21 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

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. Evaluate the efficacy of pancreatic enzyme supplementation for reduction of gastrointestinal symptoms in patients with celiac disease on a gluten free diet.
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.

Detailed description:

Arms: arm 1: 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. arm 2: 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.
Interventions: intervention 1: pancrelipase
Intervention descriptions: intervention 1: None

Protocol documents:
Prot_SAP_000.pdf: 
 
Pancreatic Enzyme 
Supplementation for Celiac 
Disease 
NCT: 02475369 
 
 
8/8/2017 
 
 


(CCI) Committee on Clinical Investigations 
Page 1 of 14 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 08Aug2017 
 
 
PART B 
STUDY DESCRIPTION 
 
TITLE OF PROTOCOL 
Pilot Study of the efficacy of pancreatic enzyme supplementation 
for symptom control in celiac disease not responding to the gluten 
free diet 
Principal Investigator 
Ciaran P Kelly, MD 
 
B1. 
PURPOSE OF PROTOCOL 
 
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) Evaluate the efficacy of pancreatic enzyme supplementation for reduction of gastrointestinal 
symptoms in patients with celiac disease on a gluten free diet.  
(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. 
 
 
 
B2. 
SIGNIFICANCE AND BACKGROUND FOR THE STUDY 
 
Celiac disease is a systemic immunological disorder in which the sentinel lesion is an enteropathy 
triggered by ingestion of prolamine-rich, cereal protein-derived, polypeptides collectively called 
“gluten” including proteins from wheat (gliadin), rye (secalin) and barley (hordein).1,2  Ingestion of the 
offending proteins leads to intestinal inflammation and mucosal damage, which frequently results in a 
spectrum of gastrointestinal symptoms, increased intestinal permeability, maldigestion and 
malabsorption, occult gastrointestinal bleeding, diarrhea and systemic manifestations including 
malignancy, osteoporosis, fertility abnormalities and autoimmune disease.1-3 
 
Celiac disease is unique among chronic, auto-immune inflammatory disorders as both instigating 
antigen and end-organ pathology are well defined.4,5  The elucidation of the gluten proteins as the 
offending agent in celiac disease6 has allowed for highly efficient in vitro and in vivo investigations 
that have identified what are currently accepted to be the three pivotal steps in celiac disease 
activation.  First, intact gluten peptides are delivered to the small intestinal mucosa.7 Second, gluten 
peptides are selectively deamidated in the extracellular matrix of the intestinal submucosa.8 Finally, 
deamidated gluten peptides bind to HLA DQ2 or HLA DQ8 on antigen presenting cells activating both 
cell mediated and humoral immunity.9,10   
 
Understanding of this pathway has markedly advanced clinical practice, most clearly though allowing 
development of a simple and accurate serologic test in the form of antibody to tissue 
transglutaminase (tTG).11  Using serological assays, the prevalence of celiac disease in the United 
States and Europe ranges between 1:250 and 1:67.12  A growing body of literature supports the 
conclusion that celiac disease is a common entity in diverse populations across the globe.  
 
While we have an excellent understanding of celiac disease pathophysiology,13,14 diagnosis,11 
clinical manifestations,1,2 response to gluten withdrawal15-19, and gluten challenge20,21, treatment 
of celiac disease is not significantly different now than 50 years ago.  Unfortunately, while the gluten 
free diet is safe, it is not as effective as patients or clinicians would like.  Studies currently suggest 
that up to 30% of celiac patients return to their doctor for persistent or recurrent symptoms and that a 
much larger proportion have symptoms that do not trigger medical evaluation.19,22-24  
 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 08Aug2017 
 
There are multiple reasons for persistent symptoms, but one of the etiologies that has been observed 
across multiple studies is pancreatic exocrine insufficiency.19,22,25,26  The role of pancreatic 
endocrine dysfunction as a cause of persisting or recurrent symptoms in patients with celiac disease 
already adhering to a gluten free diet is well known and repeatedly described in the clinic literature on 
celiac disease.19,27,28  A recent summary can be obtained from the 2013 ACG Clinical Guidelines: 
Diagnosis and Management of Celiac Disease.29 The abstract/summary of the guidelines states:  
“Persistent or recurring symptoms should lead to… evaluation for disorders associated with celiac 
disease that could cause persistent symptoms, such as microscopic colitis, pancreatic exocrine 
dysfunction, and complications of celiac disease, such as enteropathy-associated lymphoma or 
refractory celiac disease, should be entertained.” The importance of considering pancreatic 
insufficiency in nonresponsive celiac disease is discussed further in the text of the Guidelines but the 
discussion is based on review articles and case series.  No treatment trials are referenced reflecting 
the lack of prospective studies on this topic.  
 
Despite awareness in the celiac community of the potential for pancreatic exocrine insufficiency as a 
complication of celiac disease, there have been few prospective studies of pancreatic enzyme 
replacement in celiac disease and no studies to date that have taken place in the United States.  As 
the population with celiac disease has expanded rapidly in recent years,30 the potential for adjunctive 
therapies for celiac disease has become more apparent.  In this study, we propose to conduct a 
rigorous prospective study of the utility of pancreatic enzyme replacement in celiac disease and 
assess the ability of fecal elastase levels to predict response to therapy. 
 
Our goal is to provide adequate supplementation over the 10 day treatment period so as to maximize 
the opportunity for an evident therapeutic effect if indeed pancreatic enzyme insufficiency is 
contributing to the subjects’ symptoms.   
 
 
B3. 
DESCRIPTION OF RESEARCH PROTOCOL 
A. 
Study Design – Overview, Methods, Procedures 
 
Overview 
This is a single-center investigator initiated phase IV trial to examine the efficacy of pancreatic 
enzyme supplementation in individuals with celiac disease who suffer persistent symptoms 
despite a gluten free diet. 
 
Hypothesis 
Pancreatic enzyme supplementation will improve symptoms in individuals with celiac disease who 
suffer persistent symptoms despite a gluten free diet.  
 
Specific Aims: 
Specific Aim 1: Evaluate the efficacy of pancreatic enzyme supplementation for reduction of 
gastrointestinal symptoms in patients with celiac disease on a gluten free diet.  
Specific Aim 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. 
 
Primary Objective(s)/End Point(s): 
The primary endpoint for Specific Aim 1  will be 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 GSRRS on treatment versus on placebo for each subject).31,32  The outcome 
measures used in the study and in particular the CeD GSRS have been employed previously by 
the investigators in their published studies.31-33   


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 08Aug2017 
 
As a primary endpoint for Specific Aim 2, baseline fecal elastase measurement will be correlated 
to the average difference in on-treatment score in the CeD GSRS [active versus placebo].   
 
Secondary Objective(s)/End Point(s): 
 (1) Assessment of response to pancreatic enzyme supplementation in patients with celiac 
disease and either normal or low baseline fecal elastase levels.   
(2) Improvement in Celiac Symptom Index (CSI) with active treatment vs. placebo.  
(3) Reduction in number of total stools and loose stools (defined as a Bristol Score of 6-7) per 
week with active treatment vs. placebo.  
 
Experimental Design & Number and Description of Each Treatment Arm/Group: 
We propose a randomized, double blind, placebo-controlled, crossover trial of 40 participants 
overall.  Participants would have a 7 day placebo run in period for documentation of symptoms at 
baseline (study phase 1), followed by a 10 day treatment/placebo period (study phase 2), after 
which there would be another 7 day wash out period (study phase 3) and a final 10 day cross over 
(study phase 4) resulting in a total study duration of 34 days.   
Participants will be recruited from the Celiac Center at Beth Israel Deaconess Medical Center 
which currently has over 1900 registered patients with biopsy proven celiac disease.  Patients will 
be enrolled in the out-patient clinic and though targeted mailings and advertisements.  Males and 
Females over the age of 18 with biopsy-proven celiac disease and persisting symptoms despite 
adherence to a strict gluten free diet will be targeted19.  
Study visits would occur at screening (Visit 1), beginning of the third study phase (day 17-21, Visit 
2) and study conclusion (day 35-40, Visit 3).  Participants will regularly complete symptom 
surveys (Celiac Dietary Adherence Test [CDAT], to be administered at baseline; the CSI, to be 
administered daily; CeD-GSRS & a modified CSI, which are to be administered at the end of each 
study phase), a daily stool log (frequency and consistency), and a daily medication log.  
Participants will be contacted every 3 (±1) days after enrollment for safety and compliance 
assessments (e.g. medication, symptoms surveys, and stool log review). 
Active drug would be taken at a dose of 3 (three) 20,880 USP units of lipase; 78,300 USP units of 
protease; 78,300 USP units of amylase tablets with meals and 2 (two) 20,880 USP units of lipase; 
78,300 USP units of protease; 78,300 USP units of amylase tablets with snacks. Dosing will occur 
with meals and snacks (approximately 3 meals and 3 snacks per day). Our goal is to provide 
adequate supplementation over the 10 day treatment period so as to maximize the opportunity for 
an evident therapeutic effect if indeed pancreatic enzyme insufficiency is contributing to the 
subjects’ symptoms. Omeprazole (20mg orally once per day) will be co-prescribed all 34 days of 
study drug administration to facilitate duodenal digestion of the study drug. 
 
Duration of study Treatment (Per Subject): 
34 Days 
 
Doses per Subject per Treatment 
Pancreatic enzyme supplement dosage will be scaled according to the weight of the patient in 
OMR or by patient report.  
 
With meals patient will take the active pancreatic enzyme supplement as follows: 
 
 
59 kg and greater  
o 3   20,880 USP units of lipase; 78,300 USP units of protease; 78,300 USP units of 
amylase tablets with meals and 2   20,880 USP units of lipase; 78,300 USP units of 
protease; 78,300 USP units of amylase tablets with snacks.   
 
Total daily use = 3 x 3 and 2 x 3 = 15 units 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 08Aug2017 
 
 
Total per subject use = 150 (15 x 10 days)  
 
 
Between 53 and 58 kg  
o 2.5  20,880 USP units of lipase; 78,300 USP units of protease; 78,300 USP units of 
amylase tablets with meals and 2  20,880 USP units of lipase; 78,300 USP units of 
protease; 78,300 USP units of amylase tablets with snacks.   
 
Total daily use = 2.5 x 3 and 2 x 3 = 13.5 units 
 
Total per subject use = 135 (13.5 x 10 days)  
 
 
Between 47 and 53 kg  
o 2.5  20,880 USP units of lipase; 78,300 USP units of protease; 78,300 USP units of 
amylase tablets with meals and 1.5  20,880 USP units of lipase; 78,300 USP units 
of protease; 78,300 USP units of amylase tablets with snacks.   
 
Total daily use = 2.5 x 3 and 1.5 x 3 = 12 units 
 
Total per subject use = 120 (12 x 10 days)  
 
 
Between 40 and 46 kg  
o 2   20,880 USP units of lipase; 78,300 USP units of protease; 78,300 USP units of 
amylase tablets with meals and 1.5  20,880 USP units of lipase; 78,300 USP units 
of protease; 78,300 USP units of amylase tablets with snacks.   
 
Total daily use = 2 x 3 and 1.5 x 3 = 10.5 units 
 
Total per subject use = 105 (10.5 x 10 days)  
 
Placebo: gelatin-based capsules filled with microcrystalline cellulose will match the above dosing 
schedule. 
 
The Viokace and placebo will be encapsulated to match. However, due to their size the Viokace 
tablets must be crushed and split between two capsules. Consequently, in order to consume the 
units of Viokace per day during the active treatment phase, each subject will need to take twice as 
many capsules as units listed above. To maintain the blind, subjects will also need to consume a 
matching number of placebo capsules each day during the 7-day run-in, 7-day wash-out, and 10-
day crossover phases.  
 
Because Viokace is not enteric-coated it must be co-prescribed with a proton-pump inhibitor to 
facilitate digestion in the duodenum. Study subjects will be prescribed 20mg Omeprazole to be 
taken orally once a day before breakfast for the entire 34 days of study medication administration. 
Subjects who are already taking omeprazole or another PPI at enrollment will be allowed to 
continue taking it as prescribed with no need to discontinue or switch over the course of the study. 
 
While study subjects will be provided with the study medication and omeprazole (collectively 
referred to as “study treatment”) necessary to complete study phases 1 and 2 at visit #1, they will 
be asked to refrain from initiating study treatment until they have been notified by study staff that 
they can do so. This delay is intended to accommodate the lag in time between visit #1 and the 
receipt of screening lab results (CBC, BMP, and celiac serologies). Once these results have been 
received and reviewed by a study physician, study subjects will be called by study personnel 
notifying them of whether they can initiate study treatment. Subjects who are eligible to continue in 
the study will be instructed to begin to take the study treatment the following day. The day on 
which the subject begins the study treatment will be considered Day 1, and the timing of all 
subsequent study visits and assessments will follow accordingly as described within this protocol. 
 
Study treatment administration will be explained to subjects in detail by the study coordinator at 
Visit #1 and via a study medication instructions sheet. 
 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 08Aug2017 
 
Number and Timing of Visits/Evaluations: 
Study visits will occur at screening (Visit 1), beginning of the second study phase (day 14-21, Visit 
2) and study conclusion (day 35-40, Visit 3). Each of these visits will include medical history 
review by study personnel, a physical exam performed by a licensed study physician, and the 
collection of vital signs. Visit 1 will include a dietetic assessment to be completed with a Celiac 
Center dietician. This dietetic assessment will occur either in-person at Visit 1 following the 
consent or following Visit 1 over the phone prior to the start of the study medication. The purpose 
of this dietetic assessment is to (1) evaluate for recent gluten exposure and obvious other food 
intolerances (e.g. moderate lactose intolerance, FODMAP intolerance), and (2) educate the 
subject regarding the diet they should follow while on the study. 
At Visit 1 participants will be asked to complete the CeD-GSRS, CSI, and CDAT questionnaires. 
Following Visit 1, participants will be asked to complete the CSI once each day for the duration of 
the study period. Participants will additionally complete the CeD-GSRS and a specialized CSI that 
includes a question regarding potential gluten exposure at the end of each study phase, i.e at 
days 7, 17, 24, and 34 (please see the protocol schema on page 14 below for a depiction of the 
study phases).  
If participants do not attend Visit 2 until after study day 17 they will be instructed to stop taking 
study medication, including omeprazole if prescribed for the study, until they attend Visit 2 and 
can receive the placebo washout.  
Participants will additionally complete a daily medication log to record when they take the study 
medication and a daily paper stool log to record bowel movement frequency and consistency.  
Participants will be contacted every 3 (±1) days after enrollment for safety and compliance 
assessments (e.g. medication, symptoms survey, and stool log review).  
 
Laboratory Assessments: 
Safety outcomes will be assessed at visit 1 (screening) and 3 (study conclusion) and will include:  
 
Celiac serologies (IgA tTG and IgA/IgG DGP) 
 
Complete blood count (CBC) 
 
Basic metabolic panel (BMP) 
Fecal elastase will additionally be assessed at Visit 1. Stool sampling for fecal elastase testing will 
occur at Visit 1 when possible or a stool sample will be returned at Visit 2. 
Female subjects will be asked to provide a urine sample at Visit 1 for β-HcG pregnancy testing. 
 
Safety Evaluations:  
Safety evaluations will occur at all study visits and contacts through interview with study 
personnel, and/or physical examination, and/or symptom monitoring via the weekly surveys. 
Safety outcomes will include celiac serologies (IgA tTG and IgA/IgG DGP), CBC, and BMP on 
screening and study conclusion. 
Adverse events (AEs) will be assessed at study visits and contacts. Serious adverse events 
(SAEs) will be defined as those that: result in death; are an immediate threat to life; require 
inpatient hospitalization, or prolongation of existing hospitalization; result in persistent or 
significant disability/incapacity; and/or are a congenital anomaly or birth defect. 
For all AEs we will provide an assessment of causal relationship to the IP. Causal relationship will 
be assessed by answering the following question: Is there a reasonable possibility the IP caused 
the event? The answer to this question is “yes” if there is evidence to suggest a casual 
relationship between the drug and the adverse event (i.e. there is a reasonable temporal 
relationship, and/or the events are unlikely to be attributable to underlying disease, other drugs, or 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 08Aug2017 
 
other factors). Dechallenge and/or rechallenge (if available) is positive. The answer to this 
question is “no” if the relationship is unlikely or nonexistent (i.e. there is no reasonable temporal 
relationship and/or the events are likely to be manifestations of underlying diseases, or commonly 
occur in the study population independent of drug exposure or other drugs/factors provide 
plausible explanations for the events), or the patient did not take the investigational product. 
The Principal Investigator will inform Forest Global Drug Safety of all SAEs. Forest Global Drug 
Safety will be notified immediately regarding any SAE that occurs after informed consent is 
obtained. 
The Principal Investigator will report the event within 24 hours of first knowledge of any AE that 
meets one of the criteria for an SAE, to Forest Global Drug Safety on an SAE report form. If, 
during follow-up, any nonserious AE worsens and eventually meets the criteria for an SAE, that 
AE will be recorded as a new SAE. 
The study center will transmit the SAE report form to the SAE fax number (631) 858-7906 within 
24 hours of first awareness of the event at the study center. 
Supplemental information shall be submitted as soon as available and may include laboratory 
results, radiology reports, progress notes, hospital admission and emergency room notes, holding 
and observation notes, discharge summaries, autopsy reports, and death certificates. 
Regarding the reporting of pregnancy: Study center personnel will report every pregnancy on a 
pregnancy report form as soon as possible (within 24 hours of first awareness of the pregnancy to 
the pregnancy fax number, (631) 858-7906), even if no AE has occurred, and follow it to term. If, 
however, the pregnancy is associated with an SAE (e.g. if the mother is hospitalized for 
dehydration), in addition to the pregnancy report form, a separate SAE report form will be filed.  
All relevant SAE or pregnancy information will be faxed to the Forest Global Drug Safety Department 
at (631) 858-7906. 
 
B. 
Statistical Considerations 
Sample Size Justification:   
As this is a pilot study and the response of celiac symptoms to pancreatic enzyme 
supplementation has never been assessed, sample size is not possible to definitively calculate.  
However, based on the literature, a standard deviation of σ=0·55 is estimated and a >0.4 point 
change in CeD-GSRS can be considered clinically significant.  Allowing for a type-1 error rate of 
=0·05, and assuming a 10% drop-out rate, 32 total participants would provide 80% power to 
detect a 0·4-point difference in CeD-GSRS score between pancreatic enzyme  treatment and 
placebo using a two treatment cross over design. Allowing for drop out and treatment non-
compliance we plan to recruit until 30 participants have completed the treatment phases, up to a 
maximum of 40 eligible individuals.  While this may appear somewhat overpowered, this sample 
size is feasible and allows for what is a very high degree of uncertainty regarding both the 
possible treatment effect and the influence of fecal elastase levels on efficacy, as described 
below.   
 
Data Analysis:   
Efficacy analyses will include all patients receiving ≥1 dose of study drug during double-blind 
treatment and with ≥1 post-baseline assessment (Modified Intent-to-Treat [MITT] population). 
Baseline score will be considered the last non-missing observation before the first dose of pancreatic 
enzyme or placebo. The primary endpoint is the difference in mean CeD-GSRS score on treatment 
vs. placebo.  Mean score for each participant will be generated by averaging the daily patient 
reported outcome (CeD-GSRS and CSI) scores across the study periods, such that there will be a 
single mean score per participant for the run-in phase and each treatment phase. The mean intra-
subject score will then be averaged across the entire cohort for the relevant study phase.  
 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 08Aug2017 
 
We will use standard two-treatment cross over study analysis in which participant scores during drug 
treatment (GSRSrx) for the primary outcome are compared to participant scores on placebo 
(GSRSpcb).  Assuming the data are normally distributed, if pancreatic enzyme supplementation is 
effective we would expect GSRSrx < GSRSpcb.  The study as describe above is powered so that we 
will reach statistical significance if GSRSpcb - GSRSrx >0.4 using Student’s paired t-test p<0.05.      
 
Sensitivity analyses will be conducted using Mixed Model for Repeated Measures (MMRM). MMRM 
analyses will include treatment and study week as main effects, gender, baseline CeD-GSRS score 
as covariates, and weekly CeD-GSRS scores as repeated measures. Should data be non-normal, we 
will transform results into categorical data by calculating the proportion of patients with a >30% 
reduction in CeD-GSRS score on treatment and on placebo compared to their individual scores at 
baseline.  If treatment is effective, we would expect a significantly greater proportion of patients to 
have a minimally clinically significant difference in GSRS score on treatment compared to placebo 
which can be evaluated using the Fishers Exact Test.   
 
A primary secondary outcome will be an assessment of treatment response by fecal elastase status.  
We will assess the ability of fecal elastase levels to predict response to therapy in two separate 
analyses.  In the first, we will assess the proportion of treatment responders among individuals with 
low fecal elastase defined as levels less than 100, compared to those with fecal elastase levels 
greater than 100. This proportion will be compared using Fisher’s exact test.  Separately, as we 
cannot reliably predict the spectrum of fecal elastase levels or the degree of improvement with 
therapy we will evaluate any correlation between fecal elastase levels and change in CeD-GSRS 
scores both in univariate analysis and after controlling for demographics and relevant clinical 
variables including time on the gluten free diet.   
 
Further secondary outcomes will include mean CSI scores on treatment vs. placebo, as well as 
difference between mean run-in CeD-GSRS and CSI scores and mean scores on treatment vs. 
placebo, and the proportion of patients achieving a 50% reduction in mean abdominal pain score from 
baseline  with drug vs. placebo. Secondary endpoints will be analyzed similarly to the primary 
endpoint using Student’s T test for normally distributed continuous variables and fishers exact test for 
non-normal or categorical variables.   
 
All descriptive data, including participant demographics, will be presented as the mean and 95% 
confidence interval.  
 
All statistical tests will be analyzed with SPSS software (version 19; SPSS Software, Microsoft Corp., 
Redmond, WA, USA). A P value of .05 or less will be considered statistically significant. 
 
Safety assessments will performed for all patients who received ≥1 dose of pancreatic enzyme or 
placebo.  
 
 
 


(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 08Aug2017 
 
C. 
Subject Selection 
Inclusion Criteria: 
 
1. Biopsy proven celiac disease. 
2. Age 18-80. 
3. Ongoing symptoms defined as a CeD-GSRS score in the highest domain of 3 or greater at 
Visit 1. 
4. Subject must be following a gluten free diet. 
5. tTG < 40 units  at screening. 
  
Exclusion Criteria: 
1. Taking prescription or over the counter enzyme supplements for 1 month prior to enrollment. 
2. 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. 
3. Patients with a pork allergy or who are unwilling to consume pork products. 
4. English proficiency unsuitable for completion of surveys. 
5. Known severe pancreatic disease. 
6. Known history of prior cancer (except squamous or basal cell skin cancer). 
7. Patients with lactose intolerance who are unable to tolerate a minimum of 1oz (2 tablespoons) 
of whole milk per day. 
8. 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.   
9. Other known active GI condition including but not limited to inflammatory bowel disease, small 
intestine bacterial overgrowth, and obvious FODMAP intolerance. 
10. History of all major gastrointestinal surgery other than appendectomy or cholecystectomy. 
11. 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. 
 
  
 
 
B4. 
POSSIBLE BENEFITS 
If effective, pancreatic enzyme supplementation may improve symptoms in individuals with celiac 
disease who suffer persistent symptoms despite a gluten free diet.  
 
 
 
B5. 
POSSIBLE RISKS AND ANALYSIS OF RISK/BENEFIT RATIO 
Possible risks include those associated with the study drug and blood draw. 
 
Viokace 
Common Adverse Effects: 
 
Gastrointestinal: Diarrhea (up to 10%), Indigestion (10%) 
 
Respiratory: Cough (6% to 10%) 
 
Serious/Rare Side Effects: 
 
Gastrointestinal: Distal intestinal obstruction syndrome, Fibrosing colonopathy (Rare), 
Stricture of colon (Rare) 
 
Immunologic: Anaphylaxis, Hypersensitivity reaction 


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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 08Aug2017 
 
 
Other: Recurrent tumor, Carcinoma 
 
There is additional theoretical risk of transmission of viral disease from Viokace to the study 
participant as Viokace is sourced from porcine pancreatic tissue. This risk has been reduced by 
testing for and inactivating certain viruses during manufacturing. No cases of transmission of an 
infectious illness associated with use of porcine pancreatic products have been reported to-date.  
 
Omeprazole 
Common Adverse Effects 
 
Gastrointestinal: Abdominal pain (5.2% ), Diarrhea (3.7% ), Flatulence (2.7% ), Nausea (4% ), 
Vomiting (3.2% ) 
 
Neurologic: Headache (6.9% ) 
 
Serious/Rare Side Effects: 
 
Dermatologic: Erythema multiforme (rare), Stevens-Johnson syndrome (rare), Toxic epidermal 
necrolysis (rare) 
 
Endocrine metabolic: Hypomagnesemia (rare) 
 
Gastrointestinal: Clostridium difficile diarrhea, Pancreatitis (rare) 
 
Hematologic: Agranulocytosis (rare), Hemolytic anemia (rare) 
 
Hepatic: Hepatic encephalopathy (rare), Hepatic necrosis (rare), Liver failure (rare) 
 
Immunologic: Anaphylaxis (rare) 
 
Musculoskeletal: Fracture of bone (rare), Hip fracture (rare), Rhabdomyolysis (rare) 
 
Renal: Interstitial nephritis (rare), acute (rare) 
 
Blood Sampling  
When blood is drawn from the vein, there may be some temporary discomfort and a slight risk of local 
pain, bruising, swelling, or blockage of the vein. Rarely, fainting or nerve damage may occur. 
 
 
B6. 
RECRUITMENT AND CONSENT PROCEDURES 
Recruitment 
Potential subjects will be identified in several ways. Some may be found through OMR review of patients 
seen at the Celiac Center. Patients may be approached by a co-investigator in clinic. Our CCI approved 
research databases (2007-P-000283 and 2010-P-000006) will be examined for likely candidates. These 
will be sent a recruitment letter or email or contacted by phone. This study may also be advertised 
through local celiac support groups such as the Healthy Villi. It is expected that the only subjects for the 
established celiac disease group will be contacted by mail, email or through ads. And advertisement will 
also be placed in the Metro.  
 
Participants from prior Celiac-focused studies (2013-P-000035 and 2011-P-000335) will be contacted by 
phone sent or an email and/or a letter. This email and letter will be identical to the email and letter sent to 
other prospective participants. 
 
Before contacting patients identified from the medical records or who participated in prior studies, the 
patient’s primary gastroenterologist will be contacted for prior approval. 
 
Consent 
Whenever possible, prospective subjects will be sent a copy of the ICF to review in advance of the 
screening visit. They will have the opportunity to read the ICF and ask any questions they have 
before they decide to schedule the screening visit. At the screening visit, before any research 
activities take place, an investigator will review the entire ICF with the subject. The subject will be 
completely informed verbally of the study procedures, risks and requirements. The subject will be 


(CCI) Committee on Clinical Investigations 
Page 10 of 14 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 08Aug2017 
 
given the opportunity to read the ICF. A physician will be available to answer any questions that the 
subject has. If the subject chooses to enter the study, an MD co-investigator will obtain written 
informed consent from the subject as well as sign the consent form at that time. 
  
Subject Protection 
None of the subjects in this study should be vulnerable to coercion or undue influence.  
 
B7. 
STUDY LOCATION 
Privacy  
Patient privacy will be maintained throughout the study. It is expected that most recruitment will be 
done over the phone or email. Potential subjects will have the option of choosing a location that is 
comfortable for them before talking with the study staff on the phone.  All study visits will be in the 
CRC. Additional recruitment may occur in the GI clinic. 
 
Physical Setting 
All study visits will be take place in the CRC. Phone calls to subjects and potential subjects will be 
made from offices in the Dana, Rabb, and Stoneman buildings. 
 
B8. 
DATA SECURITY 
Electronic data will be stored in a secure folder on password protected computers in locked offices.  
Paper data will be kept in locked offices on an access card restricted floor of the hospital. 
 
B9 
Multi-Site Studies 
 
Is the BIDMC the coordinating site?       
 Yes    
 No  
 
Is the BIDMC PI the lead investigator of the multi-site study?     
 Yes    
 No  
 
 
B10 
Dissemination of Research Results 
Subjects will be thanked for their participation at the end of the study. Subjects may contact the 
investigators to ask about the research findings either during a future medical appointment or by 
contacting the PI or study coordinator. 
- REFERENCES - 
 
1. 
Leffler D. Celiac disease diagnosis and management: a 46-year-old woman with anemia. Jama 
2011;306:1582-92. 
2. 
Green PH, Cellier C. Celiac disease. N Engl J Med 2007;357:1731-43. 
3. 
Farrell RJ, Kelly CP. Celiac sprue. N Engl J Med 2002;346:180-8. 
4. 
Louka AS, Sollid LM. HLA in coeliac disease: unravelling the complex genetics of a complex 
disorder. Tissue Antigens 2003;61:105-17. 
5. 
Jabri B, Kasarda DD, Green PH. Innate and adaptive immunity: the yin and yang of celiac 
disease. Immunol Rev 2005;206:219-31. 
6. 
Dicke WK, Weijers HA, Van De Kamer JH. Coeliac disease. II. The presence in wheat of a 
factor having a deleterious effect in cases of coeliac disease. Acta Paediatr 1953;42:34-42. 


(CCI) Committee on Clinical Investigations 
Page 11 of 14 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 08Aug2017 
 
7. 
Shan L, Qiao SW, Arentz-Hansen H, et al. Identification and analysis of multivalent 
proteolytically resistant peptides from gluten: implications for celiac sprue. J Proteome Res 
2005;4:1732-41. 
8. 
Dieterich W, Ehnis T, Bauer M, et al. Identification of tissue transglutaminase as the 
autoantigen of celiac disease. Nat Med 1997;3:797-801. 
9. 
Molberg O, McAdam SN, Korner R, et al. Tissue transglutaminase selectively modifies gliadin 
peptides that are recognized by gut-derived T cells in celiac disease. Nat Med 1998;4:713-7. 
10. 
Jabri B, Sollid LM. Mechanisms of disease: immunopathogenesis of celiac disease. Nat Clin 
Pract Gastroenterol Hepatol 2006;3:516-25. 
11. 
Leffler DA, Schuppan D. Update on serologic testing in celiac disease. Am J Gastroenterol 
2010;105:2520-4. 
12. 
Tommasini A, Not T, Ventura A. Ages of celiac disease: From changing environment to 
improved diagnostics. World J Gastroenterol;17:3665-71. 
13. 
Sollid LM, Jabri B. Celiac disease and transglutaminase 2: a model for posttranslational 
modification of antigens and HLA association in the pathogenesis of autoimmune disorders. Curr Opin 
Immunol;23:732-8. 
14. 
Schuppan D, Junker Y, Barisani D. Celiac Disease: From Pathogenesis to Novel Therapies. 
Gastroenterology 2009;137:1912-33. 
15. 
Rubio-Tapia A, Rahim MW, See JA, Lahr BD, Wu TT, Murray JA. Mucosal recovery and 
mortality in adults with celiac disease after treatment with a gluten-free diet. Am J Gastroenterol 
2010;105:1412-20. 
16. 
Lanzini A, Lanzarotto F, Villanacci V, et al. Complete recovery of intestinal mucosa occurs very 
rarely in adult coeliac patients despite adherence to gluten-free diet. Aliment Pharmacol Ther 
2009;29:1299-308. 
17. 
Wahnschaffe U, Schulzke JD, Zeitz M, Ullrich R. Predictors of clinical response to gluten-free 
diet in patients diagnosed with diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol 
Hepatol 2007;5:844-50; quiz 769. 
18. 
Duerksen DR, Wilhelm-Boyles C, Parry DM. Intestinal permeability in long-term follow-up of 
patients with celiac disease on a gluten-free diet. Dig Dis Sci 2005;50:785-90. 
19. 
Leffler DA, Dennis M, Hyett B, Kelly E, Schuppan D, Kelly CP. Etiologies and predictors of 
diagnosis in nonresponsive celiac disease. Clin Gastroenterol Hepatol 2007;5:445-50. 
20. 
Rujner J, Socha J, Romanczuk W, et al. [Individual sensitivity of jejunal mucosa to small doses 
of gluten in coeliac disease ]. Wiad Lek 2002;55:554-60. 
21. 
Ansaldi N, Tavassoli K, Faussone D, Forni M, Oderda G. [Clinico-histological behavior of celiac 
patients after gluten load following the definitive diagnosis]. Pediatr Med Chir 1988;10:3-6. 
22. 
Abdulkarim AS, Burgart LJ, See J, Murray JA. Etiology of nonresponsive celiac disease: results 
of a systematic approach. Am J Gastroenterol 2002;97:2016-21. 
23. 
Dewar DH, Donnelly SC, McLaughlin SD, Johnson MW, Ellis HJ, Ciclitira PJ. Celiac disease: 
management of persistent symptoms in patients on a gluten-free diet. World J Gastroenterol 
2012;18:1348-56. 
24. 
Schuppan D, Kelly CP, Krauss N. Monitoring non-responsive patients with celiac disease. 
Gastrointest Endosc Clin N Am 2006;16:593-603. 
25. 
Leeds JS, Hopper AD, Hurlstone DP, et al. Is exocrine pancreatic insufficiency in adult coeliac 
disease a cause of persisting symptoms? Aliment Pharmacol Ther 2007;25:265-71. 
26. 
Carroccio A, Iacono G, Ippolito S, et al. Usefulness of faecal elastase-1 assay in monitoring 
pancreatic function in childhood coeliac disease. Ital J Gastroenterol Hepatol 1998;30:500-4. 
27. 
Abdallah H, Leffler D, Dennis M, Kelly CP. Refractory celiac disease. Curr Gastroenterol Rep 
2007;9:401-5. 
28. 
Rostom A, Murray JA, Kagnoff MF. American Gastroenterological Association (AGA) Institute 
technical review on the diagnosis and management of celiac disease. Gastroenterology 
2006;131:1981-2002. 


(CCI) Committee on Clinical Investigations 
Page 12 of 14 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 08Aug2017 
 
29. 
Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA, American College of G. ACG 
clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 2013;108:656-
76; quiz 77. 
30. 
Rubio-Tapia A, Ludvigsson JF, Brantner TL, Murray JA, Everhart JE. The Prevalence of Celiac 
Disease in the United States. Am J Gastroenterol 2012;107:1538-44. 
31. 
Leffler DA, Kelly CP, Abdallah HZ, et al. A randomized, double-blind study of larazotide acetate 
to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol 2012;107:1554-
62. 
32. 
Kelly CP, Green PH, Murray JA, et al. Larazotide acetate in patients with coeliac disease 
undergoing a gluten challenge: a randomised placebo-controlled study. Aliment Pharmacol Ther 
2013;37:252-62. 
33. 
Leffler DA, Dennis M, Edwards George J, et al. A validated disease-specific symptom index for 
adults with celiac disease. Clin Gastroenterol Hepatol 2009;7:1328-34, 34 e1-3. 
34. 
Leffler DA, Dennis M, Edwards George JB, Kelly CP. The interaction between eating disorders 
and celiac disease: an exploration of 10 cases. Eur J Gastroenterol Hepatol 2007;19:251-5. 
35. 
Pallav K, Leffler DA, Bennett M, et al. Open conformation tissue transglutaminase testing for 
celiac dietary assessment. Dig Liver Dis 2012;44:375-8. 
36. 
Kabbani TA, Goldberg A, Kelly CP, et al. Body mass index and the risk of obesity in coeliac 
disease treated with the gluten-free diet. Aliment Pharmacol Ther 2012;35:723-9. 
37. 
Pallav K, Leffler DA, Tariq S, et al. Noncoeliac enteropathy: the differential diagnosis of villous 
atrophy in contemporary clinical practice. Aliment Pharmacol Ther 2012;35:380-90. 
38. 
Roshan B, Leffler DA, Jamma S, et al. The incidence and clinical spectrum of refractory celiac 
disease in a north american referral center. Am J Gastroenterol 2011;106:923-8. 
39. 
Jamma S, Leffler DA, Dennis M, et al. Small intestinal release mesalamine for the treatment of 
refractory celiac disease type I. J Clin Gastroenterol 2011;45:30-3. 
40. 
Leffler DA, Dennis M, Edwards George JB, et al. A simple validated gluten-free diet adherence 
survey for adults with celiac disease. Clin Gastroenterol Hepatol 2009;7:530-6, 6 e1-2. 
41. 
Garud S, Leffler D, Dennis M, et al. Interaction between psychiatric and autoimmune disorders 
in coeliac disease patients in the Northeastern United States. Aliment Pharmacol Ther 2009;29:898-
905. 
42. 
Edwards George JB, Leffler DA, Dennis MD, Franko DL, Blom-Hoffman J, Kelly CP. 
Psychological correlates of gluten-free diet adherence in adults with celiac disease. J Clin 
Gastroenterol 2009;43:301-6. 
43. 
Leffler DA, Dennis M, Edwards George J, et al. A Validated Disease-Specific Symptom Index 
for Adults with Celiac Disease. Clin Gastroenterol Hepatol 2009. 
44. 
DA Leffler CK, BM Paterson, H Abdullah, ZH Lan, A Colatrella, J Murray. A Randomized, 
Double-Blind Study of AT-1001 for the Prevention of Celiac Disease Activation with Gluten Challenge. 
Am J Gastroenterol 2012;107:1554-62. 
45. 
Leffler DA, Edwards-George J, Dennis M, et al. Factors that influence adherence to a gluten-
free diet in adults with celiac disease. Dig Dis Sci 2008;53:1573-81. 
46. 
Leffler DA, Edwards-George J, Dennis M, et al. Factors that Influence Adherence to a Gluten-
Free Diet in Adults with Celiac Disease. Dig Dis Sci 2007. 
47. 
Leffler DA, Edwards George JB, Dennis M, Cook EF, Schuppan D, Kelly CP. A prospective 
comparative study of five measures of gluten-free diet adherence in adults with coeliac disease. 
Aliment Pharmacol Ther 2007;26:1227-35. 
48. 
Leffler DA, Kelly CP, Abdallah HZ, et al. A Randomized, Double-Blind Study of Larazotide 
Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge. Am J Gastroenterol 
2012. 
49. 
Leffler D, Schuppan D, Pallav K, et al. Kinetics of the histological, serological and symptomatic 
responses to gluten challenge in adults with coeliac disease. Gut 2012. 
50. 
Ludvigsson JF, Leffler DA, Bai JC, et al. The Oslo definitions for coeliac disease and related 
terms. Gut 2012;62:43-52. 


(CCI) Committee on Clinical Investigations 
Page 13 of 14 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 08Aug2017 
 
Protocol Appendix A 
 
 
 
 
 

ICF_001.pdf: 
[CCI] Committee on Clinical Investigations 
 
Page 1 of 20 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
**FOR CCI USE ONLY** 
Approved by the Beth Israel Deaconess Medical Center  
Committee on Clinical Investigations:  
 
Consent Approval Date:   
10/18/2017 
 
 
 
Protocol Number:  
2014P000375 
 
   
 
 
 
INFORMED CONSENT FORM TO TAKE PART IN A RESEARCH STUDY 
 
SUBJECT’S NAME:        
TITLE OF RESEARCH PROTOCOL:  Pilot Study of the efficacy of pancreatic enzyme supplementation for 
symptom control in celiac disease not responding to the gluten free diet 
PRINCIPAL INVESTIGATOR:  Ciaran P. Kelly, MD 
PROTOCOL NUMBER:  2014P000375 
 
 
INTRODUCTION: 
 This is a research study; 
 Your participation is voluntary; 
 A research study includes only people who choose to take part; 
 You may or may not benefit from participating in the study.  However, your participation 
may help others in the future as a result of knowledge gained from the research; 
 You may leave the study at any time; 
 If you choose not to take part, or if you leave the study, your decision will in no way harm 
your relationship with any member of the research team or any other individuals at Beth 
Israel Deaconess Medical Center. 
 
Please read this consent form carefully and ask the investigators or study staff to explain any words or 
information that you do not clearly understand.  Once you read this consent form and understand what 
your participation in this study will involve, you will be asked to sign this form if you wish to take part.  
You will be given a signed copy of the form to keep for your records. 
 
DISCLOSURE OF SPECIAL INTERESTS OF BIDMC AND INVESTIGATORS 
This study is being conducted by Dr. Kelly and is funded by Actavis plc.  The funding agency in this 
study, Actavis, is paying Beth Israel Deaconess Medical Center and Dr. Kelly to perform this research.  
 
 
WHOM TO CONTACT IF YOU HAVE QUESTIONS OR PROBLEMS 
If you have any questions, concerns or complaints about this research or experience any problems, 
you should contact Dr. Kelly at [617] 667-1272.  
 
 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 2 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
PURPOSE 
Celiac disease is an inherited, life-long digestive disease affecting children and adults.  When 
people with celiac disease eat gluten, there is a reaction that damages their small intestine and that 
can also harm the ability of their intestine to take in nutrients from food.  Gluten is a plant protein 
found in foods like wheat, rye, and barley. It is also found in many everyday products like some 
medicines and vitamins.  About 1 in every 100 people in the United States has celiac disease. There 
is no drug treatment or cure for celiac disease.  The only available option for people with this 
disease is to follow a strict gluten-free diet. 
 
However, for some people, following a strict gluten-free diet doesn’t help their symptoms. Up to 1 in 3 
patients with celiac disease continue to have symptoms despite following a gluten-free diet. One 
possible reason for this is poor production of enzymes by the pancreas. Enzymes are proteins that 
help chemical changes occur. The pancreas is an organ in your body that produces many molecules 
and enzymes that help you digest food. In this study we want to see whether taking a pancreatic 
enzyme supplement in addition to following a gluten-free diet will help your symptoms.  
 
The pancreatic enzyme supplement that we are using is a FDA-approved drug called Viokace. The 
Viokace used in this study is investigational.  This means that this particular investigational agent, 
Viokace, has been approved by the FDA for use in other diseases or conditions, but we do not yet 
know if it is useful or safe as a treatment for persistent symptoms in patients with Celiac Disease. In 
addition to Viokace, as a part of this study you will also be asked to take omeprazole. Omeprazole 
belongs to a group of drugs called proton pump inhibitors (PPIs). The omeprazole will help protect the 
Viokace from the acids in your stomach so that it can reach your intestines, which is where the 
Viokace becomes active.  If you are already taking omeprazole or another proton pump inhibitor at 
enrollment you will be allowed to continue taking it as prescribed with no need to discontinue or 
switch over the course of the study. 
 
Viokace contains three different enzymes that are normally produced by your pancreas. These 
enzymes are called lipase, protease, and amylase and are used by your body to break nutrients into 
smaller, easier to digest molecules. Lipase is an enzyme that helps your body digest fat. Protease is 
an enzyme that helps your body digest proteins. Amylase helps your body digest sugar.  
 
One of the enzymes that your pancreas produces is called elastase. Elastase helps your body 
digest proteins that you eat. The amount of elastase in your bowel movement (stool) tells us how 
well your pancreas is producing enzymes and other molecules involved in digestion. In this study, 
we’ll measure the amount of elastase in your stool to: 
 Get a sense of how well your pancreas is producing enzymes and other molecules. 
 See whether the amount of elastase in your stool helps predict whether the study therapy 
works. 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 3 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
This study will include people who have been diagnosed with Celiac Disease who are following a 
gluten free diet and are actively experiencing symptoms. If you choose to take part in the study, you 
will continue to follow your current diet during the trial and will receive Viokace or placebo (a dummy 
pill that looks like the study medication but doesn’t contain medication). You may also receive 
omeprazole, if you aren’t currently taking it or another PPI. Various measurements will be made 
throughout the study including looking at samples of your blood, stool, and (for women) urine. You 
will also be asked to provide answers to questions about your symptoms. 
 
STUDY PARTICIPANTS 
You have been asked to be in the study because you have celiac disease and your symptoms haven’t 
gone away despite following a gluten-free diet. 
 
Approximately 40 people will take part in this study at Beth Israel Deaconess Medical Center.  A total 
of 40 people will take part in this study at all study sites. 
 
 
DESCRIPTION OF STUDY DETAILS 
If you agree to be in this study, you will be asked to read and sign this consent form.  After you sign the 
consent form, the following things will happen: 
 
1. Randomization Procedures: 
 
In this study, you will take omeprazole (or the PPI you’re currently on) in addition to Viokace 
pills or placebo pills for a total of 34 days. At certain points during the study you will take 
Viokace pills with omeprazole/your PPI, and at other points you will take placebo pills with 
omeprazole/your PPI: 
 You will not take Viokace pills for longer than 10 days during the 34-day study 
treatment period, 
 You will not be able to tell the Viokace pills apart from the placebo pills, 
 You won’t know when you’re taking Viokace or placebo pills, 
 You won’t be able to choose when you take the Viokace or the placebo pills, 
 You will know when you’re taking omeprazole/PPI pills, and 
 If you aren’t currently on omeprazole, you won’t be able to choose whether you take 
the omeprazole. 
 
In case of an emergency we will be able to find out whether you have been taking Viokace or 
placebo. We will refer to the Viokace and placebo pills as the “study medication” throughout 
the rest of this form.  
 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 4 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
Study Medication 
You must take the study medication with major meals and snacks, with a maximum of 3 
major meals and 3 snacks per day. Here is how you will take the study medication: 
 
How much study medication you take will be based on your weight.  
 
If you weigh 59 kg or greater you will take: 
 6 pills with breakfast 
 6 pills with lunch 
 6 pills with dinner 
 4 pills with snacks; maximum of 3 snacks 
 A maximum of 30 pills in one day 
 
If you weigh between 53 kg and 58 kg you will take: 
 5 pills with breakfast 
 5 pills with lunch 
 5 pills with dinner 
 4 pills with snacks; maximum of 3 snacks 
 A maximum of 27 pills in one day 
 
If you weigh between 47 kg and 53 kg you will take: 
 5 pills with breakfast 
 5 pills with lunch 
 5 pills with dinner 
 3 pills with snacks; maximum of 3 snacks 
 A maximum of 24 pills in one day 
 
If you weigh between 40 kg and 46 kg you will take: 
 4 pills with breakfast 
 4 pills with lunch 
 4 pills with dinner 
 3 pills with snacks; maximum of 3 snacks 
 A maximum of 21 pills in one day 
 
If you take less than the maximum number of pills because you don’t eat 3 major meals and 
3 snacks, that’s ok. We just ask that you record this in your daily study medication log. 
 
You should allow at least 3 hours in-between meals, and at least 1 hour between a meal and 
a snack. Make sure that you drink water when you take your study medication. 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 5 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
Omeprazole 
If you have ALREADY been prescribed omeprazole or another PPI by your doctor you 
should continue to take it as prescribed. Do not change how you take your medication. 
 
If you have NOT ALREADY been prescribed omeprazole or anther PPI by your doctor, you 
must take the omeprazole before breakfast each day that you are in the study. Here is how 
you will take the omeprazole: 
 
 1 pill before breakfast 
 
We will ask you to track when you take the omeprazole in your daily study medication log.  
 
2. Screening Procedures:  Screening procedures are tests and procedures that will be done to 
determine if you are eligible to take part in the research study.  For this research study, the 
screening procedures include: 
 
Visit 1  – This visit should take about 2 1/2 hours. At this visit:  
 
 You will have an interview. We will ask about: 
o You: your date of birth, race and ethnicity;  
o Your medical history including diseases or medical conditions you have been 
diagnosed with, surgeries you have had, and any medications that you are currently 
taking or have taken recently. 
 
 You will have a brief physical examination.  
 
 Your vital signs (heart rate, blood pressure, temperature, and breathing rate) will be 
measured. 
 
 You will undergo a dietary assessment with a Celiac Center dietician. Note: This 
assessment will happen either in-person at study visit 1, or over the phone following your 
visit 1 but before you start your study treatment. How and when you will start the study 
treatment is described below. 
 
 You will have a blood sample (about 2 tablespoons or 30 milliliters) collected. This will be 
used to check: 
o Counts of your red, white and clotting blood cells; 
o Your kidney function, blood acid/base balance, and blood sugar level; 
o How active your Celiac Disease is. 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 6 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
 You will have a urine pregnancy test if you are a woman who is able to get pregnant. 
 
 You will also be asked to provide a sample of a bowel movement (a stool sample). If you 
can’t produce the bowel movement at Visit 1 we will ask you to collect a stool sample at 
home and bring it back at Visit 2. We will give you all of the supplies and instructions that 
you will need to do this. 
 
 We will give you a take-home Bowel Movement Diary and explain how to complete it. 
o You will use it to keep track of all of the bowel movements during the study; 
o You will bring this log to each of your visits so the study staff can review it. 
 
 We will give you a take-home Study Medication Log and explain how to complete it. 
o You will use it to keep track of when you take the omeprazole/your PPI and your 
study medication during the study; 
o You will bring this log to each of your visits so the study staff can review it. 
 
 You will complete three study questionnaires: 
 
Celiac Disease Gastrointestinal Symptom Rating Scale (CeD-GSRS) 
o 
This survey asks you to rate how uncomfortable your gastrointestinal 
symptoms have been. 
o 
It is 15 questions long. 
o 
It should take 5 minutes. 
 
Celiac Symptom Index (CSI) 
o 
This survey asks about gastrointestinal symptoms and more general 
symptoms like feeling tired or having headaches. 
o 
It is 16 questions long. 
o 
It should take 5 minutes.  
 
Celiac Dietary Adherence Test (CDAT) 
o 
This survey asks you about your general symptoms and about any 
potential recent exposures to gluten. 
o 
It is 7 questions long. 
o 
It should take 3 minutes 
 
 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 7 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
 
Study Treatment START 
If we find that you qualify for this study and if you decide that you would like to participate, 
you will be given your first batch of omeprazole and of the study medication at visit 1.  
 
You will NOT begin to take the omeprazole and study medication immediately following the 
screening visit, NOR will you begin to complete the questionnaires, bowel movement diary, 
or study medication log immediately following the screening visit. (Note that if you are 
already taking omeprazole or another PPI as prescribed by your doctor, you may continue to 
take that as prescribed following the visit 1.) 
 
Instead, we will give you a call within the few days following your screening visit to let you 
know when you can begin to take your study medication. When we call you, we will instruct 
you to begin to take your study medication the following day. On the day that you start your 
study medication you will also begin to complete your study medication log, bowel movement 
diary, and study questionnaires. The day that you begin to take your study medication and 
complete your take-home materials will be called, “Day 1.” 
 
You will receive your next batch of the study medication at study Visit 2. 
 
3. Research Procedures:  If you qualify to take part in this research study, you will undergo 
these research procedures:  
 
Visit 2 (Day 14-21) – This visit should take about 1 hour. At this visit:  
 
 If you come to Visit 2 after Day 17 we will ask you to stop taking the study medication, 
omeprazole (ONLY if you are taking it just for the study), and the questionnaires on Day 
17. We will tell you when this is. You will begin taking the medication and questionnaires 
after Visit 2.  
 
 You will return the bottles of study medication that you used up over the first half of the 
study. 
 
 You will have an interview during which we will: 
o Review your take-home questionnaires; 
o Review your Bowel Movement Diary; 
o Review your Study Medication Log; 
o Ask you about your symptoms. 
 
 You will have a brief physical examination.  
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 8 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
 
 Your vital signs (heart rate, blood pressure, temperature, and breathing rate) will be 
measured. 
 
 You will receive the second batch of study medication. 
 
 
Visit 3 (Day 35-40) – This visit should take about 1 hour. At this visit:  
 
 You will return the bottles of study medication that you used up over the second half of 
the study. 
 
 You will have an interview during which we will: 
o Review your take-home questionnaires; 
o Review your Bowel Movement Diary; 
o Review your Study Medication Log; 
o Ask you about your symptoms. 
 
 You will have a brief physical examination.  
 
 Your vital signs (heart rate, blood pressure, temperature, and breathing rate) will be 
measured. 
 
 You will have a blood sample (about 2 tablespoons or 30 milliliters) collected. This will be 
used to check: 
o Counts of your red, white and clotting blood cells; 
o Your kidney function, blood acid/base balance, and blood sugar level 
o How active your Celiac Disease is. 
 
4. Monitoring/Follow-Up Procedures.  Procedures performed to evaluate the effectiveness and 
safety of the research procedures are called “monitoring” or “follow-up” procedures.  For this 
research study, the monitoring/follow-up procedures include: 
 
Questionnaires 
 
After Visit 1, you will be asked to complete the CSI questionnaire once on each day that you 
are taking the study treatment.  
 
You will also be asked to complete the CeD-GSRS and a modified CSI 4 more times, once on 
Day 7, 17, 24 and 34.  
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 9 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
Daily Bowel Movement Diary 
 
To measure your bowel symptoms, you will also be asked to record every bowel movement 
that you have during the study.  
 You will be required to write down each bowel movement that you have over the entire 
study period.   
 You will also be asked rate each bowel movement using the Bristol Stool Form Scale 
(BSFS).  The BSFS is a 7 point picture/text reference for identifying stool form and 
consistency.  We will show you how to use the BSFS. 
 
Study Medication Log 
 
To keep track of when you take omeprazole/your PPI and your study medication we will ask 
you to complete a study medication log throughout the study.  
 You will be required to record each time that you take omeprazole/your PPI during the 
study period.   
 You will be required to record each time that you take the study medication during the 
study period.   
 
You will begin to complete the study medication log on the day that you begin taking your 
study medication (i.e. Day 1). 
 
Phone Calls 
 
You will be called by the study coordinator once every 2-4 days throughout the study. These 
phone calls will be brief and are meant to help you remember to complete your daily bowel 
movement diary and questionnaires, and to take your study medication. 
 
 
 
 
 
 
 
 
 
 
A chart with the study procedures is shown below: 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 10 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
Procedures 
Visit 1  
(Day 0) 
Visit 2 
(Day 17-21) 
Visit 3 
(Day 35-40) 
BIDMC Visit 
X 
X 
X 
Medical History 
X 
 
 
Physical Exam 
X 
X 
X 
Interview 
X 
X 
X 
Vital Signs, Height, Weight 
X 
X 
X 
Blood Draw 
X 
 
X 
Stool Test 
X 
 
 
Pregnancy Test (if necessary) 
X 
 
 
Get Study Drug 
X 
X 
 
Dietary Assessment 
X 
 
 
Complete CDAT 
X 
 
 
Complete CeD-GSRS and CSI 
X 
 
 
Complete Bowl Movement Diary daily 
X 
 
 
Complete Study Medication Log daily 
X 
 
 
Phone Contacts Every 2-4 Days 
X 
 
 
 
RISKS AND DISCOMFORTS 
As a result of your participation in this study, you are at risk for side effects listed in this section.  
You should discuss these with the investigator and with your regular doctor if you choose. 
 
Viokace 
As a participant in this study you will receive no more than 10 days of Viokace. The common, non-
serious potential side-effects associated with Viokace include: 
 Diarrhea (experienced by up to 10% of patients) 
 Indigestion (experienced by up to 10% of patients) 
 Cough (experienced by 6% to 10% of patients) 
 
Serious and rare potential side effects include: 
 Distal intestinal obstruction syndrome (rare) – This refers to when thickened stool blocks the 
intestines causing symptoms that include crampy abdominal pain, vomiting, and a palpable 
mass in the abdomen. 
 Fibrosing colonopathy (rare) – Symptoms of fibrosing colonopathy include abdominal 
pain, distension, vomiting, and constipation. Fibrosing colonopathy is rare and has been seen 
in patients on long-term, high-dose administration of Viokace. 
 Stricture of the colon (rare) – This refers to when scar tissue forms in a circle around the colon. 
As it ages and tightens the scar tissue can narrow the intestine and eventually cause blockage. 
Stricture of the colon is rare and has been seen in patients on long-term, high-dose 
administration of Viokace. 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 11 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
 Recurrence of pre-existing cancer – Patients with a prior history of cancer are excluded from 
this study. 
 Allergic reaction/anaphylaxis (rare) – Severe allergic reactions have rarely occurred in adults 
taking pancreatic enzyme supplements. Symptoms of a severe allergic reaction can include 
difficulty breathing, dizziness, rash, and itching. Please notify us or your health care provider or 
call 911 immediately if you experience any of these symptoms. 
 
Viral exposure (rare) - There is a theoretical risk that Viokace may transmit viruses to 
humans. This is because Viokace is made using pig pancreatic tissue. This risk has been 
reduced by testing for and inactivating certain viruses during manufacturing. No cases of 
transmission of an infectious illness associated with use of medical products made from pig 
pancreas have been reported to-date.  
 
It is very important that you let us know about any side effects or changes in your health that you 
experience, whether or not you think they are related to the study medication. 
 
Omeprazole 
As a participant in this study you will receive 34 days of omeprazole. The common, non-serious 
potential side-effects associated with omeprazole include: 
 Gastrointestinal:  
o Abdominal pain (experienced by at least 5.2% of patients) 
o Diarrhea (experienced by at least 3.7% of patients)  
o Flatulence (experienced by at least 2.7% of patients)  
o Nausea (experienced by at least 4% of patients)  
o Vomiting (experienced by at least 3.2% of patients) 
 Neurologic:  
o Headache (experienced by at least 6.9% of patients) 
 
Serious and rare potential side effects of omeprazole include: 
 
Skin: Erythema multiforme (skin rash with lesions), Stevens-Johnson syndrome (life 
threatening skin condition causing a painful rash), Toxic epidermal necrolysis (life threatening 
skin condition causing skin death) 
 
Hormones and Metabolsim: Hypomagnesemia (abnormally low level of magnesium in the 
blood) 
 
Digestive Tract: Clostridium difficile diarrhea (bacterial infection causing diarrhea, bloating 
and abdominal pain), Pancreatitis (inflammation of the pancreas) 
 
Blood: Agranulocytosis (decrease in white blood cells causing chronic bacterial infections), 
Hemolytic anemia (red blood cell destruction) 
 
Live: Hepatic encephalopathy (loss of brain function), Hepatic necrosis (acute liver failure), 
Liver failure  
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 12 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
 
Immune System: Anaphylaxis (severe, life threatening allergic reaction) 
 
Muscles and Skeleton: Fracture of bone, Hip fracture, Rhabdomyolysis (death of muscle 
fibers which can lead to kidney failure) 
 
Kidneys: Interstitial nephritis, acute (disorder causing swelling in kidneys) 
 
Risk of Blood Draw 
The risks and discomforts of blood drawing from a vein include the possibility of pain or bruising at 
the site of the blood draw, occasional feeling of lightheadedness, and rarely, infection at the site of 
the blood draw. 
  
Risks Associated With Surveys/Questionnaires 
Some of the questions we will ask as part of this study may make you feel uncomfortable.  You may 
refuse to answer any of the questions and you may take a break at any time during the study.  You 
may stop your participation in the study at any time. 
 
PREGNANCY 
Because of the effects of Viokace on the developing fetus is not known, you may not participate in 
this study if you are pregnant.  You will be required to take a pregnancy test to verify that you are not 
pregnant before receiving your first dose of the study medication at Visit 1. 
 
Furthermore, if you are a woman capable of becoming pregnant, you must agree to use adequate 
birth control.  For the purpose of this study, use of adequate birth control includes one of the 
following: 
 
1. oral hormonal contraceptives; 
2. implanted hormonal contraceptives  
3. diaphragm with spermicide; 
4. condoms; 
5. intra-uterine device; 
6. abstinence; 
7. male partner vasectomy. 
 
If you believe you have become pregnant while participating in this study, you must inform your 
study investigators immediately.  They will have you take a pregnancy test.  If the results 
demonstrate that you are pregnant, you must withdraw from the study, and the study investigators 
will ask to monitor your pregnancy.  To monitor your pregnancy may include (but not limited to) office 
visits, blood work, and questionnaires. 
 
 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 13 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
LOSS OF CONFIDENTIALITY 
There is the potential for loss of confidentiality by participating in this study.  Every effort will be 
made to protect the confidentiality of your identifiable information.  However, if your participation 
becomes known, it could create a problem or hardship for you depending upon the type of 
information disclosed.   
 
CONFIDENTIALITY 
Information learned from your participation in this study and from your medical record may be 
reviewed and photocopied by the Food and Drug Administration (FDA) and/or other federal and 
state regulatory agencies, and by the drug manufacturer, Actavis, accreditation agencies, the 
Committee on Clinical Investigations, the Human Subjects Protection Office and others involved in 
research administration of the Beth Israel Deaconess Medical Center with protection of 
confidentiality so far as permitted by applicable law.  Information resulting from this study and from 
your medical record may be used for research purposes and may be published; however, you will 
not be identified by name in such publications. 
 
POSSIBLE BENEFITS 
 
It is not possible to predict whether you will benefit directly from participation in this study.  However, 
your participation may help others in the future as a result of knowledge gained from the research. 
 
 
OTHER AVAILABLE OPTIONS 
Taking part in this study is voluntary.  Instead of being in this study, you have the following options: 
 
Not participating. 
 
It is important to note that it is possible to get Viokace even if you do not take part in the study. 
Viokace has not been approved by the FDA for treatment of your condition, however, many doctors 
in the community commonly prescribe the drug to treat pancreas problems.  Please be aware that 
not all doctors may agree to prescribe this drug for you, and that not all health insurance companies 
will pay for the drug when it is prescribed for celiac disease. 
 
This research study is not meant to diagnose or treat medical problems not specifically stated in this 
informed consent document.  Participation in this research study does not take the place of routine 
physical examinations or visits to your regular doctor. 
 
We recommend that you discuss these and other options with the investigator and your regular 
doctor so that you can make a well-informed decision about participating in this study. 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 14 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
FUTURE STUDIES 
Our research group will do other studies in the future that you may qualify for. We would like your 
permission to keep your name, phone number, address, and email address on file so that we can 
contact you about these studies. Please initial one of the lines below to say if you will allow us to do 
this. 
 
 
_______ Yes, please keep my name and contact information and contact me about future studies. 
 
 
_______ No, please do not contact me about future studies. 
 
Even if you say yes you can tell us any time that you don’t want to be contacted about studies any 
more. We will stop right away. 
 
 
IF YOU DECIDE NOT TO TAKE PART IN THE STUDY 
 
Participation in this study is voluntary.  You have the right to decide not to take part in this study.  If 
you choose to participate, you have the right to leave the study at any time. Your decision to not 
participate will not result in any penalties or loss of benefits to you. The investigators will tell you 
about new information that may affect your willingness to stay in this study.  
 
If you decide not to participate in the study or decide to leave the study early, your decision will not 
affect your relationship with the research team or any other individual at Beth Israel Deaconess 
Medical Center.   
 
INVESTIGATORS RIGHT TO STOP THE STUDY 
 
The investigators have the right to end your participation in this study if they determine that you no 
longer qualify to take part, or if it would be dangerous for you to continue, or if you do not follow 
study procedures as directed by the investigators.  Beth Israel Deaconess Medical Center or the 
funding source may stop the study at any time. 
 
COSTS AND/OR PAYMENTS TO YOU 
 
COSTS COVERED BY STUDY 
You will not be charged for any tests, procedures, or medications that are part of this research 
study. 
 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 15 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
PAYMENTS TO YOU: 
 
You will receive a voucher for three free hours of parking for each visit that you attend. 
 
COST OF RESEARCH RELATED INJURY: 
 
If you are injured as a direct result of your participation in this study, you should contact the 
Investigator at the number provided under the section “Who to Call if You Have Questions” in this 
form.  You will be offered the necessary care to treat your injury. We reserve the right to bill your 
insurance company or the sponsor, if appropriate, for the care you get for the injury.   We will try to 
get these costs paid for, but you may be responsible for some of them.  You may be responsible for 
all co-payments and deductibles required under your insurance.   At this time there is no plan to 
reimburse you for items such as lost wages or lost time from work.  By signing this consent form you 
have not given up any legal rights. 
 
 
A description of this clinical trial will be available on www.ClinicalTrials.gov as required by U.S. law.  
This Web site will not include information that can identify you.  At most, the Web site will include a 
summary of the results.  You can search this Web site at any time. 
 
 
AUTHORIZATION FOR USE AND DISCLOSURE OF YOUR PROTECTED HEALTH 
INFORMATION 
As part of this study, we will be collecting, using and sharing with others information about you.  
Please review this section carefully as it contains information about the federal privacy rules and the 
use and disclosure of your information.   
 
PROTECTED HEALTH INFORMATION [PHI] 
By signing this informed consent document, you are allowing the investigators and other authorized 
personnel to use [internally at BIDMC] and disclose [to people and organizations outside the BIDMC 
workforce identified in this consent] health information about you.  This may include information 
about you that already exists (for example: your medical records and other sources of health 
information, demographic information, the results of any laboratory tests, and mental health records 
if applicable as well as any new information generated as part of this study.  This is your Protected 
Health Information. 
 
PEOPLE/GROUPS AT BIDMC WHO WILL SHARE AND USE YOUR PROTECTED HEALTH INFORMATION 
Your Protected Health Information may be shared with and used by investigators working on this 
study, including the supporting research team (such as research assistants and coordinators, 
statisticians, data managers, laboratory personnel, pharmacy personnel, and administrative 
assistants), and may also be shared and used by other health care providers at BIDMC who have 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 16 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
treated you in the past and have information relevant to the research, or who provide services to you 
in connection with the research.  Your Protected Health Information may also be shared with the 
members and staff of the Committee on Clinical Investigations of Beth Israel Deaconess Medical 
Center, which is responsible for reviewing studies for the protection of the research subjects.  
 
PEOPLE/GROUPS OUTSIDE OF BIDMC WITH WHOM YOUR PROTECTED HEALTH INFORMATION WILL BE 
SHARED 
We will take care to maintain confidentiality and privacy about you and your Protected Health 
Information.  We may share your Protected Health Information with the following groups so that they 
may carry out their duties related to this study: 
 
 The funding source and/or sponsor of this study (Actavis) and, where applicable, the people 
and companies that the funding source and/or sponsor use to oversee, administer, or 
conduct the research (for example, clinical research organizations are companies that are 
sometimes hired by research sponsors to help manage and run a clinical research study) 
 The other hospitals and medical centers taking part in this study and research collaborators 
at those institutions 
 Any external health care providers who provide services to you in connection with this 
research 
 Laboratories not affiliated with BIDMC that are involved in conducting tests related to the 
research 
 Statisticians and other data monitors not affiliated with BIDMC 
 The members and staff of any other IRBs (beyond the BIDMC Committee on Clinical 
Investigations) that oversee the research  
 Centralized data collectors  
 Your health insurance company 
 The Food and Drug Administration [FDA], the Department of Health and Human Services 
[DHHS], the National Institute of Health [NIH], the Office for Human Research Protections 
[OHRP], and other federal and state agencies that may have jurisdiction over the research 
 Hospital and Clinical Research Accrediting Agencies 
 Data and Safety Monitoring boards that oversee this study (if applicable) 
 
Those who receive your Protected Health Information during the course of the research may not be 
required by the federal privacy regulations to protect it, and they may make further disclosures to 
others and use your information without being subject to penalties under those laws.   
 
 
WHY WE ARE USING AND SHARING YOUR PROTECTED HEALTH INFORMATION 
The main reason for using and sharing your Protected Health Information is to conduct and oversee 
the research as described in this Informed Consent Document.  There are many other reasons 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 17 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
beyond the research for which BIDMC may use or disclose your Protected Health Information.  Not 
all of these reasons require your express written authorization.  For example, we will use and share 
your Protected Health Information to ensure that the research meets legal, institutional and 
accreditation requirements and to conduct public health activities.  The various ways in which 
BIDMC may use and disclose your protected health information without your authorization are 
explained in a document called the Notice of Privacy Practices.  If you have not received a copy of 
BIDMC’s Notice of Privacy Practices, please ask us for one and review it before signing this form.  In 
addition to signing this document, you may also be asked to sign a BIDMC General Agreement form 
acknowledging that you have received the BIDMC Notice of Privacy Practices.   
 
NO EXPIRATION DATE – RIGHT TO WITHDRAW AUTHORIZATION 
Your authorization for the use and disclosure of your Protected Health Information in this Study shall 
never expire.  However, you may withdraw your authorization for the use and disclosure of your 
Protected Health Information at any time provided you notify the Principal Investigator in writing.  If 
you would like to take back your authorization so that your Protected Health Information can no 
longer be used in this study, please send a letter notifying the Principal Investigator of your 
withdrawal of your authorization to  
Dr. Ciaran Kelly 
330 Brookline Ave. 
Boston, MA  02215.  
 
 
Please be aware that the investigators in this study will not be required to destroy or retrieve any of 
your Protected Health Information that has already been used or disclosed before the Principal 
Investigator receives your letter, and they are permitted to continue to use and disclose your 
previously collected information as necessary to complete the research. 
 
REFUSAL TO SIGN 
Your clinical treatment may not be conditioned upon whether you sign the Authorization for 
Research. However, if you choose not to sign this informed consent document and authorization for 
the use and disclosure of your Protected Health Information, you will not be allowed to take part in 
the research study. 
 
RIGHT TO ACCESS AND COPY YOUR PHI 
If you wish to review or copy your Protected Health Information as it is made part of your medical 
record, you may do so after the completion or termination of the study by sending a letter to the 
Principal Investigator requesting a copy of your Protected Health Information.  You may not be 
allowed to inspect or copy your Protected Health Information until this study is completed or 
terminated. 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 18 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
ADDITIONAL CONTACT FOR QUESTIONS OR CONCERNS 
You may contact the Human Subjects Protection Office at [617] 975-8500 in the event that you 
would like to obtain information or to offer input about the research study.   This office is 
independent of the investigator or investigator’s research staff and can also assist with questions 
relating to your rights as a participant in research, which may include questions, concerns or 
complaints about your participation in the study. 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 19 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
THE FOLLOWING PARAGRAPHS CONTAIN SOME STANDARD INFORMATION WHICH 
GENERALLY APPLIES TO INDIVIDUALS PARTICIPATING IN A RESEARCH STUDY. 
 
CONSENT FORM FOR CLINICAL RESEARCH 
I have read the previous page[s] of the consent form and the investigator has explained the details of the 
study.  I understand that I am free to ask additional questions. 
 
If I wish additional information regarding this research and my rights as a research subject, or if I believe I 
have been harmed by this study, I may contact the Human Subjects Protection Office (HSPO). 
 
I am aware that this is a research project and that unforeseen side effects may occur. 
 
I understand that the Beth Israel Deaconess Medical Center has no formal program for compensating 
patients for medical injuries arising from this research.  Medical treatment will be provided for injuries at the 
usual charge to me or to my insurer unless payment is otherwise provided for in this consent form. 
 
I understand that participation in this study is voluntary and I may refuse to participate or may discontinue 
participation at any time without penalty, loss of benefits, or prejudice to the quality of care which I will 
receive. 
 
I acknowledge that no guarantees have been made to me regarding the results of the treatment involved in 
this study, and I consent to participate in the study and have been given a copy of this form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Subject or 
 
 
 
 
Date 
Legally Authorized Representative   
(Parent if the subject is a minor) 
 
 
 
 
 
 
 
 
 
 
 
Relationship of Legally Authorized Representative to Subject   
 
The subject has been given the opportunity to read this consent form and to ask questions before signing, and 
has been given a copy. 
 
 
___________________________________________________________ 
SIGNATURE OF INVESTIGATOR/Co-Investigator   
DATE 
 
__________________________________________________________ 
PRINT INVESTIGATOR’S/Co-Investigator’s  
NAME 
 
A signing co-investigator must be listed on the study’s approved Research Staffing Form at the time of consent. 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018


[CCI] Committee on Clinical Investigations 
Page 20 of 20 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pilot Study of the efficacy of pancreatic 
enzyme supplementation for symptom control in celiac disease not 
responding to the gluten free diet 
PRINCIPAL INVESTIGATOR'S NAME: Ciaran P. Kelly, MD 
PROTOCOL #: 2014P000375 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   10/05/2017 
 
THE FOLLOWING SECTIONS ARE NOT NEEDED FOR ALL STUDIES AND SHOULD BE 
UTILIZED AS INDICATED: 
 
If the subject is able to speak and understand English but is not able to read or write  
 
I was present during the entire oral presentation of the informed consent and witnessed the subject’s agreement to 
participate in the study. 
 
Signature of Witness:  
 
Printed Name of Witness:  
 
Date:   
 
 
If the subject is able to understand English but is not physically able to read or write or see 
 
I was present during the entire oral presentation of the informed consent and witnessed the subject’s agreement to 
participate in the study. 
 
Signature of Witness:  
 
Printed Name of Witness:  
 
Date:   
 
 
 
If the subject is not English speaking and signed the translated Short Form in lieu of the English consent 
document. 
As someone who understands both English and the language spoken by the subject, I interpreted, in the subject’s 
language, the researcher’s presentation of the English consent form.  The subject was given the opportunity to ask 
questions.  
Signature of Interpreter:  
 
Printed name of Interpreter:  
 
Date:  
 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
07/23/2018