Celiac Disease
Conditions
Keywords
pancreatic enzyme supplementation
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.
Interventions
DRUGpancrelipase
Sponsors
Actavis Inc.
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Biopsy proven celiac disease. * Age 18-80. * Ongoing symptoms defined as a CeD-GSRS score of greater than 3 during the run in period. * Subject must be following a gluten free diet. * tTG \< 40 units at screening.
Exclusion criteria
* Taking prescription or over the counter enzyme supplements for 1 month prior to enrollment. * Pregnant, breastfeeding or planning pregnancy. Woman using acceptable methods of contraception will be included. Acceptable methods of contraception include oral hormonal contraceptives, implanted hormonal contraceptives, diaphragm with spermicide, condoms, intra-uterine device, abstinence, and male partner vasectomy. * Patients with a pork allergy or who are unwilling to consume pork products. * English proficiency unsuitable for completion of surveys. * Known severe pancreatic disease. * Known history of prior cancer (except squamous or basal cell skin cancer). * Patients with lactose intolerance who are unable to tolerate a minimum of 1oz (2 tablespoons) of whole milk per day. * Clinically significant abnormality in safety lab values (i.e. CBC and BMP) at screening that may impact subject safety or the scientific integrity of the study. * Other known active GI condition including but not limited to inflammatory bowel disease, small intestine bacterial overgrowth, and obvious FODMAP intolerance. * History of all major gastrointestinal surgery other than appendectomy or cholecystectomy. * Comorbid condition that in the opinion of the investigator would interfere with the subject's participation in the study or would confound the results of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Gastrointestinal Symptoms | Measured at end of each 10- day treatment period | The average per individual subject on-treatment score in the Celiac Disease Gastrointestinal Symptom Rating Scale (CeD GSRS) domains of Diarrhea, Indigestion, and Abdominal pain comparing active treatment to placebo (i.e. a paired comparison of CeD GSRS on treatment versus on placebo for each subject). CeD-GSRS: Each individual sub-section of the 15 sub-sections scores from 1 to 7, with greater scores indicating worse symptoms. A total score can range from 15 -105. This is then divided by 15 to obtain the minimum overall CeD-GSRS score of 1 and maximum of 7. It has 3 domains- Abdominal pain, Indigestion and Diarrhea domains, each domain having a score ranging from 1-7. The higher the overall score, the more severe the symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of Baseline Fecal Elastase and Celiac Disease Gastrointestinal Symptom Response at End of PES Treatment | Baseline visit (fecal elastase levels measured) and end of PES treatment period (CeD-GSRS scores measured) | Baseline fecal elastase measurement will be correlated with Celiac Disease Gastrointestinal Symptom Rating Scale (CeD-GSRS) scores at the end of PES treatment period. Celiac Disease Gastrointestinal Symptom Response Scale:scores range from 1 to 7, with greater scores indicating worse symptoms. The minimum score obtainable is 15 and the maximum score obtainable is 105. This is then divided by 15 to obtain the minimum overall CeD-GSRS score of 1 and maximum of 7. It has 3 domains- Abdominal pain, Indigestion and Diarrhea domains, each domain having a score ranging from 1-7. The higher the overall score, the more severe the symptoms. |
| Change in Celiac Symptom Index Scores | Measured at the end of each 10-day treatment period | The average per individual subject on-treatment scores in the Celiac Symptom Index (CSI) comparing PES treatment to placebo. For the Celiac Symptom Index: scores range from 16 to 80, with greater scores indicating worse symptoms Leffler DA, Dennis M, Edwards George J, Jamma S, Cook EF, Schuppan D, Kelly CP. A validated disease-specific symptom index for adults with celiac disease. Clin Gastroenterol Hepatol. 2009;7:1328-34. PubMed PMID: 19665584. |
Countries
United States
Participant flow
Recruitment details
Patients were screened for eligibility between 4/16/2015 and 5/28/2017 at Beth Israel Deaconess Medical Center in Boston Massachusetts
Pre-assignment details
21 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| All Study Treatments The treatment phase was comprised of two 10-day treatment periods. The study began with a 7 day washout period followed by Treatment period 1. After 10 day treatment period one all participants received a 7 day washout run-in period. Finally, all patients received a 10 day treatment period 2. Participants were randomized to two groups which were PES, then Placebo (n=3) or Placebo, then PES (n=9). Per cross-over design, all subjects have received both intervention at the end of the trial. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Run-in Washout Period #1 (7 Days) | Sponsor terminated study prematurely | 7 | 2 |
Baseline characteristics
| Characteristic | All Study Treatments |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Age, Continuous | 42 years |
| Baseline abdominal pain on Celiac Disease Gastrointestinal Symptom Response Scale (CeD-GSRS) | 2.8 units on a scale |
| Baseline Celiac Disease Adherence Test | 13 units on a scale |
| Baseline Celiac Disease Gastrointestinal Symptom (CeD-GSRS)Response Scale | 3.25 units on a scale |
| Baseline Celiac Symptom Index (CSI) | 35 units on a scale |
| Baseline Fecal elastase-1 levels 200-500 µg/g | 5 Participants |
| Baseline Fecal elastase-1 levels <200 µg/g | 1 Participants |
| Baseline Fecal elastase-1 levels >500 µg/g | 6 Participants |
| Baseline IgA anti-human tissue transglutaminase assay (tTG-IgA) | 12 unit/liter |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Change of Gastrointestinal Symptoms
The average per individual subject on-treatment score in the Celiac Disease Gastrointestinal Symptom Rating Scale (CeD GSRS) domains of Diarrhea, Indigestion, and Abdominal pain comparing active treatment to placebo (i.e. a paired comparison of CeD GSRS on treatment versus on placebo for each subject). CeD-GSRS: Each individual sub-section of the 15 sub-sections scores from 1 to 7, with greater scores indicating worse symptoms. A total score can range from 15 -105. This is then divided by 15 to obtain the minimum overall CeD-GSRS score of 1 and maximum of 7. It has 3 domains- Abdominal pain, Indigestion and Diarrhea domains, each domain having a score ranging from 1-7. The higher the overall score, the more severe the symptoms.
Time frame: Measured at end of each 10- day treatment period
Population: All participants who completed entire study duration were included in the analysis. A comparison of the within-pair differences (delta) in symptom scores after Pancreatic Enzyme Supplement and Placebo treatment, by the Wilcoxon signed rank test.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Treatment | Change of Gastrointestinal Symptoms | GSRS score | 35.75 units on a scale | Standard Deviation 12.11 |
| Placebo Treatment | Change of Gastrointestinal Symptoms | GSRS score: Abdominal pain | 2.5 units on a scale | Standard Deviation 1.16 |
| Placebo Treatment | Change of Gastrointestinal Symptoms | GSRS score: Diarrhea score | 1.25 units on a scale | Standard Deviation 0.45 |
| Placebo Treatment | Change of Gastrointestinal Symptoms | GSRS score: Indigestion score | 2.45 units on a scale | Standard Deviation 2.07 |
| PES Treatment | Change of Gastrointestinal Symptoms | GSRS score: Indigestion score | 2.5 units on a scale | Standard Deviation 2.07 |
| PES Treatment | Change of Gastrointestinal Symptoms | GSRS score | 37.5 units on a scale | Standard Deviation 13.38 |
| PES Treatment | Change of Gastrointestinal Symptoms | GSRS score: Diarrhea score | 1.58 units on a scale | Standard Deviation 0.9 |
| PES Treatment | Change of Gastrointestinal Symptoms | GSRS score: Abdominal pain | 2.42 units on a scale | Standard Deviation 1.16 |
| Within Participant Difference in Scores Between Treatment Periods | Change of Gastrointestinal Symptoms | GSRS score: Indigestion score | -0.18 units on a scale | Standard Deviation 2.04 |
| Within Participant Difference in Scores Between Treatment Periods | Change of Gastrointestinal Symptoms | GSRS score: Abdominal pain | 0.08 units on a scale | Standard Deviation 0.79 |
| Within Participant Difference in Scores Between Treatment Periods | Change of Gastrointestinal Symptoms | GSRS score: Diarrhea score | -0.33 units on a scale | Standard Deviation 0.65 |
| Within Participant Difference in Scores Between Treatment Periods | Change of Gastrointestinal Symptoms | GSRS score | -1.75 units on a scale | Standard Deviation 5.83 |
p-value: 0.271Wilcoxon (Mann-Whitney)
Secondary
Change in Celiac Symptom Index Scores
The average per individual subject on-treatment scores in the Celiac Symptom Index (CSI) comparing PES treatment to placebo. For the Celiac Symptom Index: scores range from 16 to 80, with greater scores indicating worse symptoms Leffler DA, Dennis M, Edwards George J, Jamma S, Cook EF, Schuppan D, Kelly CP. A validated disease-specific symptom index for adults with celiac disease. Clin Gastroenterol Hepatol. 2009;7:1328-34. PubMed PMID: 19665584.
Time frame: Measured at the end of each 10-day treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Treatment | Change in Celiac Symptom Index Scores | 36.75 score on a scale | Standard Deviation 11.62 |
| PES Treatment | Change in Celiac Symptom Index Scores | 35.92 score on a scale | Standard Deviation 9.55 |
| Within Participant Difference in Scores Between Treatment Periods | Change in Celiac Symptom Index Scores | 0.83 score on a scale | Standard Deviation 4.67 |
p-value: 0.08Linear Mixed Effects model
Secondary
Correlation of Baseline Fecal Elastase and Celiac Disease Gastrointestinal Symptom Response at End of PES Treatment
Baseline fecal elastase measurement will be correlated with Celiac Disease Gastrointestinal Symptom Rating Scale (CeD-GSRS) scores at the end of PES treatment period. Celiac Disease Gastrointestinal Symptom Response Scale:scores range from 1 to 7, with greater scores indicating worse symptoms. The minimum score obtainable is 15 and the maximum score obtainable is 105. This is then divided by 15 to obtain the minimum overall CeD-GSRS score of 1 and maximum of 7. It has 3 domains- Abdominal pain, Indigestion and Diarrhea domains, each domain having a score ranging from 1-7. The higher the overall score, the more severe the symptoms.
Time frame: Baseline visit (fecal elastase levels measured) and end of PES treatment period (CeD-GSRS scores measured)
Population: At the baseline visit, all subjects had their fecal elastase measured from a baseline stool sample. This fecal elastase level was then correlated at the end of the study with a participant's response to treatment. PES treatment response was measured by GSRS scores at the end of PES treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Treatment | Correlation of Baseline Fecal Elastase and Celiac Disease Gastrointestinal Symptom Response at End of PES Treatment | 0.223 Correlation coefficient |
p-value: 0.995Spearman rank coefficient