Trial Outcomes & Findings for Pancreatic Enzyme Supplementation for Celiac Disease (NCT NCT02475369)

Last Updated: 2021-05-12

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

21 participants

Primary outcome timeframe

Measured at end of each 10- day treatment period

Results posted on

2021-05-12

Participant Flow

Patients were screened for eligibility between 4/16/2015 and 5/28/2017 at Beth Israel Deaconess Medical Center in Boston Massachusetts

21 participants were randomized.

Participant milestones

Participant milestones
Measure	PES, Then Placebo 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.	Placebo, Then PES 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.
Run-in Washout Period #1 (7 Days) STARTED	10	11
Run-in Washout Period #1 (7 Days) COMPLETED	3	9
Run-in Washout Period #1 (7 Days) NOT COMPLETED	7	2
Treatment Period #1 (10 Days) STARTED	3	9
Treatment Period #1 (10 Days) COMPLETED	3	9
Treatment Period #1 (10 Days) NOT COMPLETED	0	0
Run-in Washout Period #2 (7 Days) STARTED	3	9
Run-in Washout Period #2 (7 Days) COMPLETED	3	9
Run-in Washout Period #2 (7 Days) NOT COMPLETED	0	0
Treatment Period #2 (10 Days) STARTED	3	9
Treatment Period #2 (10 Days) COMPLETED	3	9
Treatment Period #2 (10 Days) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	PES, Then Placebo 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.	Placebo, Then PES 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.
Run-in Washout Period #1 (7 Days) Sponsor terminated study prematurely	7	2

Baseline Characteristics

Pancreatic Enzyme Supplementation for Celiac Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Treatments n=12 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	42 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants
Baseline Celiac Disease Gastrointestinal Symptom (CeD-GSRS)Response Scale	3.25 units on a scale n=5 Participants
Baseline Celiac Symptom Index (CSI)	35 units on a scale n=5 Participants
Baseline abdominal pain on Celiac Disease Gastrointestinal Symptom Response Scale (CeD-GSRS)	2.8 units on a scale n=5 Participants
Baseline Celiac Disease Adherence Test	13 units on a scale n=5 Participants
Baseline IgA anti-human tissue transglutaminase assay (tTG-IgA)	12 unit/liter n=5 Participants
Baseline Fecal elastase-1 levels <200 µg/g	1 Participants n=5 Participants
Baseline Fecal elastase-1 levels 200-500 µg/g	5 Participants n=5 Participants
Baseline Fecal elastase-1 levels >500 µg/g	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Treatment n=12 Participants Participants ingested placebo tablets 6 times daily (with meals and 3 snacks) for 10 days. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered	PES Treatment n=12 Participants PES treatment was taken 6 times daily with gluten-free meals and 3 snacks. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered.	Within Participant Difference in Scores Between Treatment Periods n=12 Participants We calculated a delta change between the GSRS scores at end of Placebo treatment and end of PES treatment
Change of Gastrointestinal Symptoms GSRS score	35.75 units on a scale Standard Deviation 12.11	37.5 units on a scale Standard Deviation 13.38	-1.75 units on a scale Standard Deviation 5.83
Change of Gastrointestinal Symptoms GSRS score: Abdominal pain	2.5 units on a scale Standard Deviation 1.16	2.42 units on a scale Standard Deviation 1.16	0.08 units on a scale Standard Deviation 0.79
Change of Gastrointestinal Symptoms GSRS score: Diarrhea score	1.25 units on a scale Standard Deviation 0.45	1.58 units on a scale Standard Deviation 0.90	-0.33 units on a scale Standard Deviation 0.65
Change of Gastrointestinal Symptoms GSRS score: Indigestion score	2.45 units on a scale Standard Deviation 2.07	2.5 units on a scale Standard Deviation 2.07	-0.18 units on a scale Standard Deviation 2.04

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo Treatment n=12 Participants Participants ingested placebo tablets 6 times daily (with meals and 3 snacks) for 10 days. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered	PES Treatment PES treatment was taken 6 times daily with gluten-free meals and 3 snacks. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered.	Within Participant Difference in Scores Between Treatment Periods We calculated a delta change between the GSRS scores at end of Placebo treatment and end of PES treatment
Correlation of Baseline Fecal Elastase and Celiac Disease Gastrointestinal Symptom Response at End of PES Treatment	0.223 Correlation coefficient Interval -0.198 to 0.646	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Treatment n=12 Participants Participants ingested placebo tablets 6 times daily (with meals and 3 snacks) for 10 days. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered	PES Treatment n=12 Participants PES treatment was taken 6 times daily with gluten-free meals and 3 snacks. To facilitate duodenal digestion Omeprazole (20 mg/QD) was co-administered.	Within Participant Difference in Scores Between Treatment Periods n=12 Participants We calculated a delta change between the GSRS scores at end of Placebo treatment and end of PES treatment
Change in Celiac Symptom Index Scores	36.75 score on a scale Standard Deviation 11.62	35.92 score on a scale Standard Deviation 9.55	0.83 score on a scale Standard Deviation 4.67

Adverse Events

Placebo Treatment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

PES Treatment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Caitlin Barrett

BIDMC

Phone: 617-667-8266

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place