Type 1 Diabetes
Conditions
Brief summary
Recent studies have demonstrated reduced pancreatic volume is present within months of T1D diagnosis in children, adolescents, and adults. As the pancreatic beta cells constitute only 1-2% of the pancreas, the degree of reduction in pancreas volume at disease onset suggests exocrine involvement, challenging the established paradigm of T1D being solely a disease of the endocrine pancreas. To date there has not been an investigation of the potential for pancreatic enzyme replacement therapy in the management of T1D. In individuals with cystic fibrosis-related diabetes, enzyme replacement has been shown to reduce post-prandial glycemia excursions, which are reflected in improved GLP-1 responses to mixed meal tolerance testing. As post-prandial excursions and glucose variability are a significant challenge in T1D, how enzyme replacement may impact these parameters is an important question. The investigators hypothesize that patients with T1DM who have reduced pancreatic volume will have improved glycemic responsiveness, reduced hypoglycemia, and improved symptoms of pancreatic exocrine insufficiency when treated with pancreatic enzyme replacement (CREON).
Interventions
DRUGCREON
The study will enroll 6-10 adult subjects with T1D who will receive both pancreatic enzyme replacement (CREON) or placebo each for 7 days in a random order. The effect of the intervention will be monitored by continuous glucose monitoring, diet recording, capsule counts, a mixed-meal tolerance test, and a survey to assess symptoms of PEI. This study design will allow for estimation of the effect of pancreatic enzyme replacement on the measured parameters.
DRUGPlacebo
Placebo
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants will receive CREON and placebo in a random, blinded order.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Currently receive care at the Eskind Diabetes Clinic at Vanderbilt University Medical Center * Diagnosed with T1DM for at least 12 months * Age over 18 * Total daily dose of insulin greater than 0.7u/kg/day * Current use of a continuous glucose monitor * Current use of smart phone * Able to read and speak English * Willingness and ability to download and provide CGM and pump (if applicable) data * Reduction of pancreas volume (\<0.6mL/kg body weight)
Exclusion criteria
* History of celiac disease or inflammatory bowel disease * Use of medication or supplements other than insulin to control blood glucose * Pregnancy or breast feeding * Following a restrictive diet (such as very low carb diet)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in Glucose Regulation | through study completion (4-5 weeks) | Mixed meal tolerance testing (MMTT) will be used to assess glucose regulation via c-peptide AUC at baseline, and after treatment with placebo and CREON in a random order. |
| Patient-reported Change in Pancreatic Exocrine Insufficiency (PEI) Symptoms | through study completion (4-5 weeks) | We will use the pancreatic exocrine insufficiency questionnaire (PEI-Q) to quantitate symptoms of PEI and their relative change from baseline to after treatment with placebo and Creon in a random order. Minimum score is 0, and maximum score is 4. Higher scores correlate to worse outcome, i.e., increased abdominal symptoms and bowel movement symptoms. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at Vanderbilt University Medical Center from September 2022 through March 2024. Subjects were eligible based on reduced pancreas volume as determined through their prior participation in MAP-T1D (IRB 130833).
Pre-assignment details
Eleven (11) participants were enrolled to achieve completion goal of ten (10). One subject withdrew at end of drug period A due to failed OGTT and unwillingness to continue.
Participants by arm
| Arm | Count |
|---|---|
| CREON, Then Placebo CREON is a pancreatic enzyme replacement
CREON: The study will enroll 6-10 adult subjects with T1D who will receive both pancreatic enzyme replacement (CREON) or placebo each for 7 days in a random order. The effect of the intervention will be monitored by continuous glucose monitoring, diet recording, capsule counts, a mixed-meal tolerance test, and a survey to assess symptoms of PEI. This study design will allow for estimation of the effect of pancreatic enzyme replacement on the measured parameters. | 5 |
| Placebo, Then CREON CREON is a pancreatic enzyme replacement
CREON: The study will enroll 6-10 adult subjects with T1D who will receive both pancreatic enzyme replacement (CREON) or placebo each for 7 days in a random order. The effect of the intervention will be monitored by continuous glucose monitoring, diet recording, capsule counts, a mixed-meal tolerance test, and a survey to assess symptoms of PEI. This study design will allow for estimation of the effect of pancreatic enzyme replacement on the measured parameters. | 5 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Drug Period A | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo, Then CREON | Total | CREON, Then Placebo |
|---|---|---|---|
| Age, Continuous | 22.3 years | 33.3 years | 44.2 years |
| C-peptide AUC | 24.9 ng*hr/mL | 34.4 ng*hr/mL | 44.4 ng*hr/mL |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 10 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Pancreatic exocrine insufficiency score | 0.312 units on a scale | 0.376 units on a scale | 0.44 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 10 Participants | 5 Participants |
| Region of Enrollment United States | 5 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants |
| Weight | 84.8 kg | 77.3 kg | 69.7 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Improvement in Glucose Regulation
Mixed meal tolerance testing (MMTT) will be used to assess glucose regulation via c-peptide AUC at baseline, and after treatment with placebo and CREON in a random order.
Time frame: through study completion (4-5 weeks)
Population: This analysis population is the 10 participants who completed both drug periods of the study. Five received CREON, then placebo, and the other five received placebo, then CREON.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CREON | Improvement in Glucose Regulation | End of Drug Period | 35.44 ng*hr/mL |
| CREON | Improvement in Glucose Regulation | Baseline | 34.42 ng*hr/mL |
| Placebo | Improvement in Glucose Regulation | Baseline | 34.42 ng*hr/mL |
| Placebo | Improvement in Glucose Regulation | End of Drug Period | 39.03 ng*hr/mL |
p-value: 0.43Wilcoxon (Mann-Whitney)
Primary
Patient-reported Change in Pancreatic Exocrine Insufficiency (PEI) Symptoms
We will use the pancreatic exocrine insufficiency questionnaire (PEI-Q) to quantitate symptoms of PEI and their relative change from baseline to after treatment with placebo and Creon in a random order. Minimum score is 0, and maximum score is 4. Higher scores correlate to worse outcome, i.e., increased abdominal symptoms and bowel movement symptoms.
Time frame: through study completion (4-5 weeks)
Population: This analysis population is the 10 participants who completed both drug periods of the study. Five participants received CREON, then placebo, and the other five received placebo, then CREON.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CREON | Patient-reported Change in Pancreatic Exocrine Insufficiency (PEI) Symptoms | Baseline | 0.376 score on a scale |
| CREON | Patient-reported Change in Pancreatic Exocrine Insufficiency (PEI) Symptoms | End of Drug Period | 0.382 score on a scale |
| Placebo | Patient-reported Change in Pancreatic Exocrine Insufficiency (PEI) Symptoms | Baseline | 0.376 score on a scale |
| Placebo | Patient-reported Change in Pancreatic Exocrine Insufficiency (PEI) Symptoms | End of Drug Period | 0.346 score on a scale |
p-value: 0.52t-test, 2 sided