Pancreatic Enzyme Replacement and Glucose Regulation in Type 1 Diabetes

Study Overview
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Brief Summary
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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).

Official Title
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Pancreatic Enzyme Replacement and Glucose Regulation in Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: CREON
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will receive CREON and placebo in a random, blinded order.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CREON<br>CREON is a pancreatic enzyme replacement | Drug: CREON<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in glucose regulation | Mixed meal tolerance testing (MMTT) will be used to assess glucose regulation at baseline, and after treatment with placebo and creon in a random order. | through study completion (4-5 weeks) | 
| Patient-reported change in pancreatic exocrine insufficiency (PEI) symptoms | We will use the PEI questionnaire to quantitate symptoms of PEI and their relative change at baseline and after treatment with placebo and creon in a random order. | through study completion (4-5 weeks) |