Pancreatic Enzyme Replacement and Glucose Regulation in Type 1 Diabetes (CREON)

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).

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: CREON

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Active Comparator: CREON; CREON is a pancreatic enzyme replacement	Drug: 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.

What is the study measuring?

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 via c-peptide AUC 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 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.	through study completion (4-5 weeks)

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Daniel Moore, MD, PhD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2022
• Primary Completion (Actual): March 22, 2024
• Study Completion (Actual): March 22, 2024

Study Registration Dates

• First Submitted: February 14, 2022
• First Submitted That Met QC Criteria: February 23, 2022
• First Posted (Actual): March 4, 2022

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 18, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 210734

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plans to share PHI.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No