Pancreatic Enzyme Replacement and Glucose Regulation in Type 1 Diabetes

NCT05266963 | Completed Early Phase 1 Results FDA Drug

• 1 other identifier: 210734
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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).

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (2)

• 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)

Study Arms (2)

CREON

ACTIVE COMPARATOR

CREON is a pancreatic enzyme replacement

Drug: CREON

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

CREON DRUG

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.

CREON

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Pancrelipase

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Lipase; Carboxylic Ester Hydrolases; Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes; Pancreatic Extracts; Tissue Extracts; Complex Mixtures

Limitations and Caveats

The intervention was given for a relatively short time, most patients had significantly reduced pancreas volume, and most had long histories of T1D. The baseline C-peptide levels in the subjects were very low. Assessment in individuals with new onset T1D, in younger subjects, or in individuals with greater residual beta cell function could produce different results.

Results Point of Contact

• Title: Dan Moore, M.D., Ph.D.
• Organization: Vanderbilt University Medical Center

daniel.moore@vumc.org

615-322-7247

Study Officials

• Daniel Moore, MD, PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Model Details: Participants will receive CREON and placebo in a random, blinded order.

Study Record Dates

• First Submitted: February 14, 2022
• First Posted: March 4, 2022
• Study Start: September 2, 2022
• Primary Completion: March 22, 2024
• Study Completion: March 22, 2024
• Last Updated: March 28, 2025
• Results First Posted: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)