Imaging Biomarkers of Pancreatic Function and Disease

Summary

This study seeks to understand the performance of MRI to characterize pancreatitis and predict chronic complications (endocrine and exocrine) of pancreatitis. Through multiple aims, the investigators will benchmark MRI against relevant reference standards (e.g. endoscopic pancreatic function tests, laboratory data). The investigators will also characterize repeatability of the imaging findings and will work to develop methods to simplify and automate analysis of the MRI images.

Research interventions depend on the Aim(s) participants enroll in but include: endoscopic pancreatic function testing (added on to clinically indicated upper GI endoscopy), blood tests, stool tests, gene sequencing, and survey completion. All participants will undergo research MRI examinations, a subset of which will include administration of intravenous secretin.

Conditions

• Pancreatitis
• Diabetes Mellitus

Interventions

DIAGNOSTIC_TEST

Research MRI without administration of intravenous secretin

Participants will undergo a research MRI examination. MRI images will be quantitatively analyzed and will be compared to / used to predict diabetes.

DIAGNOSTIC_TEST

Research MRI with administration of intravenous secretin

Participants will undergo a research MRI examination with intravenous administration of secretin. MRI images will be quantitatively analyzed and will be compared to / used to predict exocrine and endocrine pancreatic insufficiency based on the reference standards of ePFTs or fecal elastase and blood hemoglobin A1c (HbA1c) and fasting glucose, respectively.

GENETIC

Genetic Sequencing

Blood will be drawn to enable gene sequencing for gene mutations associated with heritable pancreatitis. We will assess the association between identified gene variants and the presence of diabetes and will construct models based on identified variants to predict progression to diabetes.

DIAGNOSTIC_TEST

Blood Tests

Research blood draw (for markers of pancreatic endocrine insufficiency)

DIAGNOSTIC_TEST

Stool Tests

Research stool collection (for fecal elastase as a marker of exocrine insufficiency)

OTHER

Survey Completion

Participants will be contacted to complete a survey and their charts will be reviewed annually after research MRI to identify any evidence of subsequent development of pancreatic endocrine insufficiency or progression of pancreatitis. Survey and chart review will occur within +/- 14 days of the anniversary date.

DIAGNOSTIC_TEST

Endoscopic pancreatic function tests (ePFTs)

At least two duodenal fluid aspirates will be collected over 15 minutes following secretin administration. Aspirates will be immediately pH tested and will be submitted for analysis of bicarbonate, enzyme (trypsin, amylase, lipase, chymotrypsin) activity, and total protein.

DRUG

Secretin

Participants enrolled in Aim 1, Aim 3, and Aim 4 will receive intravenous secretin at a dose of 0.2 mcg/kg (maximum 16 mcg). Participants in Aim 1 will receive two doses (1 during endoscopy and 1 during MRI). Participants in Aim 3 will receive one dose during MRI. Participants in Aim 4 will receive two doses (1 during each MRI). Secretin for intravenous use is FDA-approved for stimulation of pancreatic secretions, including bicarbonate, to aid in the diagnosis of exocrine pancreas dysfunction. Safety and effectiveness of secretin in pediatrics have not been established. However, secretin is routinely used in children at CCHMC at the same dose at which it will be administered for this study.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• Children's Hospital Medical Center, Cincinnati

  lead OTHER

Principal Investigators

• Andrew Trout, MD · Children's Hospital Medical Center, Cincinnati

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

5 Years

Max Age

21 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-01-18

Primary Completion

2026-12-31

Completion

2027-12-31

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations