Imaging Biomarkers of Pancreatic Function and Disease

NCT05659147 | Enrolling By Invitation Phase 4 FDA Drug FDA Device

• 2 other identifiers: 2022-0779R01DK132346
• Study Type: interventional
• Target: 195
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

MRI

Outcome Measures

Primary Outcomes (7)

• Pancreas volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).

  2 x 2 table analyses of pancreas volume (categorized as normal vs. abnormal) vs. exocrine function (categorized as normal vs. abnormal)

  5 years

• Pancreas volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).

  2 x 2 table analyses of pancreas volume (categorized as normal vs. abnormal) vs. endocrine function (categorized as normal vs. abnormal)

  5 years

• Pancreas T1 signal as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).

  2 x 2 table analyses of pancreas T1 signal (categorized as normal vs. abnormal) vs. exocrine function (categorized as normal vs. abnormal)

  5 years

• Pancreas T1 signal as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).

  2 x 2 table analyses of pancreas T1 signal intensity (categorized as normal vs. abnormal) vs. endocrine function (categorized as normal vs. abnormal)

  5 years

• Pancreas secreted fluid volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).

  2 x 2 table analyses of pancreas secreted fluid volume (categorized as normal vs. abnormal) vs. exocrine function (categorized as normal vs. abnormal)

  5 years

• Pancreas secreted fluid volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).

  2 x 2 table analyses of pancreas secreted fluid volume (categorized as normal vs. abnormal) vs. endocrine function (categorized as normal vs. abnormal)

  5 years

• Frequency of genetic mutations in patients progressing to diabetes vs. those not

  Frequency of genetic mutations in each study group will be compared using 2x2 tables to identify mutations associated with development of diabetes

  5 years

Study Arms (5)

Imaging markers of exocrine and endocrine insufficiency

EXPERIMENTAL

We will prospectively enroll 85 participants; 40 with known or suspected EPI and 45 controls (no known organic gastrointestinal pathology and no history of pancreatic disease) in this aim. Participants will be undergoing clinically-indicated endoscopy and will have endoscopic pancreatic function tests (ePFTs) collected for research during the clinically-indicated endoscopy examination. A research blood draw and a research stool collection will also be collected from all participants. Participants will undergo a research MRI examination with administration of intravenous secretin within 2 weeks of their clinical endoscopy but no sooner than 2 hours before or after endoscopy.

Diagnostic Test: Research MRI with administration of intravenous secretin; Diagnostic Test: Blood Tests; Diagnostic Test: Stool Tests; Other: Survey Completion; Diagnostic Test: Endoscopic pancreatic function tests (ePFTs); Drug: Secretin

Imaging markers of diabetes and prediction of progression to diabetes

EXPERIMENTAL

We will prospectively enroll 30 participants; 10 with a single episode of acute pancreatitis, 10 with acute recurrent pancreatitis, and 10 with pancreatitis-related diabetes in this aim. Participants will undergo a research MRI examination. Participants will also undergo a research blood draw for laboratory analysis and 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: Research MRI without administration of intravenous secretin; Genetic: Genetic Sequencing; Diagnostic Test: Blood Tests; Other: Survey Completion

Imaging stratification of stages of pancreatitis

EXPERIMENTAL

We will prospectively enroll 60 participants; 15 healthy controls, 15 participants with a single episode of acute pancreatitis, 15 participants with acute recurrent pancreatitis, and 15 participants with chronic pancreatitis. A research blood draw and a research stool collection will be collected from all participants. Participants will undergo a research MRI examination with administration of intravenous secretin.

Diagnostic Test: Research MRI with administration of intravenous secretin; Diagnostic Test: Blood Tests; Diagnostic Test: Stool Tests; Other: Survey Completion; Drug: Secretin

Imaging reproducibility

EXPERIMENTAL

We will prospectively enroll up to 20 participants enrolled in Aims 1 or 3 (up to 5 controls and 15 patients with pancreatic disease) to undergo repeat research MRI imaging between 24 hours and 14 days after their first research MRI. Participants will undergo a research MRI examination with administration of intravenous secretin, identical to the research MRI performed under Aims 1 or 3. MRI images will be quantitatively analyzed and agreement between the two MRI examinations (1st and repeat MRI) will be assessed.

Diagnostic Test: Research MRI with administration of intravenous secretin; Drug: Secretin

Automated or semi-automated image analysis

NO INTERVENTION

We will use images prospectively collected under Aims 1-3, as well as existing images that had been obtained for clinical care of children with pancreatitis at CCHMC to develop and optimize image processing pipelines for MRI images. Performance of these pipelines will be benchmarked against manual segmentation performed by multiple observers.

Interventions

Research MRI without administration of intravenous secretin DIAGNOSTIC_TEST

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

Imaging markers of diabetes and prediction of progression to diabetes

Research MRI with administration of intravenous secretin DIAGNOSTIC_TEST

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.

Imaging markers of exocrine and endocrine insufficiency; Imaging reproducibility; Imaging stratification of stages of pancreatitis

Genetic Sequencing GENETIC

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.

Imaging markers of diabetes and prediction of progression to diabetes

Blood Tests DIAGNOSTIC_TEST

Research blood draw (for markers of pancreatic endocrine insufficiency)

Imaging markers of diabetes and prediction of progression to diabetes; Imaging markers of exocrine and endocrine insufficiency; Imaging stratification of stages of pancreatitis

Stool Tests DIAGNOSTIC_TEST

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

Imaging markers of exocrine and endocrine insufficiency; Imaging stratification of stages of pancreatitis

Survey Completion OTHER

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.

Imaging markers of diabetes and prediction of progression to diabetes; Imaging markers of exocrine and endocrine insufficiency; Imaging stratification of stages of pancreatitis

Endoscopic pancreatic function tests (ePFTs) DIAGNOSTIC_TEST

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.

Imaging markers of exocrine and endocrine insufficiency

Secretin DRUG

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.

Imaging markers of exocrine and endocrine insufficiency; Imaging reproducibility; Imaging stratification of stages of pancreatitis

Eligibility Criteria

• Age: 5 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 5 to \<21 years
• Scheduled for clinically-indicated gastrointestinal endoscopy
• Clinical diagnosis or suspicion of exocrine pancreatic insufficiency

You may not qualify if:

• Complete fatty replacement of pancreas on prior imaging
• Current acute pancreatitis or acute pancreatitis less than 30 days prior to research MRI
• Need for sedation for MRI
• Contraindication to MRI (implanted metal hardware)
• Allergy to secretin
• Pregnancy
• Control Group:
• Age 5 to \<21 years
• Scheduled for clinically-indicated gastrointestinal endoscopy
• Sweat chloride \>60 mmol/L
• Clinical diagnosis of gastrointestinal pathology
• Clinical diagnosis or history of pancreatic disease
• Complete fatty replacement of pancreas on prior imaging
• Current acute pancreatitis or acute pancreatitis less than 30 days prior to research MRI
• Need for sedation for MRI

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Pancreatitis; Diabetes Mellitus

Interventions

Hematologic Tests; Occult Blood; Secretin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Officials

• Andrew Trout, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be prospectively recruited to one or more of four prospective imaging aims (Aims 1-4). All participants who enroll in any imaging Aim will have their images used for Aim 5 (image analysis aim) which will also include a retrospective component.

Study Record Dates

• First Submitted: November 22, 2022
• First Posted: December 21, 2022
• Study Start: January 18, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 18, 2026

Record last verified: 2025-09

Locations

US (1)