Clinical trial NCT05659147: Imaging Biomarkers of Pancreatic Function and Disease
Official title: Imaging Biomarkers of Pancreatic Function and Disease
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE4
Conditions: Pancreatitis
Diabetes Mellitus
Keywords: MRI
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2022-12-21
Enrollment: 195
Sex: ALL
Minimum age (years): 5
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: DIAGNOSTIC

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.

Detailed description: Pancreatitis can be acute \[AP\], acute recurrent \[ARP\] (defined as two discrete attacks with interval resolution), or chronic \[CP\]. Adult studies show that up to 40% of patients develop abnormal glucose metabolism after a single attack of AP, with a 2.5x increased risk of diabetes. CP is defined, in part, by the presence of established endocrine (diabetes) or exocrine pancreatic insufficiency \[EPI\]. Currently, it is not possible to non-invasively diagnose or predict development of pancreatitis-related endocrine or exocrine insufficiency.

The investigator's data has shown that CFTR gene variants play a significant role in progression to diabetes post first attack AP. Existing literature suggests that imaging findings such as decreased pancreas volume are associated with diabetes, but this has not been systematically studied in children.

EPI, defined as insufficient secretion of digestive enzymes and fluid by the pancreas, can have significant effects in childhood including malnutrition, osteoporosis, and growth failure. If diagnosed early, EPI can be treated with pancreatic enzyme replacement, improving nutrition and stabilizing growth. Unfortunately, diagnosing EPI early and accurately is a challenge in children and it is currently not possible to predict progression to CP or development of EPI.

Magnetic resonance imaging (MRI) is a powerful, non-invasive technique, capable of characterizing pancreatic disease. Quantitative non-contrast MRI techniques are attractive as potential markers of pancreatic disease but they have not been validated for diagnosis or prediction of diabetes or EPI in children and they have not been explored for staging of pediatric pancreatitis.

The overall goals of this study are to:

1. Define associations between non-invasive, quantitative MRI measures and established measures of pancreas health and function including diabetes and EPI in children
2. Identify clinical, genetic and imaging-related factors that predict progression to diabetes in children with pancreatitis.

Eligibility criteria: Aim 1-

Patient Group:

Inclusion Criteria:

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

Exclusion Criteria:

* 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:

Inclusion Criteria:

* Age 5 to \<21 years
* Scheduled for clinically-indicated gastrointestinal endoscopy

Exclusion Criteria:

* 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
* Contraindication to MRI (implanted metal hardware)
* Allergy to secretin
* Pregnancy

Aim 2-

Acute Pancreatitis Group:

Inclusion Criteria:

* Age 5 to \<21 years
* Clinically documented episode of acute pancreatitis

Exclusion Criteria:

* More than one episode of acute pancreatitis
* 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)
* Pregnancy

Acute Recurrent Pancreatitis Group:

Inclusion Criteria:

* Age 5 to \<21 years
* Clinical diagnosis of acute recurrent pancreatitis

Exclusion Criteria:

* 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)
* Pregnancy

Pancreatitis-Related Diabetes Group:

Inclusion Criteria:

* Age 5 to \<21 years
* Clinical diagnosis of pancreatitis-related diabetes

Exclusion Criteria:

* 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)
* Pregnancy

Aim 3-

Control Group:

Inclusion Criteria:

• Age 5 to \<21 years

Exclusion Criteria:

* Sweat chloride \>60 mmol/L
* Clinical diagnosis of gastrointestinal pathology
* Clinical diagnosis or history of pancreatic disease, including acute pancreatitis
* Need for sedation for MRI
* Contraindication to MRI (implanted metal hardware)
* Allergy to secretin
* Pregnancy

Acute Pancreatitis Group:

Inclusion Criteria:

* Age 5 to \<21 years
* Clinically documented episode of acute pancreatitis

Exclusion Criteria:

* More than one episode of acute pancreatitis
* 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

Acute Recurrent Pancreatitis Group:

Inclusion Criteria:

* Age 5 to \<21 years
* Clinical diagnosis of acute recurrent pancreatitis with no evidence of CP or EPI

Exclusion Criteria:

* 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

Chronic Pancreatitis Group:

Inclusion Criteria:

* Age 5 to \<21 years
* Clinical diagnosis of chronic pancreatitis

Exclusion Criteria:

* 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

Aim 4-

Inclusion Criteria:

* Age 5 to \<21 years
* Completed research MRI under Aims 1 or 3 of this study

Exclusion Criteria:

* Failed/unable to complete first research MRI under Aims 1 or 3
* Episode of acute pancreatitis since first research MRI
* Current acute pancreatitis
* Any gastrointestinal surgery or pancreas intervention (e.g. ERCP) since first research MRI
* Need for sedation for MRI
* Contraindication to MRI (implanted metal hardware)
* Allergy to secretin
* Pregnancy

Aim 5-

Inclusion Criteria:

• MRI performed at CCHMC

Exclusion Criteria:

* Severe image artifact compromising image quality (judgement of study team)
* Age \>21 years

Primary outcomes:
measure: Pancreas volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).
timeFrame: 5 years
measure: Pancreas volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).
timeFrame: 5 years
measure: Pancreas T1 signal as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).
timeFrame: 5 years
measure: Pancreas T1 signal as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).
timeFrame: 5 years
measure: Pancreas secreted fluid volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).
timeFrame: 5 years
measure: Pancreas secreted fluid volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).
timeFrame: 5 years
measure: Frequency of genetic mutations in patients progressing to diabetes vs. those not
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Andrew Trout, MD
role: PRINCIPAL_INVESTIGATOR
References: