Imaging Biomarkers of Pancreatic Function and Disease

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест 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.
• Диагностический тест 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.
• Генная терапия 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.
• Диагностический тест Blood Tests
  Research blood draw (for markers of pancreatic endocrine insufficiency)
• Диагностический тест Stool Tests
  Research stool collection (for fecal elastase as a marker of exocrine insufficiency)
• Другое 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.
• Диагностический тест 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.
• Препарат 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

Первичные конечные точки

• Pancreas volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency). [Срок оценки: 5 years]
• Pancreas volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency). [Срок оценки: 5 years]
• Pancreas T1 signal as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency). [Срок оценки: 5 years]
• Pancreas T1 signal as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency). [Срок оценки: 5 years]
• Pancreas secreted fluid volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency). [Срок оценки: 5 years]
• Pancreas secreted fluid volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency). [Срок оценки: 5 years]
• Frequency of genetic mutations in patients progressing to diabetes vs. those not [Срок оценки: 5 years]

Критерии участия

Aim 1-

Patient Group:

Критерии включения

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

Критерии исключения

• 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:

Критерии включения

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

Критерии исключения

• 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:

Критерии включения

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

Критерии исключения

• 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:

Критерии включения

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

Критерии исключения

• 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:

Критерии включения

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

Критерии исключения

• 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:

Критерии включения

• Age 5 to <21 years

Критерии исключения

• 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:

Критерии включения

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

Критерии исключения

• 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:

Критерии включения

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

Критерии исключения

• 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:

Критерии включения

• Age 5 to <21 years
• Clinical diagnosis of chronic pancreatitis

Критерии исключения

• 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-

Критерии включения

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

Критерии исключения

• 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-

Критерии включения

• MRI performed at CCHMC

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

США · 1 центр

• Cincinnati Children's Hospital Medical Center — Cincinnati

Идентификаторы

NCT: NCT05659147 · 2022-0779 · R01DK132346

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗