Imaging Biomarkers of Pancreatic Function and Disease
试验速览
- 阶段
- 4 期
- 状态
- Enrolling By Invitation
- 入组人数
- 195
- 试验地点
- 1
- 主要终点
- Frequency of genetic mutations in patients progressing to diabetes vs. those not
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patient Group:
- •Inclusion Criteria:
- •Age 5 to <21 years
- •Scheduled for clinically-indicated gastrointestinal endoscopy
- •Clinical diagnosis or suspicion of exocrine pancreatic insufficiency
排除标准
- •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
- •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
- •Control Group:
- •Inclusion Criteria:
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研究组 & 干预措施
Imaging markers of exocrine and endocrine insufficiency
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.
干预措施: Research MRI with administration of intravenous secretin (Diagnostic Test)
Imaging markers of exocrine and endocrine insufficiency
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.
干预措施: Blood Tests (Diagnostic Test)
Imaging markers of exocrine and endocrine insufficiency
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.
干预措施: Stool Tests (Diagnostic Test)
Imaging markers of exocrine and endocrine insufficiency
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.
干预措施: Survey Completion (Other)
Imaging markers of exocrine and endocrine insufficiency
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.
干预措施: Endoscopic pancreatic function tests (ePFTs) (Diagnostic Test)
Imaging markers of exocrine and endocrine insufficiency
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.
干预措施: Secretin (Drug)
Imaging markers of diabetes and prediction of progression to diabetes
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.
干预措施: Research MRI without administration of intravenous secretin (Diagnostic Test)
Imaging markers of diabetes and prediction of progression to diabetes
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.
干预措施: Genetic Sequencing (Genetic)
Imaging markers of diabetes and prediction of progression to diabetes
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.
干预措施: Blood Tests (Diagnostic Test)
Imaging markers of diabetes and prediction of progression to diabetes
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.
干预措施: Survey Completion (Other)
Imaging stratification of stages of pancreatitis
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.
干预措施: Research MRI with administration of intravenous secretin (Diagnostic Test)
Imaging stratification of stages of pancreatitis
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.
干预措施: Blood Tests (Diagnostic Test)
Imaging stratification of stages of pancreatitis
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.
干预措施: Stool Tests (Diagnostic Test)
Imaging stratification of stages of pancreatitis
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.
干预措施: Survey Completion (Other)
Imaging stratification of stages of pancreatitis
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.
干预措施: Secretin (Drug)
Imaging reproducibility
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.
干预措施: Research MRI with administration of intravenous secretin (Diagnostic Test)
Imaging reproducibility
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.
干预措施: Secretin (Drug)
Automated or semi-automated image analysis
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.
结局指标
主要结局
Frequency of genetic mutations in patients progressing to diabetes vs. those not
时间窗: 5 years
Frequency of genetic mutations in each study group will be compared using 2x2 tables to identify mutations associated with development of diabetes
Pancreas volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).
时间窗: 5 years
2 x 2 table analyses of pancreas volume (categorized as normal vs. abnormal) vs. exocrine function (categorized as normal vs. abnormal)
Pancreas T1 signal as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).
时间窗: 5 years
2 x 2 table analyses of pancreas T1 signal (categorized as normal vs. abnormal) vs. exocrine function (categorized as normal vs. abnormal)
Pancreas secreted fluid volume as a predictor of pancreas health and function (including endocrine and exocrine pancreatic insufficiency).
时间窗: 5 years
2 x 2 table analyses of pancreas secreted fluid volume (categorized as normal vs. abnormal) vs. exocrine function (categorized as normal vs. abnormal)
次要结局
未报告次要终点