Clinical trial NCT02869893
Conditions: Healthy Volunteers
Sponsor: Children's Hospital Medical Center, Cincinnati
Start date: 2016-08-10; Completion date: 2017-04-06
Enrollment: 57 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this research study is to learn more about the pancreas. The investigators want to use Magnetic Resonance Cholangiopancreatography (MRCP) to learn more about the size of a normal pancreas. MRCP is a special kind of MRI exam that produces detailed images of the pancreas. The investigators also want to figure out how much fluid the pancreas releases in response to secretin. Secretin is a chemical in the body that causes the pancreas to release fluid that helps with digestion. Secretin is used during the MRCP (MR-PFT) to help identify dysfunction of the pancreas. MR elastography (MRE) will be used to measure how hard the pancreas is. MRE is a special kind of MRI that uses vibrations to image tissue.

Detailed description:
Introduction/Methods: Pancreatic fibrosis is the end stage of chronic pancreatitis (CP), which leads to loss of acinar volume and secretory capacity, and ultimately pancreatic insufficiency (PI). CP and congenital PI affect the pediatric population, and are both increasingly recognized in children. PI has serious negative implications on a child's growth and health but, if diagnosed early, PI can be treated, minimizing the detrimental effects of PI. Currently, direct pancreatic function testing (PFT) via collection of pancreatic fluid is the "gold standard" for diagnosis of PI but it is an invasive testing that may require sedation or general anesthesia. Magnetic resonance cholangiopancreatography (MRCP) with secretin administration (MR-PFT) and MR elastography (MRE) may allow non-invasive, and potentially early diagnosis of CP and PI. Currently, however, normative data with which to compare MR-PFT and MRE results in pediatric patients with suspected CP/PI is not available.

Aims: The investigators propose to determine the normal range for secreted pancreatic fluid volume in response to secretin administration and determine the normal range for pancreatic parenchymal stiffness in a pediatric population that is not affected by pancreatic disease. To date, the investigators have validated their MRCP technique and have successfully performed both MR-PFT and MRE in CP patients; however normative data is essential for validation of our non-invasive technique.

Arms: arm 1: MRCP with Secretin and MR elastography will be performed on all participants.
Interventions: intervention 1: Secretin
Intervention descriptions: intervention 1: None

Protocol documents:
Prot_SAP_000.pdf: 
MRCP: A Reliable, Non Invasive Method for Staging 
Chronic Pancreatitis in Pediatrics 
 
Protocol Document 
May 2, 2018 
NCT02869893 


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STUDY TITLE: Magnetic Resonance Cholangiopancreatography (MRCP) A Reliable, 
Non Invasive Method for Staging Chronic pancreatitis from Minimal Change Disease to 
the Advanced Stages in Pediatrics 
 
 
 
ABSTRACT:  
Introduction/Methods: Pancreatic fibrosis is the end stage of chronic pancreatitis (CP), which 
leads to loss of acinar volume and secretory capacity, and ultimately pancreatic insufficiency 
(PI). CP and congenital PI affect the pediatric population, and are both increasingly recognized 
in children. PI has serious negative implications on a child’s growth and health but, if diagnosed 
early, PI can be treated, minimizing the detrimental effects of PI. Currently, direct pancreatic 
function testing (PFT) via collection of pancreatic fluid is the “gold standard” for diagnosis of PI 
but it is an invasive testing that may require sedation or general anesthesia. Magnetic 
resonance cholangiopancreatography (MRCP) with secretin administration (MR-PFT) and MR 
elastography (MRE) may allow non-invasive, and potentially early diagnosis of CP and PI. 
Currently, however, normative data with which to compare MR-PFT and MRE results in 
pediatric patients with suspected CP/PI is not available. Aims: Herein, we propose to determine 
the normal range for secreted pancreatic fluid volume in response to secretin administration and 
determine the normal range for pancreatic parenchymal stiffness in a pediatric population that is 
not affected by pancreatic disease.  Additionally, we will assess visibility of the pancreatic duct 
pre and post administration of secretin.   To date, we have validated our MRCP technique and 
have successfully performed both MR-PFT and MRE in CP patients; however normative data is 
essential for validation of our non-invasive technique. Conclusion: Normative pediatric data 
derived from this study will provide a baseline against which future studies of pediatric patients 
with suspected CP and PI can be assessed. Additionally, the techniques described herein might 
also be leveraged in the future in the adult population. 
 
 
PURPOSE OF STUDY:  
Collect normative data for pancreatic state (the size, volume, anatomy, biliary and 
vascular structures) as well as the volume of secreted fluid in response to secretin 
administration in a representative sample of healthy pediatric controls.  
 
Determine secreted volumes: Hypothesis 1. Total secreted fluid volume as measured by MR-
PFT will correlate with subject size and age. Exp 1. MR-PFT will be performed in 50 healthy 
pediatric subjects including 25 subjects ages 6-11.9 years and 25 subjects 12-15.9 years. 
Secreted volumes will be correlated with subject age and height, weight, body mass index and 
body surface area.  
 
Collect normative data for pancreatic stiffness as measured by MR elastography. 
Hypothesis 2. Pancreatic parenchymal stiffness in the pediatric population will fall in a normative 
range similar to adult norms and will not depend on subject age or size. Exp 2. Pancreatic 
parenchymal stiffness will be measured in the same healthy cohort of 50 healthy pediatric 
subjects including 25 subjects ages 6-11.9 years and 25 subjects 12-15.9 years.  
 
Assess the relationship between pancreatic exocrine function, pancreatic stiffness and 
pancreatic parenchymal volume. Hypothesis 3. Pancreatic exocrine function as measured by 
MR-PFT and pancreatic stiffness as measured by MRE will be dependent on pancreatic 
parenchymal volume. Exp 3. Secreted fluid volumes as measured by MR-PFT and pancreatic 


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stiffness as measured by MRE will be correlated with volumetric measurements of pancreatic 
parenchymal volume. 
 
Assess the effect of secretin on the visibility of the pancreatic duct.  Hypothesis 4.  A 
subjective, blinded assessment of pancreatic duct visibility pre-and post-secretin will show an 
increase in visibility on post-secretin images. 
  
We will also store this data to identify normative values in controls for pancreatic and any other 
gastrointestinal parameters in MRCP.  
 
Significance and Innovation:  
Our study will add significant information to the existing literature regarding diagnosis and 
staging of CP, and will set the foundation for using MR as a non-invasive biomarker for CP/PI in 
pediatrics. Our study is novel because it will investigate the use of MRI for assessing pancreatic 
anatomy, function, and stiffness in the pediatric population. It will also shed light on 
gastrointestinal anatomy and function in pediatric healthy controls which has not yet been 
described in the literature. Moreover, the results of our study will fill a knowledge gap regarding 
normal secretory function of the pancreas in children. 
 
 
BACKGROUND:  
Chronic pancreatitis (CP) is a morbid condition with poor quality of life, significant pain, and 
negative impact on growth, health and overall wellbeing 1-4. Late stages of the disease, manifest 
as parenchymal fibrosis and loss of function (pancreatic insufficiency (PI)), are easier to 
diagnose than mild and early stages (minimal change disease). If CP is recognized early, 
therapies to treat mild disease and halt the progression to PI could be applied 5-8. As such, 
studies geared toward early detection are needed to identify minimal change disease and allow 
early therapeutic intervention. Once PI is suspected, direct pancreatic function testing (PFT) is 
the gold standard for assessment of pancreatic exocrine function. PFTs, as currently performed, 
are invasive and require sedation/anesthesia 9, 10. Potential non-invasive means of assessing 
pancreatic structure and function include magnetic resonance cholangiopancreatography 
(MRCP) and MR elastography (MRE)11, 12. In adult patients, MRCP with secretin stimulation has 
been demonstrated to allow non-invasive assessment of pancreatic exocrine function 13. MRCP 
for assessment of pancreatic exocrine function (MR-PFT), however, has not been validated in 
children and normative data are not available, limiting the utility of this test in the pediatric 
population. MR Elastography uses transmitted vibrations to assess tissue stiffness and early 
studies have shown efficacy in measuring pancreatic stiffness in adult patients 14, 15. By 
measuring pancreatic stiffness, MRE might be utilized as a non-invasive assessment measure 
of developing pancreatic fibrosis which may serve as a biomarker of minimal change CP 14.  
 
In preparation for this study, we developed a protocol to measure pancreatic fluid volume 
secreted in response to secretin administration, confirmed feasibility of pancreatic stiffness 
measurements by MRE and analyzed our experience with MR in pediatric patients with 
pancreatic disease, primarily CP. We have a cohort of CP patients that have undergone MRCP 
with the proposed study protocol and we will continue to collect data on CP patients that 
undergo MR studies. The overall aim of this pilot-study is to collect MR-PFT and MRE data in a 
small group of normal pediatric subjects (with no history of pancreatic disease, CP/PI, or 
intestinal disease) to serve as a preliminary data set for a subsequent comparative study of MR-
PFT and MRE in children with CP. The ultimate aim is to provide results that would position 
non-invasive MR studies as an accurate, sensitive, and specific alternative to standard 
modalities of CP diagnosis and therapy monitoring (endoscopic PFT (ePFT), endoscopic 


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retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS), and biopsy). Our 
overall hypothesis is that normative ranges can be established for total secreted 
pancreatic fluid volume as measured by MR-PFT and for pancreatic stiffness as 
measured by MRE and that secreted volumes but not pancreatic stiffness will depend on 
subject age and size. 
 
 
STUDY DESIGN:  
This will be a single center prospective study of children with no history of pancreatic disease to 
quantify normal pancreatic volumes and secreted fluid volume (SV) in response to secretin 
administration as measured by MR-PFT. We will also assess the pancreatic stiffness by MR 
elastography as well as pancreatic duct visibility (pre-and post-secretin) in the same cohort.  
 
MR elastography: 
MRE equipment consists of an active and a passive driver system. The passive driver is 
connected to the active driver in the equipment room by a wave-guide with a hollow plastic tube. 
The active driver generates low amplitude 60 Hz vibrations which are passed via pneumatic 
pressure to the passive driver which is placed on the patient’s abdomen.  The initiation and 
cessation of the vibrations are controlled by the MR pulse sequence programmed and 
embedded as part of the scanner software. The MRE pulse sequence does not bypass any 
scanner safety standards as specified by the manufacturer.  The MRE sequence will produce 
magnitude and phase images at multiple levels in the pancreas. After the MRE magnitude and 
phase images are obtained, the data is converted into quantitative images displaying the 
stiffness of the pancreatic parenchyma. Stiffness and quantitative mean stiffness values are 
generated from the phase images. The MRE sequence being used as part of this study is an 
investigational sequence with which we have experience in both the clinical and research 
environment. The investigational sequence will be performed in such a way that the Food and 
Drug Administration (FDA) general MR safety guidelines cannot be overridden and/or 
exceeded. 
 
Secretin: 
Synthetic human secretin is a peptide hormone with an amino acid sequence identical to 
naturally occurring secretin. The main action is to increase the secretion of pancreatic juice, 
including bicarbonate by stimulating the exocrine pancreas thereby assisting in the diagnosis of 
exocrine pancreatic dysfunction.  Secretin is FDA approved for pancreatic stimulation use in 
adults. We regularly use secretin in clinical practice at CCHMC. A limited MRCP with secretin 
stimulation with a dose of 0.2 mcg/kg (maximum of 16 mcg) will be performed and post-
processed as detailed below. 
 
MR imaging: 
All studies will be performed on a 1.5T GE HDx MRI scanner (General Electric; Milwaukee, WI) 
using the 8-channel Torso coil. The following sequences will be obtained through the upper 
abdomen:  
 
Pre-Secretin:  
Axial 3D T1 GRE (LAVA) 
Axial fat saturated T2 fast spin echo (FSE) 
Axial 3D GRE magnetic resonance elastography (MRE) 
Axial T2 map 
Coronal 3D fast relaxation fast spin echo (FrFSE) 
Coronal fat saturated T2 SSFSE 


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Post-Secretin:  
Coronal fat saturated T2 SSFSE at 1, 5, 10 and 15 minutes after Secretin injection 
Coronal 3D FrFSE 
 
MR post-processing: 
MR-PFT: 
Total secreted fluid volume in response to secretin will be determined from the pre- and post-
secretin coronal T2 SSFSE using commercially available software (ImageJ, MatLab) by 
selecting a signal intensity threshold which isolates intraluminal fluid in the duodenum and 
proximal jejunum. A region of interest will then be drawn on each image inclusive of thresholded 
pixels, to determine the area (mm2) of fluid signal. The area of fluid signal on each image will 
then be multiplied by the image slice thickness and all slice values will be summed to determine 
a fluid volume over the entire imaged volume. 
 
MRE: 
MR elastography images will be post-processed using software leased from Resoundant 
(Rochester, MN) with pancreatic parenchymal stiffness expressed as a mean stiffness (kPa) for 
the pancreatic neck, body, and tail. 
 
Parenchymal volume: 
Pancreatic parenchymal volume will be measured by manual segmentation of the pancreas 
using commercially available software (MIM, MIM Software Inc.; Cleveland, OH). 
 
 
DURATION: 
This initial pilot study is anticipated to take approximately 12 months but we will continue up to 
24 months if we are not able to meet the recruitment target the first year.  
 
 
RECRUITMENT & CONSENT OF PARTICIPANTS:  
Subject Recruitment: 
Recruited subjects will have no history of pancreatic disease and will be identified through 
review of patients presenting for non-abdominal imaging examinations. Patients presenting for 
musculoskeletal MRI examinations will likely be the major source for recruited patients. In the 
last 2 years, 1297 musculoskeletal MR examinations have been done in pediatric patients, ages 
6 -15 years, at our institution, providing a ready source for recruitment. Subjects may 
additionally be recruited through public recruitment using existing clinical trial recruitment 
services at CCHMC, including advertising within our institution to raise awareness of the study. 
CCHMC employees may be invited to enroll their children in the study; they would be invited by 
the research coordinator. Subject charts will be reviewed for evidence of pancreatitis or other 
pancreatic disease prior to/during enrollment. Following initial screening, subjects will be 
contacted by the study coordinator or an investigator and enrolled after informed consent is 
obtained. During enrollment, absence of exclusion criteria will be confirmed with a questionnaire 
completed prior to imaging. 
 
50 evaluable subjects will be recruited evenly divided as follows: 
25 subjects age 6-11.9 years 
25 subjects age 12-15.9 years 
 
Inclusion Criteria: 


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1. Subjects between the ages of 6 and 15.9 years. 
2. Subjects without a documented history of (or suggestive of) pancreatic disease. 
 
Exclusion Criteria: 
1. History of pancreatic disease, liver disease, intra-abdominal neoplasm, abdominal 
inflammatory process such as inflammatory bowel disease (IBD), or systemic illness that 
may affect pancreatic state (e.g. cystic fibrosis). 
2. Subjects with surgical hardware/implanted devices making them ineligible for MRI (e.g. 
pacemaker or other implanted medical device not approved for MRI). 
3. Subjects who require any form of sedation or general anesthesia for MRI. 
4. Subjects unable to breath-hold for the required 15-20 second imaging sequence. 
5. Subjects who are pregnant or less than 12 months post-partum. 
 
Process of obtaining Consent: 
In accordance with the International Conference on Harmonization – Good Clinical Practices 
(ICH-GCP) and local legislation, all participants/families will be fully informed about the study, 
and the parents will give written informed consent prior to enrollment in the study and prior to 
any study specific procedures being performed.  Participants ≥11 years of age will be asked to 
sign an assent form prior to participating in the study.  
 
All participants will be asked to complete a metal screening form prior to participation in the 
study, regardless of whether or not they have done so in the past.  This will ensure the MR 
screening information is up-to-date for anyone who participates in this protocol. 
 
Females who are able to get pregnant will be screened with a urine pregnancy test prior to 
imaging. Results will be shared with subject and parent, if applicable. 
 
Subjects will be reminded that participation in research is completely voluntary. Coercion is 
eliminated by having the subjects sign an assent document and the parent/guardian signs the 
consent document. Time will be given for families to read the consent documents and for any 
questions to be answered.  
 
 
STUDY PROCEDURES:  
We will contact each family prior to the MRI visit to provide information about the study. Written 
consent will be obtained on the day of the exam.  At that time, absence of exclusion criteria will 
be confirmed with a questionnaire and pregnancy testing for all females of child bearing 
potential will be completed prior to imaging.  
 
MR-PFT (Exp 1) and MRE (Exp 2) exams will each be performed once per subject on a 1.5T 
GE HDx MRI scanner (General Electric; Milwaukee, WI). Subjects will be required to fast (NPO) 
for four hours prior to MR imaging. Subjects will be weighed and measured immediately prior to 
imaging. The IV will be placed by the MRI technologist at the beginning of the imaging 
examination. The patient will then be placed into the scanner and the MRE passive driver will be 
placed on their abdomen. The patient will be provided with standard hearing protection and 
entertainment options (video goggles). All pre-secretin imaging will then be performed. A study 
team physician or a Radiology Department nurse will then inject the secretin through the IV and 
all post-secretin imaging will be performed. Once imaging is completed, the patient will be 
removed from the scanner and the IV will be removed. 
 


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Anticipated duration of MR imaging is approximately 35 minutes scan time (total 50 min in room 
time). Scan time pre-secretin (5 sequences, including MRE) is approximately 20 minutes. Scan 
time post-secretin (sequences for MR-PFT) is approximately 15 minutes. The additional time is 
required for positioning, localization, sequence planning, and secretin injection. The MRI 
examinations can be terminated at any time upon request of the participant. All MR imaging will 
be done as scheduled appointments. 
 
All images will be maintained in the research PACS environment. Data that will be saved will 
include participant number, age at time of examination, and MR data. Identifying data will be 
saved in a password-protected database. 
 
Facilities: 
Visits will be conducted within the main clinical CCHMC Radiology Department.  The MR 
scanner being used is owned and operated by the CCHMC Department of Radiology. 
 
Radiologist Review of Images: 
The imaging protocol used in this study includes only the minimum scanning needed to achieve 
the research objective outlined by the study investigator.  No report will be generated or 
supplied to the research participants.  However, all scans performed for this project will be 
reviewed for gross abnormalities by a board-certified or board-eligible radiologist. Although no 
diagnosis will be made, in the event that abnormal findings are identified, the PI will be informed 
and will assume responsibility for notifying the participant.  In this case written documentation 
that an abnormal finding has been identified will be provided to the participant. 
 
 
DATA ANALYSIS/METHODS: 
Statistical analysis: 
Statistical analyses will be tailored to our study purposes as follows: 
Collect normative data for volume of secreted fluid in response to secretin administration 
in a representative sample of healthy pediatric controls. 
Means, standard deviations and 95% confidence intervals will be used to summarize study 
population secreted volumes. Linear regression will be used to assess for significant correlation 
between subject age and secreted volume. Similar regression models will be used to test other 
body-size covariates such as BSA, BMI, etc. If feasible, a quantile regression will be performed 
of secreted volume or BSA normalized secreted value to attempt to quantify normal range as a 
function of age, BMI, etc. 
 
Collect normative data for pancreatic stiffness as measured by MR elastography. 
Means, standard deviations and 95% confidence intervals will be used to summarize study 
population pancreatic parenchymal stiffness. Linear regression will be used to assess for 
significant correlation between subject age and parenchymal stiffness. Similar regression 
models will be used to test other body-size covariates such as BSA, BMI, etc. 
 
Assess the relationship between pancreatic exocrine function, pancreatic stiffness and 
pancreatic parenchymal volume. 
Linear regression will be used to define correlation between pancreatic parenchymal volume 
and secreted fluid volume in response to secretin administration. 
 
For the stored anatomy and other gastrointestinal functional data from the controls, we will 
conduct statistical analyses according to the purpose of the question that is asked from this 
data, for instance for pancreatic volume measurements, we will conduct a comparison analysis 


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by t test, ANOVA, Wilcoxon test and other measures to fit the purpose of the other future 
studies. 
 
Assess the effect of secretin on the visibility of the pancreatic duct. 
Frequencies and rankings will be compared with Fischer exact test and Wilcoxon rank sum tests 
to compare visualization of the pancreatic duct pre- and post-secretin. 
 
 
 
Power calculation: 
To establish relationship between secreted fluid volume and subject body size or age, we base 
a power calculation on analysis of MR-PFT data in 19 CP patients and the assumption that 
secreted volume is correlated with age in this sample of patients. In a linear regression analysis 
of these patients, the observed residual standard error is approximately 39, with an R2 ~ 0.40.  
The observed regression coefficient is 5.274, and standard deviation of predictor age is ~5.816.  
If this holds in a general population, we require at least 15 normal subjects to have a significant 
regression coefficient at 0.05 level, and 80% power. 
 
Additionally, from the previously reported study of normal adult patients by Mensel et al. [25], 
the coefficient of variation (CV) of secreted volume (TEV in the paper) at various time points 
from secretin injection ranged from 0.30 to 0.51.  Given that we plan to enroll subjects in two 
age groups (6-11.9 and 12-15.9 years old), 25 subjects in each age group will provide 80% 
chance that the 95% confidence interval of mean secreted volume will be within 12% to 20% of 
the mean value, depending on the actual CV observed. 
 
Therefore, we plan to enroll a total of 50 evaluable subjects in the study to meet both needs 
above. 
 
 
POTENTIAL RISKS & BENEFITS:  
Potential Risks: 
The risk category for all subjects who choose to participate in the study will fall into the minimal 
risk category.   
 
MR: There are no known risks from having an MRI.  However, some people are claustrophobic 
and may become anxious, fearful, or nervous in the scanner.  Should participants become 
uncomfortable at any time, the scan will be stopped immediately.  Should any risks related to 
having an MR examination be identified during the course of this study, participants will be 
informed of those risks. 
 
Secretin: The administration of secretin will involve placement of an intravenous catheter (IV), 
which may cause some pain, bleeding, or bruising at the site and in rare instances can result in 
infection. Secretin is associated with some minimal and temporary side effects, such as 
abdominal pain, nausea, or flushing. These effects are minor (if they happen at all) and can be 
easily monitored in patients undergoing MRCP. 
 
Data Safety Monitoring Plan:   
This study is a non-intervention study. Therefore, no formal data safety monitoring board will be 
appointed.  Adverse events related to the study procedures will be monitored by the study 
coordinator and reported to the PI and the Division Director.  The PI will then report any adverse 


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events in writing to the CCHMC IRB within the time frame specified in the IRB guidelines. These 
procedures should be highly effective in minimizing risk to study participants. 
 
Potential Benefits: 
There will be no direct benefits to participants in this study other than potential knowledge of the 
results from the scans that may be shared with them by the clinical staff. This research, 
however, may have generalized benefits in terms of providing a preliminary data set for a 
subsequent comparative study of MR-PFT and MRE in children with CP. 
  
 
PRIVACY & CONFIDENTIALITY: 
Each subject will be assigned a study ID number. A password-protected table will be maintained 
that links the study ID number to the medical record number. This table will be maintained on a 
secure server and/or in a locked file cabinet, as appropriate. The password-protected database 
containing the MRE and MRCP data will be maintained on a secure server with access limited 
to study personnel. Identifying data will be saved in a password-protected database. We plan to 
keep the de-identified data for future studies.  Any data that are extracted from the database 
and used for research will be subject to standard anonymization and data protection practices. 
 
 
COST OF PARTICIPATION:  
There is no cost to participate in this study. 
 
 
PAYMENT FOR PARTICIPATION: 
We will provide each participant/family with a $100 gift card (Clincard) for the reimbursement of 
time and trouble to participate in the study. Compensation will be given at the end of the study 
visit upon completion of the MRI exam. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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REFERENCES: 
1. 
Amann ST, Yadav D, Barmada MM, et al. Physical and mental quality of life in chronic 
pancreatitis: a case-control study from the North American Pancreatitis Study 2 cohort. 
Pancreas 2013;42:293-300. 
2. 
Schwarzenberg SJ, Bellin M, Husain SZ, et al. Pediatric chronic pancreatitis is 
associated with genetic risk factors and substantial disease burden. J Pediatr 
2015;166:890-6 e1. 
3. 
Somaraju UR, Solis-Moya A. Pancreatic enzyme replacement therapy for people with 
cystic fibrosis. Cochrane Database Syst Rev 2014;10:CD008227. 
4. 
Arya VB, Senniappan S, Demirbilek H, et al. Pancreatic endocrine and exocrine function 
in children following near-total pancreatectomy for diffuse congenital hyperinsulinism. 
PLoS One 2014;9:e98054. 
5. 
Conwell DL, Zuccaro G, Jr., Vargo JJ, et al. An endoscopic pancreatic function test with 
cholecystokinin-octapeptide for the diagnosis of chronic pancreatitis. Clin Gastroenterol 
Hepatol 2003;1:189-94. 
6. 
Abu Dayyeh BK, Conwell D, Buttar NS, et al. Pancreatic juice prostaglandin e2 
concentrations are elevated in chronic pancreatitis and improve detection of early 
disease. Clin Transl Gastroenterol 2015;6:e72. 
7. 
Pelley JR, Gordon SR, Gardner TB. Abnormal duodenal [HCO3-] following secretin 
stimulation develops sooner than endocrine insufficiency in minimal change chronic 
pancreatitis. Pancreas 2012;41:481-4. 
8. 
Sendler M, Beyer G, Mahajan UM, et al. Complement Component 5 Mediates 
Development of Fibrosis, via Activation of Stellate Cells, in 2 Mouse Models of Chronic 
Pancreatitis. Gastroenterology 2015;149:765-76 e10. 
9. 
Conwell DL, Zuccaro G, Purich E, et al. The effect of moderate sedation on exocrine 
pancreas function in normal healthy subjects: a prospective, randomized, cross-over trial 
using the synthetic porcine secretin stimulated Endoscopic Pancreatic Function Test 
(ePFT). Am J Gastroenterol 2005;100:1161-6. 
10. 
Conwell DL, Zuccaro G, Purich E, et al. Comparison of endoscopic ultrasound chronic 
pancreatitis criteria to the endoscopic secretin-stimulated pancreatic function test. Dig 
Dis Sci 2007;52:1206-10. 
11. 
Zuccaro P, Stevens T, Repas K, et al. Magnetic resonance cholangiopancreatography 
reports in the evaluation of chronic pancreatitis: a need for quality improvement. 
Pancreatology 2009;9:764-9. 
12. 
Sainani NI, Kadiyala V, Mortele K, et al. Evaluation of Qualitative Magnetic Resonance 
Imaging Features for Diagnosis of Chronic Pancreatitis. Pancreas 2015;44:1280-9. 
13. 
Balci NC, Smith A, Momtahen AJ, et al. MRI and S-MRCP findings in patients with 
suspected chronic pancreatitis: correlation with endoscopic pancreatic function testing 
(ePFT). J Magn Reson Imaging 2010;31:601-6. 


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14. 
Shi Y, Glaser KJ, Venkatesh SK, et al. Feasibility of using 3D MR elastography to 
determine pancreatic stiffness in healthy volunteers. J Magn Reson Imaging 
2015;41:369-75. 
15. 
Itoh Y, Takehara Y, Kawase T, et al. Feasibility of magnetic resonance elastography for 
the pancreas at 3T. J Magn Reson Imaging 2015. 

ICF_001.pdf: 
MRCP: A Reliable, Non Invasive Method for Staging 
Chronic Pancreatitis in Pediatrics 
 
Parental Permission Document 
NCT02869893 
June 30, 2016 
 


IRB #: 2016-2847 
 
 
 
Approved:  
6/7/2018 
Do Not Use After: 
6/6/2019 
 
 
Parental Permission Version – 1.0 
Page 1 of 6
 
STUDY TITLE:  Magnetic Resonance Cholangiopancreatography (MRCP) A Reliable, Non 
Invasive Method for Staging Chronic pancreatitis from Minimal Change Disease to the 
Advanced Stages in Pediatrics 
 
STUDY NUMBER: 2016-2847                
 
FUNDING ORGANIZATION: National Pancreas Foundation 
 
Principal Investigators:  Maisam Abu-El-Haija, MD 
 Andrew Trout, MD  
 
Telephone Number:  513-803-2123 
 
INTRODUCTION 
 
We are asking for your permission for your child to be in a research study so that we can learn new 
information that may help others. If you decide not to give your permission for your child to be in this 
study, we will still take good care of him/her.  If you decide to allow your child to be in this study, you 
may change your mind at any time during the study and your child can stop being in the study.  Take 
all the time you need to make your choice.  Ask us any questions you have. It is also okay to ask 
more questions after you decide to allow your child to be in the study.  You can ask questions at any 
time.   
 
WHY ARE WE DOING THIS RESEARCH? 
 
We are asking your child and other children without pancreatic diseases to be in this research study 
because we need to better understand what the pancreas looks like in healthy children so that we can 
take better care of children with pancreas diseases. 
 
In this research study we want to learn more about the pancreas. We want to use Magnetic 
Resonance Cholangiopancreatography (MRCP) to learn more about the size of a normal pancreas. 
MRCP is a special kind of Magnetic Resonance Imaging (MRI) exam that produces detailed pictures 
of the pancreas.  We also want to figure out how much fluid the pancreas releases in response to 
secretin. Secretin is a chemical in the body that helps with digestion. We use secretin during the 
MRCP (MR-PFT) to help us find dysfunction of the pancreas. We will also measure how hard the 
pancreas is by using MR elastography (MRE).  MRE is a special kind of MRI that uses vibrations to 
image tissue.   
 
We have successfully performed both MR-PFT and MRE in patients with chronic pancreatitis. 
 
 
WHO IS IN CHARGE OF THE RESEARCH?  
 
Maisam Abu-El-Haija, MD is the researcher at Cincinnati Children’s Hospital Medical Center 
(CCHMC) that is in charge of this study.   


IRB #: 2016-2847 
 
 
 
Approved:  
6/7/2018 
Do Not Use After: 
6/6/2019 
 
 
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CCHMC is being paid by The National Pancreas Foundation (a non-profit foundation) to do this study 
with about 50 children. 
 
WHO SHOULD NOT BE IN THE STUDY 
 
Your child cannot be in this study if he/she has any of the following: 
 
1. A history of pancreatic disease, liver disease, abdominal tumor, inflammatory bowel disease (IBD), 
or cystic fibrosis. 
2. Surgically implanted devices making them ineligible for MRI (e.g. pacemaker). 
3. Pregnant or less than 12 months post-partum. 
 
WHAT WILL HAPPEN IN THE STUDY? 
 
You will be able to ask questions to make sure that you understand what will happen to your child. 
 
If your child qualifies and you decide you want your child to be in the study, your child will come to 
CCHMC for one visit. If your child is a girl who has started having periods, we will do a urine 
pregnancy test. Pregnant people cannot be in this research.  We will share the results of the 
pregnancy test with you and your child. 
 
These are the things that will happen to your child while in the study: 
 
MR-PFT and MRE exams will be performed on an MRI scanner. Your child will not be able to eat or 
drink for four hours before the visit.   The MRI technologist will place the IV in your child’s arm at the 
beginning of the exam.  Your child will then be placed into the scanner.  Your child may request video 
goggles for entertainment during the exam. All pre-secretin imaging will be performed first. Next, a 
study team doctor or nurse will inject the secretin through the IV and all post-secretin imaging will be 
performed.  After that, your child will be removed from the scanner and the IV will be removed. 
 
The MR imaging will take about 35 minutes.  Your child will be in the room for about 50 minutes total.  
 
After all imaging is obtained, imaging data will be de-identified for analysis for this study and will be 
kept in de-identified form for potential future study. De-identified means we will remove all personally 
identifying information such as name or medical record number. 
 
WHAT ARE THE GOOD THINGS THAT CAN HAPPEN FROM THIS RESEARCH? 
 
Being in this study may not help your child right now.  When we finish the study, we hope that we will 
know more about using MRI to learn about the pancreas.  This may help children with chronic 
pancreatitis later on. 
 
WHAT ARE THE BAD THINGS THAT CAN HAPPEN FROM THIS RESEARCH? 
 
There are no known risks from having an MRI or from studying the use of the pictures from the MRI. 


IRB #: 2016-2847 
 
 
 
Approved:  
6/7/2018 
Do Not Use After: 
6/6/2019 
 
 
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However, some people are claustrophobic and may become anxious, fearful, or nervous in the MR 
scanner.  If your child becomes uncomfortable at any time the scan will be stopped 
immediately.   
 
We will use an IV, which may cause some pain, bleeding, or bruising at the site. There is a small 
chance for infection. 
 
Secretin may cause abdominal pain, nausea, or flushing. These effects are minor and can be easily 
monitored. 
 
There may be other risks that we do not know about yet.  
 
WHAT OTHER CHOICES ARE THERE? 
 
Instead of being in this study, you can choose not to have your child be in it.   
 
HOW WILL INFORMATION ABOUT YOUR CHILD BE KEPT PRIVATE? 
  
Making sure that information about your child remains private is important to us. To protect your 
child’s privacy in this research study, data that we collect will be stored in locked rooms and password 
protected files.  As soon as we have finished collecting data on all of the participants, we will separate 
identifying information about your child from the data we are collecting. Identifying data will be saved 
in a password-protected database.  Only the primary investigators and select study personnel will 
have access to information that might be used to identify you. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This website will not include information that can identify your child. At most, the website will 
include a summary of the study results. You can search this website at any time. 
 
WHAT IF WE LEARN NEW INFORMATION DURING THE RESEARCH?  
 
The study doctor will tell you if they find out about new information from this or other studies that may 
affect your child’s health, safety or your willingness for your child to be in this study. The results of this 
study will not be made available to you. A member of the study team will notify you if we identify 
clinically significant abnormalities.  
 
WILL IT COST YOU ANYTHING EXTRA FOR YOUR CHILD TO BE IN THE RESEARCH STUDY?  
 
You or your insurance company will not be charged for the research MRI. Your insurance company 
will be charged for your continuing routine medical care including tests and treatments required for 
your clinical care. 
 
 
WILL YOU/YOUR CHILD BE PAID TO BE IN THIS RESEARCH STUDY?  
 
You (your child) will be reimbursed for your time, effort and travel while you are in this research study.   


IRB #: 2016-2847 
 
 
 
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6/7/2018 
Do Not Use After: 
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You will be paid $100 at the end of the study visit upon completion of the MRI exam in the form of a 
reloadable debit card (Clincard).  We will give you a handout that will explain how to use the card.  
Because you are being paid for your participation, CCHMC is required by the Internal Revenue 
Service (IRS) to collect and use your (or your child’s) social security number (SSN) or taxpayer 
identification number (TIN) to track the amount of money that we pay.  You will need to complete a 
Federal W-9 form for this income tax reporting.  This form requires your child’s Social Security 
number.  This form will be given to the CCHMC business office.  It will not be kept as part of your 
child’s study chart.  If you move, you will need to complete another W-9 with an updated address. 
 
 
WHAT HAPPENS IF YOUR CHILD IS INJURED FROM BEING IN THIS STUDY?  
 
If you believe that your child has been injured as a result of this research you should contact Maisam 
Abu-El-Haija, MD (513-803-2123) as soon as possible to discuss the concerns.   
 
CCHMC follows a policy of making all decisions about compensation for the medical treatment of 
physical injuries that happened during or were caused by research on an individual basis. 
 
 
WHO DO YOU CALL IF YOU HAVE QUESTIONS OR PROBLEMS?  
 
For questions, concerns, or complaints about this research study you can contact the study doctor 
listed on page 1 of this document.  
 
If you would like to talk to someone that is not part of the research staff or if you have general 
questions about your research study rights or questions, concerns, or complaints about the research, 
you can call the CCHMC Institutional Review Board at 513-636-8039.  
 
WHAT ELSE SHOULD YOU KNOW ABOUT THE RESEARCH? 
 
The research MRI exams (MR-PFT and MRE) that are being done in this study are the same as MRI 
exams we do routinely at CCHMC.  
 
AUTHORIZATION FOR USE/DISCLOSURE OF HEALTH INFORMATION FOR RESEARCH 
 
To be in this research study you must also give your permission (or authorization) to use and disclose 
(or share) your child’s “protected health information” (called PHI for short).  
 
What protected health information will be used and shared during this study? 
CCHMC will need to use and share your child’s PHI as part of this study.  This PHI will come from: 
 Your child’s CCHMC medical records 
 Your child’s research records 
 
The types of information that will be used and shared from these records include: 
 Laboratory test results, diagnosis, and medications 
 Reports and notes from clinical and research observations 


IRB #: 2016-2847 
 
 
 
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Do Not Use After: 
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 Imaging (like CT scans, MRI scans, x-rays, etc.) studies and reports 
 If applicable, information concerning HIV testing or the treatment of AIDS or AIDS-related 
conditions, drug or alcohol abuse, drug-related conditions, alcoholism, and/or 
psychiatric/psychological conditions (but not psychotherapy notes). 
 
Who will share, receive and/or use your child’s protected health information in this study? 
 Staff at all the research study sites (including CCHMC) 
 Personnel who provide services to your child as part of this study 
 Other individuals and organizations that need to use your child’s PHI in connection with the 
research, including people at the sponsor and organizations that the sponsor may use to oversee 
or conduct the study. 
 The members of the CCHMC Institutional Review Board and staff of the Office of Research 
Compliance and Regulatory Affairs. 
 
How will you know that your child’s PHI is not misused? 
People that receive your child’s PHI as part of the research are generally limited in how they can use 
your child’s PHI.  In addition, most people who receive your child’s PHI are also required by federal 
privacy laws to protect your child’s PHI.  However, some people that may receive your child’s PHI 
may not be required to protect it and may share the information with others without your permission, if 
permitted by the laws that apply to them.   
 
Can you change your mind? 
You may choose to withdraw your permission at any time.  A withdrawal of your permission to use 
and share your child’s PHI would also include a withdrawal from participation in the research study.  If 
you wish to withdraw your permission to use and share your child’s PHI you need to notify the study 
doctor, listed on the first page of this document, in writing.  Your request will be effective immediately 
and no new PHI about your child will be used or shared.  The only exceptions are (1) any use or 
sharing of PHI that has already occurred or was in process prior to you withdrawing your permission 
and (2) any use or sharing that is needed to maintain the integrity of the research. 
 
Will this permission expire? 
Your permission will expire at the end of the study.  If the study involves the creation or maintenance 
of a research database repository, this authorization will not expire.  
 
Will your child’s other medical care be impacted? 
By signing this document you agree for child to participate in this research study and give permission 
to CCHMC to use and share your child’s PHI for the purpose of this research study.  If you refuse to 
sign this document your child will not be able to participate in the study.  However, your child’s rights 
concerning treatment not related to this study, payment for services, enrollment in a health plan or 
eligibility of benefits will not be affected. 
 
 
 
 
 
 


IRB #: 2016-2847 
 
 
 
Approved:  
6/7/2018 
Do Not Use After: 
6/6/2019 
 
 
Parental Permission Version – 1.0 
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SIGNATURES 
 
The research team has discussed this study with you and answered all of your questions.  Like any 
research, the researchers cannot predict exactly what will happen.  Once you have had enough time 
to consider whether your child should participate in this research you will document your permission 
by signature below.   
 
You will receive a copy of this signed document for your records.  
 
 
_____________________________________              
Printed Name of Research Participant 
 
 
_____________________________________             ____________  
Signature of Research Participant                              Date 
Indicating Consent or Assent  
 
 
 
 
          
 
 
____________________________________             ____________  
Signature of Parent or Legally Authorized 
           Date 
Representative*  
 
 
_______________________________________________________________ 
* If signed by a legally authorized representative, a description of such representative’s authority must 
be provided 
 
 
_____________________________________    
____________  
Signature of Individual Obtaining Consent 
 
Date