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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03672422




Registration number
NCT03672422
Ethics application status
Date submitted
28/08/2018
Date registered
14/09/2018
Date last updated
6/11/2020

Titles & IDs
Public title
Pediatric Longitudinal Cohort Study of Chronic Pancreatitis
Scientific title
Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) CPDPC16-03 Pediatric Longitudinal Cohort Study of Chronic Pancreatitis
Secondary ID [1] 0 0
3U01DK108334
Secondary ID [2] 0 0
201705709
Universal Trial Number (UTN)
Trial acronym
INSPPIRE 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatitis, Chronic 0 0
Pancreatitis, Acute 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Observational [Patient Registry]
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Diagnosis / Prognosis - Blood sample
BEHAVIORAL - Patient questionnaires
Diagnosis / Prognosis - Saliva sample
Diagnosis / Prognosis - Urine sample

Acute Recurrent Pancreatitis - At least 2 episodes of acute pancreatitis with complete resolution of pain and a \>1 month pain-free interval between episodes.

Chronic Pancreatitis - Children with at least:

1) One irreversible structural change\* in the pancreas with or without abdominal pain +/- exocrine pancreatic insufficiency +/- diabetes.

\*irreversible structural changes:

* Ductal calculi, dilated side branches, parenchymal calcifications found in any imaging (abdominal ultrasound (abd US), magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP), computerized tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), endoscopic US (EUS).
* Ductal obstruction or stricture/dilatation/irregularities that are persistent (for \>2 months) on any imaging.
* Parenchymal atrophy, irregular contour, accentuated lobular architecture, cavities alone are not diagnostic findings for CP.
* Surgical or pancreatic biopsy specimen demonstrating histopathologic features compatible with CP (acinar atrophy, fibrosis, protein plugs, infiltration with lymphocytes, plasma cells, macrophages).


Diagnosis / Prognosis: Blood sample
Six ml of blood will be collected from patients in an EDTA tube. 2 ml saliva samples in Oragene DNA collection kits

BEHAVIORAL: Patient questionnaires
Questionnaires will be completed at the baseline and annual follow-up visits to collect data that will define the demographics of the pediatric ARP and CP cohort, describe risk factors, presence of family history of acute and chronic pancreatitis, diabetes and pancreatic cancer and assess disease burden and sequelae.

Diagnosis / Prognosis: Saliva sample
2 ml saliva samples in Oragene DNA collection kits collected if no blood sample being collected.

Diagnosis / Prognosis: Urine sample
50 ml of urine in collection container.
Intervention code [1] 0 0
Diagnosis / Prognosis
Intervention code [2] 0 0
BEHAVIORAL
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Length of time from progression from Acute Recurrent Pancreatitis to Chronic Pancreatitis
Timepoint [1] 0 0
3 years
Secondary outcome [1] 0 0
Number of subjects with abdominal pain
Timepoint [1] 0 0
1 year
Secondary outcome [2] 0 0
Number of subjects with constant abdominal pain
Timepoint [2] 0 0
1 year
Secondary outcome [3] 0 0
Number of subjects with episodic abdominal pain
Timepoint [3] 0 0
1 year
Secondary outcome [4] 0 0
Number of emergency room visits subject had in the past 12 months
Timepoint [4] 0 0
1 year
Secondary outcome [5] 0 0
Number of emergency room visits subject had in whole life
Timepoint [5] 0 0
18 years
Secondary outcome [6] 0 0
Number of hospitalizations subject had in past 12 months
Timepoint [6] 0 0
1 year
Secondary outcome [7] 0 0
Number of hospitalizations subject had in whole life
Timepoint [7] 0 0
18 years
Secondary outcome [8] 0 0
Number of school days subject missed in the last month
Timepoint [8] 0 0
30 days
Secondary outcome [9] 0 0
Number of subjects with Exocrine Pancreatic Insufficiency
Timepoint [9] 0 0
3 years
Secondary outcome [10] 0 0
Number of subjects with abnormal fasting glucose
Timepoint [10] 0 0
3 years
Secondary outcome [11] 0 0
Number of subjects with abnormal hemoglobin A1c (HbA1c)
Timepoint [11] 0 0
3 years
Secondary outcome [12] 0 0
Number of subjects with abnormal oral glucose tolerance test (OGTT)
Timepoint [12] 0 0
3 years

Eligibility
Key inclusion criteria
1. All patients/parents must sign an informed consent and/or assent indicating that they are aware of the investigational nature of this study.

2 Patients/parents must have signed an authorization for the release of their or their child's protected health information.

3 All children providing samples should fit the ARP or CP inclusion criteria defined below.

4 All children must be under 18 years of age at the time of enrollment.

Acute pancreatitis (AP): AP is defined as requiring 2 of the following:

1. Abdominal pain compatible with AP,
2. Serum amylase and/or lipase values =3 times upper limits of normal,
3. Imaging findings of AP, such as gland enlargement, acute inflammatory changes, and fluid collections.

ARP is defined as:

At least 2 episodes of acute pancreatitis with complete resolution of pain and a >1 month pain-free interval between episodes.

Chronic Pancreatitis:

Children with at least:

1. One irreversible structural change* in the pancreas with or without abdominal pain +/- exocrine pancreatic insufficiency +/- diabetes.

*irreversible structural changes:

* Ductal calculi, dilated side branches, parenchymal calcifications found in any imaging (abdominal ultrasound (abd US), magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP), computerized tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), endoscopic US (EUS).
* Ductal obstruction or stricture/dilatation/irregularities that are persistent (for >2 months) on any imaging.
* Parenchymal atrophy, irregular contour, accentuated lobular architecture, cavities alone are not diagnostic findings for CP.
* Surgical or pancreatic biopsy specimen demonstrating histopathologic features compatible with CP (acinar atrophy, fibrosis, protein plugs, infiltration with lymphocytes, plasma cells, macrophages).
Minimum age
0 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate study interventions.

Study design
Purpose
Duration
Selection
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/08/2020
Sample size
Target
Accrual to date
Final
623
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Sydney Children's Hospital Randwick - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Utah
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
United States of America
State/province [12] 0 0
Wisconsin
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Israel
State/province [15] 0 0
Jerusalem

Funding & Sponsors
Primary sponsor type
Other
Name
Aliye Uc
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
National Cancer Institute (NCI)
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The investigators will enroll a total of 628 patients under 18 years of age with ARP or CP. Included in the total are the 357patients in the INSPPIRE 1 database who are planned to be reenrolled under this protocol over the next 4 years. Patient questionnaires and physician surveys will be applied at the time of enrollment and annually thereafter as long as possible. At the first study visit after turning 18 years of age, the patient will sign the informed consent to continue in the study. Specifically, the investigators will define the demographics of the pediatric ARP and CP cohort, describe risk factors, presence of family history of acute and chronic pancreatitis, diabetes and pancreatic cancer and assess disease burden and sequelae.
Trial website
https://clinicaltrials.gov/study/NCT03672422
Trial related presentations / publications
Abu-El-Haija M, Kumar S, Quiros JA, Balakrishnan K, Barth B, Bitton S, Eisses JF, Foglio EJ, Fox V, Francis D, Freeman AJ, Gonska T, Grover AS, Husain SZ, Kumar R, Lapsia S, Lin T, Liu QY, Maqbool A, Sellers ZM, Szabo F, Uc A, Werlin SL, Morinville VD. Management of Acute Pancreatitis in the Pediatric Population: A Clinical Report From the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas Committee. J Pediatr Gastroenterol Nutr. 2018 Jan;66(1):159-176. doi: 10.1097/MPG.0000000000001715.
Abu-El-Haija M, Uc A, Werlin SL, Freeman AJ, Georgieva M, Jojkic-Pavkov D, Kalnins D, Kochavi B, Koot BGP, Van Biervliet S, Walkowiak J, Wilschanski M, Morinville VD. Nutritional Considerations in Pediatric Pancreatitis: A Position Paper from the NASPGHAN Pancreas Committee and ESPGHAN Cystic Fibrosis/Pancreas Working Group. J Pediatr Gastroenterol Nutr. 2018 Jul;67(1):131-143. doi: 10.1097/MPG.0000000000002023.
Morinville VD, Husain SZ, Bai H, Barth B, Alhosh R, Durie PR, Freedman SD, Himes R, Lowe ME, Pohl J, Werlin S, Wilschanski M, Uc A; INSPPIRE Group. Definitions of pediatric pancreatitis and survey of present clinical practices. J Pediatr Gastroenterol Nutr. 2012 Sep;55(3):261-5. doi: 10.1097/MPG.0b013e31824f1516. Erratum In: J Pediatr Gastroenterol Nutr. 2013 Apr;56(4):459. Abu-Al-Haija, Maisam [corrected to Abu-El-Haija, Maisam].
Morinville VD, Lowe ME, Ahuja M, Barth B, Bellin MD, Davis H, Durie PR, Finley B, Fishman DS, Freedman SD, Gariepy CE, Giefer MJ, Gonska T, Heyman MB, Himes R, Husain S, Kumar S, Ooi CY, Pohl JF, Schwarzenberg SJ, Troendle D, Werlin SL, Wilschanski M, Yen E, Uc A. Design and implementation of INSPPIRE. J Pediatr Gastroenterol Nutr. 2014 Sep;59(3):360-4. doi: 10.1097/MPG.0000000000000417.
Perito ER, Rhee S. Relief for Young Children With Severe Chronic Pancreatitis. J Pediatr Gastroenterol Nutr. 2017 Mar;64(3):338-339. doi: 10.1097/MPG.0000000000001509. No abstract available.
Uc A, Andersen DK, Bellin MD, Bruce JI, Drewes AM, Engelhardt JF, Forsmark CE, Lerch MM, Lowe ME, Neuschwander-Tetri BA, O'Keefe SJ, Palermo TM, Pasricha P, Saluja AK, Singh VK, Szigethy EM, Whitcomb DC, Yadav D, Conwell DL. Chronic Pancreatitis in the 21st Century - Research Challenges and Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop. Pancreas. 2016 Nov;45(10):1365-1375. doi: 10.1097/MPA.0000000000000713.
Uc A, Fishman DS. Pancreatic Disorders. Pediatr Clin North Am. 2017 Jun;64(3):685-706. doi: 10.1016/j.pcl.2017.01.010.
Gariepy CE, Heyman MB, Lowe ME, Pohl JF, Werlin SL, Wilschanski M, Barth B, Fishman DS, Freedman SD, Giefer MJ, Gonska T, Himes R, Husain SZ, Morinville VD, Ooi CY, Schwarzenberg SJ, Troendle DM, Yen E, Uc A. Causal Evaluation of Acute Recurrent and Chronic Pancreatitis in Children: Consensus From the INSPPIRE Group. J Pediatr Gastroenterol Nutr. 2017 Jan;64(1):95-103. doi: 10.1097/MPG.0000000000001446.
Giefer MJ, Lowe ME, Werlin SL, Zimmerman B, Wilschanski M, Troendle D, Schwarzenberg SJ, Pohl JF, Palermo J, Ooi CY, Morinville VD, Lin TK, Husain SZ, Himes R, Heyman MB, Gonska T, Gariepy CE, Freedman SD, Fishman DS, Bellin MD, Barth B, Abu-El-Haija M, Uc A. Early-Onset Acute Recurrent and Chronic Pancreatitis Is Associated with PRSS1 or CTRC Gene Mutations. J Pediatr. 2017 Jul;186:95-100. doi: 10.1016/j.jpeds.2017.03.063. Epub 2017 May 10. Erratum In: J Pediatr. 2018 Dec;203:468-469. doi: 10.1016/j.jpeds.2018.08.026.
Husain SZ, Morinville V, Pohl J, Abu-El-Haija M, Bellin MD, Freedman S, Hegyi P, Heyman MB, Himes R, Ooi CY, Schwarzenberg SJ, Usatin D, Uc A. Toxic-metabolic Risk Factors in Pediatric Pancreatitis: Recommendations for Diagnosis, Management, and Future Research. J Pediatr Gastroenterol Nutr. 2016 Apr;62(4):609-17. doi: 10.1097/MPG.0000000000001035.
Kumar S, Ooi CY, Werlin S, Abu-El-Haija M, Barth B, Bellin MD, Durie PR, Fishman DS, Freedman SD, Gariepy C, Giefer MJ, Gonska T, Heyman MB, Himes R, Husain SZ, Lin TK, Lowe ME, Morinville V, Palermo JJ, Pohl JF, Schwarzenberg SJ, Troendle D, Wilschanski M, Zimmerman MB, Uc A. Risk Factors Associated With Pediatric Acute Recurrent and Chronic Pancreatitis: Lessons From INSPPIRE. JAMA Pediatr. 2016 Jun 1;170(6):562-9. doi: 10.1001/jamapediatrics.2015.4955.
Lin TK, Abu-El-Haija M, Nathan JD, Palermo JP, Barth B, Bellin M, Fishman DS, Freedman SD, Gariepy CE, Giefer MJ, Gonska T, Heyman MB, Himes R, Husain SZ, Liu Q, Maqbool A, Mascarenhas M, McFerron B, Morinville VD, Ooi CY, Perito E, Pohl JF, Rhee S, Schwarzenberg SJ, Shah U, Troendle D, Werlin SL, Wilschanski M, Zimmerman MB, Lowe ME, Uc A. Pancreas Divisum in Pediatric Acute Recurrent and Chronic Pancreatitis: Report From INSPPIRE. J Clin Gastroenterol. 2019 Jul;53(6):e232-e238. doi: 10.1097/MCG.0000000000001063.
Pohl J, Morinville V, Husain SZ, Uc A. Toxic-Metabolic Risk Factors Are Uncommon in Pediatric Chronic Pancreatitis. J Pediatr Gastroenterol Nutr. 2016 Jun;62(6):e66-7. doi: 10.1097/MPG.0000000000001156. No abstract available.
Scheers I, Palermo JJ, Freedman S, Wilschanski M, Shah U, Abu-El-Haija M, Barth B, Fishman DS, Gariepy C, Giefer MJ, Heyman MB, Himes RW, Husain SZ, Lin TK, Liu Q, Lowe M, Mascarenhas M, Morinville V, Ooi CY, Perito ER, Piccoli DA, Pohl JF, Schwarzenberg SJ, Troendle D, Werlin S, Zimmerman B, Uc A, Gonska T. Recommendations for Diagnosis and Management of Autoimmune Pancreatitis in Childhood: Consensus From INSPPIRE. J Pediatr Gastroenterol Nutr. 2018 Aug;67(2):232-236. doi: 10.1097/MPG.0000000000002028.
Troendle DM, Fishman DS, Barth BA, Giefer MJ, Lin TK, Liu QY, Abu-El-Haija M, Bellin MD, Durie PR, Freedman SD, Gariepy C, Gonska T, Heyman MB, Himes R, Husain SZ, Kumar S, Lowe ME, Morinville VD, Ooi CY, Palermo J, Pohl JF, Schwarzenberg SJ, Werlin S, Wilschanski M, Zimmerman MB, Uc A. Therapeutic Endoscopic Retrograde Cholangiopancreatography in Pediatric Patients With Acute Recurrent and Chronic Pancreatitis: Data From the INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) Study. Pancreas. 2017 Jul;46(6):764-769. doi: 10.1097/MPA.0000000000000848.
Scheers I, Palermo JJ, Freedman S, Wilschanski M, Shah U, Abu-El-Haija M, Barth B, Fishman DS, Gariepy C, Giefer MJ, Heyman MB, Himes RW, Husain SZ, Lin TK, Liu Q, Lowe M, Mascarenhas M, Morinville V, Ooi CY, Perito ER, Piccoli DA, Pohl JF, Schwarzenberg SJ, Troendle D, Werlin S, Zimmerman B, Uc A, Gonska T. Autoimmune Pancreatitis in Children: Characteristic Features, Diagnosis, and Management. Am J Gastroenterol. 2017 Oct;112(10):1604-1611. doi: 10.1038/ajg.2017.85. Epub 2017 Apr 4.
Schwarzenberg SJ, Bellin M, Husain SZ, Ahuja M, Barth B, Davis H, Durie PR, Fishman DS, Freedman SD, Gariepy CE, Giefer MJ, Gonska T, Heyman MB, Himes R, Kumar S, Morinville VD, Lowe ME, Nuehring NE, Ooi CY, Pohl JF, Troendle D, Werlin SL, Wilschanski M, Yen E, Uc A. Pediatric chronic pancreatitis is associated with genetic risk factors and substantial disease burden. J Pediatr. 2015 Apr;166(4):890-896.e1. doi: 10.1016/j.jpeds.2014.11.019. Epub 2014 Dec 30.
Ting J, Wilson L, Schwarzenberg SJ, Himes R, Barth B, Bellin MD, Durie PR, Fishman DS, Freedman SD, Gariepy CE, Giefer MJ, Gonska T, Husain SZ, Kumar S, Morinville VD, Lowe ME, Ooi CY, Pohl JF, Troendle D, Usatin D, Werlin SL, Wilschanski M, Heyman MB, Uc A. Direct Costs of Acute Recurrent and Chronic Pancreatitis in Children in the INSPPIRE Registry. J Pediatr Gastroenterol Nutr. 2016 Mar;62(3):443-9. doi: 10.1097/MPG.0000000000001057.
Public notes

Contacts
Principal investigator
Name 0 0
Ying Yuan, Ph.D
Address 0 0
MD Anderson
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03672422