Pediatric Longitudinal Cohort Study of Chronic Pancreatitis

NCT03672422 | Completed DMC

• 2 other identifiers: 2017057093U01DK108334
• Study Type: observational
• Target: 623
• Locations: 4 countries
• Sites: 22

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.

Conditions

Pancreatitis, Chronic; Pancreatitis, Acute

Keywords

Pediatric; Pancreatitis; Chronic; Acute; Recurrent; ARP; CP; Pancreas; Children

Outcome Measures

Primary Outcomes (1)

• Length of time from progression from Acute Recurrent Pancreatitis to Chronic Pancreatitis

  Date of diagnosis of first acute pancreatitis to date of diagnosis of chronic pancreatitis presented as minimum, maximum, median number of days and no progression to chronic pancreatitis.

  3 years

Secondary Outcomes (12)

• Number of subjects with abdominal pain

  1 year

• Number of subjects with constant abdominal pain

  1 year

• Number of subjects with episodic abdominal pain

  1 year

• Number of emergency room visits subject had in the past 12 months

  1 year

• Number of emergency room visits subject had in whole life

  18 years

Study Arms (2)

Acute Recurrent Pancreatitis

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

Diagnostic Test: Blood sample; Behavioral: Patient questionnaires; Diagnostic Test: Saliva sample; Diagnostic Test: Urine sample

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).

Diagnostic Test: Blood sample; Behavioral: Patient questionnaires; Diagnostic Test: Saliva sample; Diagnostic Test: Urine sample

Interventions

Blood sample DIAGNOSTIC_TEST

Six ml of blood will be collected from patients in an EDTA tube. 2 ml saliva samples in Oragene DNA collection kits

Acute Recurrent Pancreatitis; Chronic Pancreatitis

Patient questionnaires BEHAVIORAL

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.

Acute Recurrent Pancreatitis; Chronic Pancreatitis

Saliva sample DIAGNOSTIC_TEST

2 ml saliva samples in Oragene DNA collection kits collected if no blood sample being collected.

Acute Recurrent Pancreatitis; Chronic Pancreatitis

Urine sample DIAGNOSTIC_TEST

50 ml of urine in collection container.

Acute Recurrent Pancreatitis; Chronic Pancreatitis

Eligibility Criteria

• Age: 0 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Children \<18 years of age with acute recurrent pancreatitis or chronic pancreatitis.

You may qualify if:

• \. All patients/parents must sign an informed consent and/or assent indicating that they are aware of the investigational nature of this study.
• Patients/parents must have signed an authorization for the release of their or their child's protected health information.
• 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:
• Abdominal pain compatible with AP,
• Serum amylase and/or lipase values ≥3 times upper limits of normal,
• 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:
• \. 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Aliye Uc: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (22)

Cedars-Sinai Medical Center

Beverly Hills, California, 90211, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Riley Hospital for Children Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Stead Family Children's Hospital

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University

St Louis, Missouri, 63112, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Philadelphia

Philipsburg, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Children's Health University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84108, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Sydney Children's Hospital Randwick

Randwick, New South Wales, 2031, Australia

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

Hadassah University Hospital Mt. Scopus

Jerusalem, 91240, Israel

Location

Related Publications (18)

• 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.

  PMID: 29280782 BACKGROUND

• 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.

  PMID: 29927872 BACKGROUND

• 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.

  PMID: 22357117 BACKGROUND

• 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.

  PMID: 24824361 BACKGROUND

• 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.

  PMID: 28231070 BACKGROUND

• 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.

  PMID: 27748719 BACKGROUND

• Uc A, Fishman DS. Pancreatic Disorders. Pediatr Clin North Am. 2017 Jun;64(3):685-706. doi: 10.1016/j.pcl.2017.01.010.

  PMID: 28502446 BACKGROUND

• 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.

  PMID: 27782962 RESULT

• 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.

  PMID: 28502372 RESULT

• 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.

  PMID: 26594832 RESULT

• 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.

  PMID: 27064572 RESULT

• 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.

  PMID: 29864067 RESULT

• 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.

  PMID: 27213250 RESULT

• 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.

  PMID: 29746340 RESULT

• 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.

  PMID: 28609364 RESULT

• 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.

  PMID: 28374818 RESULT

• 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.

  PMID: 25556020 RESULT

• 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.

  PMID: 26704866 RESULT

Related Links

• INSPPIRE Pediatric Pancreatitis Research Project

Biospecimen

Retention: SAMPLES WITH DNA

6 ml blood sample or 2 ml saliva sample collected 1 time. Urine 50 ml collected one time

MeSH Terms

Conditions

Pancreatitis, Chronic; Pancreatitis; Bronchiolitis Obliterans Syndrome; Recurrence

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Ying Yuan, Ph.D

  MD Anderson

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 28, 2018
• First Posted: September 14, 2018
• Study Start: June 30, 2017
• Primary Completion: August 31, 2020
• Study Completion: August 31, 2020
• Last Updated: November 6, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (18); AU (1); CA (2); IL (1)