PROOF: Pancreatitis-associated Risk Of Organ Failure (PROOF)

This is a prospective case control study that compares the initial immune response with severity and outcome in patients with acute pancreatitis.

Study Overview

• Status: Completed
• Conditions: Pancreatitis; Organ Failure, Multiple

Detailed Description

This is a prospective case control study that compares the initial immune response with severity and outcome in patients with acute pancreatitis. Therefore, the investigators aim to determine whether etiology of acute pancreatitis, segregates with candidate genetic polymorphisms and their m-RNA expression, as well as whether functional polymorphisms in inflammation regulating genes predict a more severe outcome in acute pancreatits. The investigators anticipate that based on our results that we will provide a more accurate predictor of the clinical course of acute pancreatits and help direct more aggressive or cytokine specific treatment of patients at greater risk of a more severe form of the disease.

• Study Type: Observational
• Enrollment (Actual): 723

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Both males and females, over 1 year of age.

Description

Inclusion Criteria:

• Inclusion criteria for Subjects (all three) Males and females of 16 years of age and older. Body weight at least 40kg

Diagnosis of acute pancreatitis by both: Abdominal pain or abdominal localizing signs AND Elevated amylase levels by at-least three times the upper limit of normal and/or elevated lipase levels by at-least three times the upper limit of normal (25, 26). Acute pancreatitis must be defined by 2 of the 3 following criteria:

• Serum amylase or lipase elevated greater than 3X upper limit of normal
• epigastric acute pancreatitis pain
• abdominal imaging studies demonstrating pancreatic edema, peripancreatic fat stranding or complications or acute pancreatitis Willingness to participate in the study and sign the informed consent. (Children and subjects who are cognitively impaired for temporary reasons as mentioned in the section 4.7 of this protocol will require a representative to sign the informed consent).

Inclusion criteria for Controls (all three) Males and females of 18 years of age and older. a. Unrelated family member or a friend of the subject or a patient having blood drawn in general medicine outpatient clinic, without a history of pancreatitis, OR Willingness to participate in the study and sign the informed consent.

Additional Inclusion Criteria for subjects with a previous attack of acute pancreatitis:

age criteria as defined above.

- Previous severe attack of severe acute pancreatitis requiring a ICU stay of at least 48 hours or evidence of pancreatic necrosis on computerized tomography.

Willingness to participate and sign informed consent

Exclusion Criteria:

• Exclusion Criteria for Subjects:

Persons unwilling to sign the informed consent Disorientation secondary to irreversible organic brain damage. Mean corpuscular volume (MCV) of less than 77 in all children of 18 years or younger.

Blood transfusion within one week of enrollment Chronic Pancreatitis History of pancreatic cancer History of cancer requiring chemotherapy or radiation within the past 1 year History of organ transplant Subject is a prisoner Pancreatitis due to multiple trauma or surgical complications

Exclusion criteria for Controls:

Persons unwilling to sign the informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Subjects with acute pancreatitis
Subjects with previous attack
Controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe Acute Pancreatitis (defined as persistent organ failure)	To compare the initial immune response in patients who developed mild vs. severe disease. To determine whether functional polymorphisms in inflammation regulating genes predicts a more severe outcome in acute pancreatitis.	1 year

Collaborators and Investigators

• Sponsor: University of Pittsburgh

Publications and helpful links

General Publications

• Langmead C, Lee PJ, Paragomi P, Greer P, Stello K, Hart PA, Whitcomb DC, Papachristou GI. A Novel 5-Cytokine Panel Outperforms Conventional Predictive Markers of Persistent Organ Failure in Acute Pancreatitis. Clin Transl Gastroenterol. 2021 May 6;12(5):e00351. doi: 10.14309/ctg.0000000000000351.
• Komara NL, Paragomi P, Greer PJ, Wilson AS, Breze C, Papachristou GI, Whitcomb DC. Severe acute pancreatitis: capillary permeability model linking systemic inflammation to multiorgan failure. Am J Physiol Gastrointest Liver Physiol. 2020 Nov 1;319(5):G573-G583. doi: 10.1152/ajpgi.00285.2020. Epub 2020 Sep 2.
• Dugum M, Gougol A, Paragomi P, Gao X, Matta B, Yazici C, Tang G, Greer P, Pothoulakis I, O'Keefe SJD, Whitcomb DC, Yadav D, Papachristou GI. Association of Dietary Habits with Severity of Acute Pancreatitis. Curr Dev Nutr. 2018 Oct 8;2(12):nzy075. doi: 10.1093/cdn/nzy075. eCollection 2018 Dec.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2008
• Primary Completion (Actual): July 5, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: February 2, 2017
• First Submitted That Met QC Criteria: March 3, 2017
• First Posted (Actual): March 9, 2017

Study Record Updates

• Last Update Posted (Actual): March 5, 2021
• Last Update Submitted That Met QC Criteria: March 4, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Shock; Pancreatic Diseases; Pancreatitis; Multiple Organ Failure
• Other Study ID Numbers: PRO08010374

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: If shared, all individual identifiers will be removed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No