IPEX Study: Pancreatic Exocrine Insufficiency as a Functional Marker of Disease Progression in Patients With IPMN (IPEX)

IPEX Study: Pancreatic Exocrine Insufficiency as a Functional Marker of Disease Progression in Patients With IPMN Under Surveillance

Intraductal Papillary Mucinous Neoplasms (IPMN) are pancreatic cystic neoplasms managed through imaging-based surveillance focused on oncologic risk. However, IPMN pathophysiology includes ductal obstruction by mucin, chronic ductal hypertension, and progressive parenchymal atrophy, mechanisms that may lead to pancreatic exocrine insufficiency (PEI).

PEI is a maldigestion syndrome typically associated with chronic pancreatitis, pancreatic cancer, and pancreatic surgery, but it has never been systematically investigated in patients with IPMN under surveillance.

The IPEX study is a multicenter prospective observational cohort study designed to evaluate whether PEI is prevalent in IPMN patients and whether it correlates with morphologic disease progression. The study also evaluates the potential role of PEI as a functional marker complementary to imaging criteria in IPMN surveillance.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Exocrine Insufficiency; Intraductal Papillary Mucinous Neoplasms

Detailed Description

progression in patients diagnosed with branch-duct, main-duct, or mixed-type IPMN undergoing routine surveillance.

PEI will be assessed using a composite clinical-biochemical definition based on fecal elastase-1 (FE-1) levels and standardized clinical evaluation through a pancreatology visit and PEI Symptom Score (PSS).

IPMN progression will be defined according to the development of worrisome features (WF), high-risk stigmata (HRS), need for intensified surveillance, referral to surgery, histologic high-grade dysplasia/carcinoma, or diagnosis of concomitant pancreatic ductal adenocarcinoma.

The study does not introduce any intervention beyond standard care and aims to determine whether PEI represents a marker of functional pancreatic deterioration associated with IPMN evolution.

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Giacomo Deiro, MD; Phone Number: +393489818794; Email: giacomo.deiro@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing routine surveillance for IPMN at participating centers.

Description

Inclusion Criteria:

• Age ≥18 years
• Diagnosis of BD-IPMN, MD-IPMN, or mixed IPMN
• Under active imaging surveillance
• Signed informed consent

Exclusion Criteria:

• Prior pancreatic surgery
• Chronic pancreatitis
• Known pancreatic ductal adenocarcinoma at baseline
• Other established causes of PEI unrelated to IPMN

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

IPMN; This study includes a single prospective observational cohort of adult patients (≥18 years) with a diagnosis of intraductal papillary mucinous neoplasm (IPMN)-including branch-duct, main-duct, or mixed-type. Participants are managed according to standard-of-care IPMN surveillance protocols (MRI/MRCP ± EUS), with no mandated interventional treatment. In parallel, patients undergo a structured pancreatology assessment to evaluate pancreatic exocrine function. The exposure of interest is pancreatic exocrine insufficiency (PEI), defined using a composite clinical-biochemical criterion based on fecal elastase-1 (FE-1) levels and standardized clinical and nutritional parameters. No experimental intervention is administered; initiation of pancreatic enzyme replacement therapy (PERT), when clinically indicated, is recorded but not protocol-driven.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between clinically relevant PEI and IPMN progression during follow-up	Clinically relevant PEI defined as: FE-1 <100 µg/g OR; FE-1 100-200 µg/g plus ≥1 clinical criterion IPMN progression defined by WF/HRS development, surgical referral, or histologic progression	Day 1 and after 6 and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence and incidence of PEI in IPMN patients		Day 1 and after 6 and 12 months
Association between imaging parameters (MPD diameter, parenchymal atrophy) and PEI		Day 1 and after 6 and 12 months
Time-to-progression stratified by PEI status		Day 1 and after 6 and 12 months
Nutritional impact of PEI	Weight loss	Day 1 and after 6 and 12 months
Incremental predictive value of PEI beyond imaging criteria		Day 1 and after 6 and 12 months

Collaborators and Investigators

• Sponsor: A.O.U. Città della Salute e della Scienza
• Investigators: Principal Investigator: Giacomo Deiro, MD, A.O.U. Città della Salute e della Scienza

Publications and helpful links

General Publications

• Tanaka M, Fernandez-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, Kimura W, Levy P, Pitman MB, Schmidt CM, Shimizu M, Wolfgang CL, Yamaguchi K, Yamao K; International Association of Pancreatology. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012 May-Jun;12(3):183-97. doi: 10.1016/j.pan.2012.04.004. Epub 2012 Apr 16.
• Ohtsuka T, Fernandez-Del Castillo C, Furukawa T, Hijioka S, Jang JY, Lennon AM, Miyasaka Y, Ohno E, Salvia R, Wolfgang CL, Wood LD. International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas. Pancreatology. 2024 Mar;24(2):255-270. doi: 10.1016/j.pan.2023.12.009. Epub 2023 Dec 28.
• Dominguez-Munoz JE, Vujasinovic M, de la Iglesia D, Cahen D, Capurso G, Gubergrits N, Hegyi P, Hungin P, Ockenga J, Paiella S, Perkhofer L, Rebours V, Rosendahl J, Salvia R, Scheers I, Szentesi A, Bonovas S, Piovani D, Lohr JM; European PEI Multidisciplinary Group. European guidelines for the diagnosis and treatment of pancreatic exocrine insufficiency: UEG, EPC, EDS, ESPEN, ESPGHAN, ESDO, and ESPCG evidence-based recommendations. United European Gastroenterol J. 2025 Feb;13(1):125-172. doi: 10.1002/ueg2.12674. Epub 2024 Dec 5.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 16, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: pancreatic exocrine insufficiency; Intraductal Papillary Mucinous Neoplasms; Functional Marker
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Exocrine Pancreatic Insufficiency
• Other Study ID Numbers: IPEX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data obtained through this study may be provided to qualified researchers with academic interest in the topic. Data shared will be coded, with no PHI included. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party.
• IPD Sharing Time Frame: Data will be available beginning 6-12 months after publication of the primary results and for up to 5 years thereafter.
• IPD Sharing Access Criteria: Data sharing will require a formal data-sharing agreement and compliance with applicable data protection laws (e.g., GDPR).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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