Exocrine-Endocrine Pancreatic Crosstalk: Precision Pathways to Reframe Diabetes Pathophysiology (EXPAND)

June 22, 2026 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

The EXPAND study is a prospective observational study designed to investigate the biological mechanisms underlying the heterogeneity of type 2 diabetes and related metabolic disorders.

The study will enroll adults with and without pancreatic disease, including patients undergoing pancreatic surgery, individuals with chronic pancreatitis, subjects at high risk of type 2 diabetes, and patients with newly diagnosed type 2 diabetes. Clinical, metabolic, imaging, genetic, microbiome, and molecular data will be integrated to identify distinct metabolic endotypes and to investigate the interactions between the exocrine pancreas, endocrine pancreas, and adipose tissue. The ultimate goal is to improve the understanding of diabetes pathophysiology and support the development of precision medicine approaches.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Type 2 diabetes mellitus is a heterogeneous disease characterized by substantial variability in pathophysiological mechanisms, disease progression, and clinical outcomes. Current clinical classifications do not fully capture the biological complexity underlying metabolic dysfunction.

The EXPAND (Exocrine-Endocrine Pancreatic Axis in Diabetes) study is a prospective observational study aimed at identifying and characterizing metabolic endotypes through the integration of clinical, metabolic, imaging, genetic, microbiome, and multi-omic data. The study is based on the hypothesis that interactions among the exocrine pancreas, endocrine pancreas, and adipose tissue contribute to beta-cell dysfunction and metabolic heterogeneity.

Approximately 440 participants will be enrolled across five predefined cohorts: patients undergoing pancreatic resection for pancreatic diseases, patients with chronic or previous pancreatitis, individuals at increased risk of type 2 diabetes, and subjects with newly diagnosed type 2 diabetes.

Participants will undergo detailed metabolic phenotyping including oral glucose tolerance tests, hyperglycemic/euglycemic clamp studies, laboratory assessments, magnetic resonance imaging-based body fat quantification, dietary assessment, genetic analyses, microbiome profiling, and biomarker measurements. For surgical cohorts, pancreatic and adipose tissue samples obtained during clinically indicated surgery will also be analyzed.

Unsupervised clustering and archetype analysis approaches will be used to identify metabolic endotypes. Associations between endotypes and clinical, metabolic, imaging, histopathological, genetic, and molecular characteristics will be explored. Longitudinal analyses in surgical cohorts will evaluate metabolic changes following pancreatic resection.

The results are expected to improve the understanding of diabetes pathophysiology and facilitate the development of biomarker-driven precision medicine strategies.

Study Type

Observational

Enrollment (Estimated)

440

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Participants will be recruited from patients receiving care at Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy). The study population includes adults with and without pancreatic disease, including individuals undergoing pancreatic resection, patients with chronic or previous pancreatitis, subjects at increased risk of type 2 diabetes mellitus, and individuals with newly diagnosed type 2 diabetes mellitus. Participants will be consecutively enrolled from the Departments of Endocrinology, Diabetology, Gastroenterology, and Pancreatic Surgery according to the predefined eligibility criteria.

Description

Inclusion Criteria:

  • Adults aged 20 to 78 years.
  • Ability and willingness to provide written informed consent.
  • Eligibility for one of the study cohorts:
  • Individuals undergoing pancreatectomy for non-endocrine pancreatic disease.
  • Individuals with pancreatic ductal adenocarcinoma undergoing pancreatectomy.
  • Individuals with chronic pancreatitis or a previous episode of acute pancreatitis.
  • Individuals at increased risk of type 2 diabetes mellitus, including impaired fasting glucose and/or impaired glucose tolerance.
  • Individuals with newly diagnosed type 2 diabetes mellitus.
  • Ability to undergo study-related metabolic assessments and sample collection procedures.

Exclusion Criteria:

  • Age <20 years or >78 years.
  • Inability or unwillingness to provide informed consent.
  • Pregnancy or breastfeeding.
  • Diagnosis of type 1 diabetes mellitus.
  • Participation in another interventional clinical trial involving an investigational medicinal product within 30 days before enrollment.
  • Clinical conditions that preclude completion of the planned metabolic assessments.
  • Inability to comply with study procedures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Pancreatic Surgery for Non-Endocrine Pancreatic Disease
Adults undergoing partial or total pancreatectomy for non-endocrine pancreatic disease. Participants will undergo clinical evaluation, metabolic phenotyping, imaging assessments, biomarker measurements, gut microbiome profiling from stool samples, and Genetic Risk Score determination. Pancreatic and adipose tissue specimens obtained during clinically indicated surgery may be analyzed for histopathological, molecular, and multi-omic studies.
Pancreatic Ductal Adenocarcinoma Undergoing Pancreatectomy
Adults with pancreatic ductal adenocarcinoma undergoing partial or total pancreatectomy. Participants will undergo clinical evaluation, metabolic phenotyping, imaging assessments, biomarker measurements, gut microbiome profiling from stool samples, and Genetic Risk Score determination. Pancreatic and adipose tissue specimens obtained during clinically indicated surgery may be analyzed for histopathological, molecular, and multi-omic studies.
Chronic or Previous Pancreatitis
Adults with chronic pancreatitis or a previous episode of acute pancreatitis. Participants will undergo clinical evaluation, metabolic phenotyping, imaging assessments, biomarker measurements, gut microbiome profiling from stool samples, and Genetic Risk Score determination.
Individuals at Risk for Type 2 Diabetes
Adults at increased risk of type 2 diabetes, including individuals with impaired fasting glucose and/or impaired glucose tolerance, without exocrine pancreatic disease. Participants will undergo clinical evaluation, metabolic phenotyping, imaging assessments, biomarker measurements, gut microbiome profiling from stool samples, and Genetic Risk Score determination.
Newly Diagnosed Type 2 Diabetes
Adults with newly diagnosed type 2 diabetes mellitus. Participants will undergo clinical evaluation, metabolic phenotyping, imaging assessments, biomarker measurements, gut microbiome profiling from stool samples, and Genetic Risk Score determination.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification and Characterization of Metabolic Endotypes
Time Frame: At baseline and during study assessments up to 60 months
Identification and characterization of physiological endotypes of glucose metabolism using unsupervised clustering and archetype analysis integrating metabolic phenotyping, imaging, and biological/multi-omic variables.
At baseline and during study assessments up to 60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

  • Principal Investigator: Teresa Mezza, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

November 1, 2029

Study Completion (Estimated)

September 1, 2031

Study Registration Dates

First Submitted

June 22, 2026

First Submitted That Met QC Criteria

June 22, 2026

First Posted (Actual)

June 26, 2026

Study Record Updates

Last Update Posted (Actual)

June 26, 2026

Last Update Submitted That Met QC Criteria

June 22, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 27477

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pancreatic Neoplasms

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Peru

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe