French National Cohort of Patients With PRSS1 Mutations (PARADISIO 1)

The diagnosis of hereditary pancreatitis (PH) is based on a genetic criterion - detection of a mutation in the PRSS1 gene or on a genealogical criterion - the presence of chronic pancreatitis in at least 2 first-degree relatives or at least 3 relatives in the second degree, in the absence of other identified predisposing factors (notably chronic alcohol consumption). It is now recommended to seek PH in cases of pancreatitis of unknown origin in a young patient or with a family history.

In this study, patients carrying a PRSS1 mutation will be identified from the patient lists of the three French genetics laboratories (Brest University Hospital, Cochin-Paris University Hospital, Lille University Hospital) carrying out PRSS1 gene analysis. Patients will be included by the doctors currently treating them.

The aim of the study is to assess the incidence of pancreatic adenocarcinoma in the cohort and describe the natural history of hereditary pancreatitis linked to a mutation in PRSS1.

Study Overview

• Status: Recruiting
• Conditions: Hereditary Pancreatitis; PRSS1 Gene Mutation
• Intervention / Treatment: Other: collecting their health data from their medical file and completing questionnaires.

Detailed Description

The diagnosis of hereditary pancreatitis (HP) is based on a genetic criterion - identification of a mutation in the PRSS1 gene - or a genealogical criterion - the presence of chronic pancreatitis in at least 2 first-degree relatives or at least 3 second-degree relatives, in the absence of other identified predisposing factors (in particular chronic alcohol consumption). It is now recommended to look for PH in cases of pancreatitis of unknown origin in young patients or those with a family history.

The first mutation in the PRSS1 gene, R122H, was described in 1996. Today, >100 PRSS1 variants are known. Of these, 26 variants are considered 'pathological' and 51 'benign', with the other variants having a less well-defined clinical outcome. PH is a rare cause of pancreatitis (< 1%). Its prevalence in France is estimated at 0.3/100,000 people.

Because of its rarity, there are few studies to decipher this disease. Fewer than 1,000 patients are affected in France. In practice, there is great variability in the phenotypic expression of mutations, even for a similar mutation in the same family. There is a lack of scientific knowledge, which means that patients with PH cannot be treated optimally.

In this study, patients carrying a PRSS1 mutation will be identified from the patient lists of the three French genetics laboratories (Brest University Hospital, Cochin-Paris University Hospital, Lille University Hospital) carrying out PRSS1 gene analysis. Patients will be included by the doctors currently treating them. The cohort will be updated as new patients are diagnosed, and the completeness of the cases recorded in the database will be checked every 5 years. Patients are seen annually as part of their care, so medical data can be collected at each visit. Questionnaires will be administered every 5 years during a care visit.

The aim of the study is to assess the incidence of pancreatic adenocarcinoma in the cohort and describe the natural history of hereditary pancreatitis linked to a mutation in PRSS1.

• Study Type: Observational
• Enrollment (Estimated): 800

Contacts and Locations

• Study Contact: Name: Claude FEREC
• Study Contact Backup: Name: Vinciane REBOURS; Phone Number: +33 1 40 87 52 15; Email: vinciane.rebours@aphp.fr

Study Locations

• France
  • Clichy-sous-Bois, France
    • Recruiting
    • REBOURS
    • Contact: REBOURS Vinciane; Phone Number: 33 140875215; Email: vinciane.rebours@aphp.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Any patient, symptomatic or not, carrying a PRSS1 mutation detected in one of the 3 genetic laboratories carrying out this targeted genetic analysis in France. Children may be included in this study with the consent of their parents. People under guardianship or curatorship may also be included with the agreement of their guardian or curator.

Description

Inclusion Criteria:

• Being a carrier of a known genetic mutation in the PRSS1 gene coding for cationic trypsinogen
• Be followed in one of the participating centers

Exclusion Criteria:

• Opposition to data collection, expressed by the patient or one of their legal representatives

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the incidence of pancreatic adenocarcinoma	Occurrence of pancreatic adenocarcinoma	20 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe the natural history of hereditary pancreatitis linked to a PRSS1 mutation 1/2.	Occurrence of endocrine pancreatic insufficiency	20 years
Describe the natural history of hereditary pancreatitis linked to a PRSS1 mutation 2/2.	Occurrence of exocrine pancreatic insufficiency	20 years
incidence of pancreatic adenocarcinoma in carriers of a PRSS1 mutation to the incidence of pancreatic cancer in the general population in France, estimated from French and international digestive cancer registers 1/2.	Occurrence of endocrine pancreatic insufficiency	20 years
incidence of pancreatic adenocarcinoma in carriers of a PRSS1 mutation to the incidence of pancreatic cancer in the general population in France, estimated from French and international digestive cancer registers.2/2	Occurrence of exocrine pancreatic insufficiency	20 years
Risk factors associated with progression to adenocarcinoma 1/2	type of PRSS1 mutation.	20 years
Risk factors associated with progression to adenocarcinoma 2/2	comorbidity	20 years
Clinical phenotype of patients	Collection of clinical characteristics (phenotype) of patients with hereditary pancreatitis.	20 years
Establish a phenotype-genotype correlation:	Assessment of the association between identified genetic mutations and clinical phenotype	20 years
Calculate the crude and cumulative incidence of exocrine and endocrine pancreatic insufficiency.	Occurrence of endocrine pancreatic insufficiency	20 years
Calculate the crude and cumulative incidence of exocrine and endocrine pancreatic insufficiency.	Occurrence of exocrine pancreatic insufficiency	20 years
Evaluate the quality of life of patients with hereditary pancreatitis	Assessment of patients' quality of life using quality of life questionnaires: SF-36 a	20 years
Evaluate the quality of life of patients with hereditary pancreatitis	Pain assessment: Izbicki Pain Score	20 years
Evaluate the quality of life of patients with hereditary pancreatitis	Pain assessment: COMPAT-SF Questionnaire	20 years
Evaluate the quality of life of patients with hereditary pancreatitis, particularly the impact of pain.	Pain assessment: Izbicki Pain Score	20 years
Evaluate the quality of life of patients with hereditary pancreatitis, particularly the impact of pain.	Pain assessment: COMPAT-SF Questionnaire	20 years
Evaluate the quality of life of patients with hereditary pancreatitis, particularly the impact of pain.	Assessment of patients' quality of life using quality of life questionnaires: EQ-5D	20 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Vinciane REBOURS, APHP

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2024
• Primary Completion (Estimated): November 30, 2044
• Study Completion (Estimated): December 31, 2044

Study Registration Dates

• First Submitted: February 2, 2026
• First Submitted That Met QC Criteria: February 9, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: hereditary pancreatitis, mutation
• Additional Relevant MeSH Terms: Hereditary pancreatitis
• Other Study ID Numbers: APHP240988; 2024-A01666-41 (Other Identifier: IDRCB)

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