National Database on Primary Biliary Cholangitis

Recruiting

• Conditions: Primary Biliary Cholangitis
• Interventions: Other: Clinical information

• Registration Number: NCT05151809
• Lead Sponsor: University of Milano Bicocca

Brief Summary

Primary biliary cholangitis (PBC) is a rare, autoimmune, cholestatic liver disease. No data about the disease epidemiology exist in Italy. Therefore this study aims to develop a national PBC patient database linked to a biological sample storage.

Detailed Description

Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by chronic inflammation of the intrahepatic bile ducts, causing progressive ductopenia, cholestasis, and if not effectively treated, leading to fibrosis, cirrhosis and liver failure. Nowadays almost all patients with PBC are diagnosed at an early disease stage and receive treatment with ursodeoxycholic acid (UDCA) which is currently the only drug approved for the treatment of patients with PBC. However, approximately 20% to 30% (up to \>50% in patients presenting under the age of 40 years) still does not have a benefit from UDCA and has a reduced prognosis as compared to healthy individuals. Major steps forwards in the field of PBC have been done in the last decade, however there are still significant areas of unmet clinical need in PBC: the lack of knowledge on etiopathogenesis; a poor understanding of disease sub-phenotypes; the lack of biomarkers of disease progression that allow risk stratification needed in clinical management and trials design, among the others. In the current evolving research landscape with the availability of the -omics technologies generating libraries of genome-wide data, metabolomics and proteomics data, among the others, the prospects of discovering the gene and molecular underpinnings of PBC are more promising than ever. Scientists envision an era of "personalized medicine" when more and more people will obtain their own genetic and metabolic maps, enabling them to identify their status as carriers of specific risk profiles.

Based on these premises, the current project aims to build up a research, nation-wide infrastructure (around 60 Italian participating centres will be involved) to study the biology of PBC and, in particular, to explore why a significant group of, typically young patients fail primary therapy with UDCA, placing them at risk of developing progressive disease and needing liver transplantation (LT). The investigators will recruit patients and organise the collection of important clinical information and laboratory investigation, together with biological samples. Data will be collected in the form of electronic Case Report Forms (REDCap cloud) that will be completed by clinicians at baseline and thereafter on an annual basis. The clinical information will allow us to identify patients' clinical profiles. The biological samples will allow to understand key aspects of people's make up, including patient genes and the way their immune system works, and the differences in make up between people with different clinical phenotypes.

This research infrastructure would represent an invaluable resource for successful translational research in this field. Specifically, it would serve investigators conducting research; clinicians treating patients; epidemiologists gathering demographic data; and the drug and device industry seeking new markets. It also can represent a necessary infrastructure for the implementation of the European Reference Networks (ERN) for rare diseases, main pillars of the current EU policy framework on National Plans for research and development. The Italian PBC database would also be crucial for drug development, specifically to assess the feasibility of clinical trials, to facilitate the planning of appropriate clinical trials, to support the enrolment of patients and to assess the impact of new interventions.

Study Timeline

• Study Start: 2019-09-19
• Study First Submitted: 2021-11-15
• Study First Submitted QC: 2021-11-25
• Study First Posted: 2021-12-09
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-30
• Last Update Posted: 2023-03-31
• Primary Completion: 2029-01-24
• Study Completion: 2029-01-24

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 6000

Inclusion Criteria

All PBC patients living in Italy and aged at least 18 years can be included in the database. According to well-established criteria, PBC is diagnosed in subjects who fulfill two of the three of following criteria:

• elevated alkaline phosphatase and /or GGT;
• positive anti-mitochondrial autoantibodies (titer ≥ 1:40) or PBC-specific antinuclear antibodies (gp-210 and sp100);
• characteristic histological features of florid bile ducts lesions and granulomatous lesion.

Exclusion Criteria

The patient has explicitly declared his/her unwillingness to participate to the study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PBC population residing in Italy	Clinical information	All PBC patients living in Italy and aged at least 18 years can be included in the database. According to well-established criteria, PBC is diagnosed in subjects who fulfill two of the three of following criteria: 1. elevated alkaline phosphatase and /or GGT; 2. positive anti-mitochondrial autoantibodies (titer ≥ 1:40) or PBC-specific antinuclear antibodies (gp-210 and sp100); 3. characteristic histological features of florid bile ducts lesions and granulomatous lesion.

Primary Outcome Measures

Name	Time	Method
Phenotypes and sub-phenotypes of PBC Italian patients	Overall duration of the study (10 years)	Identify and define distinct phenotypes and sub-phenotypes of PBC patients at higher risk of disease progression.

Secondary Outcome Measures

Name	Time	Method
Response to UDCA therapy	Overall duration of the study (10 years)	Defined as Alkaline Phosphatase Level\<1 x upper limit of normal. The investigators will fit a multivariate analysis using logistic regression using baseline variables.
Safety and long-term efficacy of novel therapies	Overall duration of the study (10 years)	The investigators will evaluate prospectively laboratory investigation and the treatment response to novel therapies that are entering the clinical practice, e.g. obeticholic acid, fibrates.
Identification of factors influencing the progression of PBC	Overall duration of the study (10 years)	The investigators will calculate the time from the diagnosis of PBC to an event (liver decompensation, liver transplantation or death). They will then fit a multivariate analysis using Cox's proportional hazards regression model of diverse explanatory variables available at baseline.

Trial Locations

Locations (55)

UO di Epatologia, Universita' di Roma Tor Vergata; 🇮🇹 Roma, Italy

Ospedali riuniti di Ancona; 🇮🇹 Ancona, Italy

UO di gastroenterologia, Asst Papa Giovanni XXIII; 🇮🇹 Bergamo, Italy

Presidio Ospedaliero di Faenza- UO Medicina Interna; 🇮🇹 Faenza, Italy

Day Hospital e Ambulatorio di Epatoogia e Nutrizione Clinica, Fondazione Evangelica Villa Betania, Ospedale generale di Zona; 🇮🇹 Napoli, Italy

UO di Medicina Interna, Azienda Ospedaliera di Padova; 🇮🇹 Padova, Italy

UO di gastroenterologia, Spedali civili di Brescia; 🇮🇹 Brescia, Italy

UO di fisiopatologia digestiva, Azienda Ospedaliera Universitaria Mater Domini; 🇮🇹 Catanzaro, Italy

Centro C.U.R.E. Centro Universitario per la ricerca e la Cura delle Malattie Epatiche; 🇮🇹 Foggia, Italy

Ambulatorio di Malattie del Fegato, U.O. Medicina, ASST Valle Olona, Presidio di Gallarate; 🇮🇹 Gallarate, Italy

UO di epatologia clinica e biomolecolare, Università degli studi di Messina; 🇮🇹 Messina, Italy

Policlinico S.Orsola Malpighi- Ambulatorio di epatologia e gestione trapianto epatico; 🇮🇹 Bologna, Italy

Ospedale IRCCS Saverio De Bellis- UOC di Gastroenterologia 1; 🇮🇹 Castellana Grotte, Italy

UO epatologia Ospedale Garibaldi; 🇮🇹 Catania, Italy

UO di gastroenterologia, Ospedale Valduce; 🇮🇹 Como, Italy

Azienda Socio Sanitaria Territoriale (ASST) di Cremona- UO Medicina Interna - Ambulatori di Epatologia; 🇮🇹 Cremona, Italy

UO Clinica Medica, Azienda Ospedaliera Universitaria Careggi Firenze; 🇮🇹 Firenze, Italy

University of Milano-Bicocca; 🇮🇹 Milan, Italy

AOU di Modena- U.O. Gastroenterologia; 🇮🇹 Modena, Italy

UO epatologia, AOU pisana Cisanello; 🇮🇹 Pisa, Italy

Università degli studi di Salerno; 🇮🇹 Salerno, Italy

SSD Epatologia, Fondazione Casa Sollievo della Sofferenza; 🇮🇹 San Giovanni Rotondo, Italy

Azienda Ospedale Universitaria di Sassari- UOC Medicina Interna; 🇮🇹 Sassari, Italy

SOS di DPT Epatologia e Trapianti di Fegato, ASU FC; 🇮🇹 Udine, Italy

A.O.U. Consorziale - Policlinico Bari- UO Gastroenterologia; 🇮🇹 Bari, Italy

Centro Medicina del Viaggiatore e delle Migrazioni, ASP Catanzaro, Presìdio Ospedaliero "Giovanni Paolo II"; 🇮🇹 Lamezia Terme, Italy

Policlinico di Milano; 🇮🇹 Milano, Italy

Struttura Complessa di Medicina ad Indirizzo Metabolico Nutrizionale, Dipartimento Ospedaliero di Medicina Interna; 🇮🇹 Modena, Italy

UO gastroenterologia, Policlinico Paolo Giaccone; 🇮🇹 Palermo, Italy

Malattie infettive ed epatologia, Azienda ospedaliero universitaria di Parma; 🇮🇹 Parma, Italy

S.C. Gastroenterologia, Azienda Ospedaliero-Universitaria Molinette; 🇮🇹 Torino, Italy

Ospedale regionale Ca' Foncello di Treviso- Unità operativa complessa di Gastroenterologia; 🇮🇹 Treviso, Italy

Policlinico Universitario Fondazione Agostino Gemelli- UO di medicina interna; 🇮🇹 Roma, Italy

Gastroenterologia, fisiopatologia e endoscopia digestiva, Azienda sanitaria dell'alto adige; 🇮🇹 Bolzano, Italy

Policlinico S. Orsola Malpighi- UO Medicina Interna; 🇮🇹 Bologna, Italy

Unità epatologica ed ecografia internistica a valenza dipartimentale, Fondazione Ospedaliera Poliambulanza; 🇮🇹 Brescia, Italy

UO epatologia, Azienda ospedaliero università di Cagliari Policlinico universitario Monserrato; 🇮🇹 Cagliari, Italy

UO Clinica Gastroenterologica, Policlinico San Martino; 🇮🇹 Genova, Italy

UO di epatologia, Ospedale Niguarda Ca' Granda; 🇮🇹 Milano, Italy

UO di Epatologia, Ospedale San Giuseppe; 🇮🇹 Milano, Italy

UO epatologia, Istituto scientifico universitario San Raffaele; 🇮🇹 Milano, Italy

Ospedale policlinico Federico II di Napoli; 🇮🇹 Napoli, Italy

UO medicina ed epatologia, Ospedale maggiore della carità; 🇮🇹 Novara, Italy

Day Hospital Internistico e ambulatorio di Epatologia, ASL Pescara; 🇮🇹 Pescara, Italy

S.C. Gastroenterologia, Ospedale di Pordenone, AS FO; 🇮🇹 Pordenone, Italy

UO di Gastroenterologia, Policlinico Umberto I; 🇮🇹 Roma, Italy

Università della Campania Luigi Vanvitelli di Napoli- Dipartimento di epato-gastroenterologia; 🇮🇹 Napoli, Italy

UO di Gastroenterologia, Azienda ospedaliera di Padova; 🇮🇹 Padova, Italy

Medicina interna ed epatologia, Istituto clinico Humanitas; 🇮🇹 Rozzano, Italy

UO di Gastroenterologia e Endoscopia Digestiva, Ospedale Casa Sollievo della Sofferenza; 🇮🇹 San Giovanni Rotondo, Italy

Gastroenterologia ed endoscopia digestiva, Azienda provinciale per i servizi sanitari; 🇮🇹 Trento, Italy

SC (UCO) Clinica Patologie del Fegato, Ospedale di Cattinara, ASU GI; 🇮🇹 Trieste, Italy

Azienda Ospedaliera Universitaria Integrata Verona- UOC Gastroeneterologia A; 🇮🇹 Verona, Italy

Medicina clinica ed epatologia, Policlinico universitario campus bio-medico; 🇮🇹 Roma, Italy

UO di gastroenterologia ed endoscopia digestiva, Azienda macchi, Asst sette laghi; 🇮🇹 Varese, Italy