Clinical trial NCT05151809: National Database on Primary Biliary Cholangitis
Official title: Multicenter, Nationwide, Observational, Retrospective and Prospective Study Based on the Development of a Patients Database Linked to a Biological Sample Storage
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Primary Biliary Cholangitis
Keywords: Primary Biliary Cholangitis
Disease phenotypes
National Database
Lead sponsor: University of Milano Bicocca
Sponsor class: OTHER
First posted: 2021-12-09
Enrollment: 6000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All the italian patients fulfilling the diagnostic criteria for Primary Biliary Cholangitis (European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009 Aug;51(2):237-67) and aged at least 18.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phenotypes and sub-phenotypes of PBC Italian patients
timeFrame: Overall duration of the study (10 years)
Secondary outcomes:
measure: Response to UDCA therapy
timeFrame: Overall duration of the study (10 years)
measure: Identification of factors influencing the progression of PBC
timeFrame: Overall duration of the study (10 years)
measure: Safety and long-term efficacy of novel therapies
timeFrame: Overall duration of the study (10 years)
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Ospedali riuniti di Ancona
city: Bari
country: Italy
facility: A.O.U. Consorziale - Policlinico Bari- UO Gastroenterologia
city: Bergamo
country: Italy
facility: UO di gastroenterologia, Asst Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Policlinico S. Orsola Malpighi- UO Medicina Interna
city: Bologna
country: Italy
facility: Policlinico S.Orsola Malpighi- Ambulatorio di epatologia e gestione trapianto epatico
city: Bolzano
country: Italy
facility: Gastroenterologia, fisiopatologia e endoscopia digestiva, Azienda sanitaria dell'alto adige
city: Brescia
country: Italy
facility: Unità epatologica ed ecografia internistica a valenza dipartimentale, Fondazione Ospedaliera Poliambulanza
city: Brescia
country: Italy
facility: UO di gastroenterologia, Spedali civili di Brescia
city: Cagliari
country: Italy
facility: UO epatologia, Azienda ospedaliero università di Cagliari Policlinico universitario Monserrato
city: Castellana Grotte
country: Italy
facility: Ospedale IRCCS Saverio De Bellis- UOC di Gastroenterologia 1
city: Catania
country: Italy
facility: UO epatologia Ospedale Garibaldi
city: Catanzaro
country: Italy
facility: UO di fisiopatologia digestiva, Azienda Ospedaliera Universitaria Mater Domini
city: Como
country: Italy
facility: UO di gastroenterologia, Ospedale Valduce
city: Cremona
country: Italy
facility: Azienda Socio Sanitaria Territoriale (ASST) di Cremona- UO Medicina Interna - Ambulatori di Epatologia
city: Faenza
country: Italy
facility: Presidio Ospedaliero di Faenza- UO Medicina Interna
city: Firenze
country: Italy
facility: UO Clinica Medica, Azienda Ospedaliera Universitaria Careggi Firenze
city: Foggia
country: Italy
facility: Centro C.U.R.E. Centro Universitario per la ricerca e la Cura delle Malattie Epatiche
city: Gallarate
country: Italy
facility: Ambulatorio di Malattie del Fegato, U.O. Medicina, ASST Valle Olona, Presidio di Gallarate
city: Genova
country: Italy
facility: UO Clinica Gastroenterologica, Policlinico San Martino
city: Lamezia Terme
country: Italy
facility: Centro Medicina del Viaggiatore e delle Migrazioni, ASP Catanzaro, Presìdio Ospedaliero "Giovanni Paolo II"
city: Messina
country: Italy
facility: UO di epatologia clinica e biomolecolare, Università degli studi di Messina
city: Milano
country: Italy
facility: Policlinico di Milano
city: Milano
country: Italy
facility: UO di epatologia, Ospedale Niguarda Ca' Granda
city: Milano
country: Italy
facility: UO di Epatologia, Ospedale San Giuseppe
city: Milano
country: Italy
facility: UO epatologia, Istituto scientifico universitario San Raffaele
city: Milan
country: Italy
facility: University of Milano-Bicocca
city: Modena
country: Italy
facility: AOU di Modena- U.O. Gastroenterologia
city: Modena
country: Italy
facility: Struttura Complessa di Medicina ad Indirizzo Metabolico Nutrizionale, Dipartimento Ospedaliero di Medicina Interna
city: Napoli
country: Italy
facility: Day Hospital e Ambulatorio di Epatoogia e Nutrizione Clinica, Fondazione Evangelica Villa Betania, Ospedale generale di Zona
city: Napoli
country: Italy
facility: Ospedale policlinico Federico II di Napoli
city: Napoli
country: Italy
facility: Università della Campania Luigi Vanvitelli di Napoli- Dipartimento di epato-gastroenterologia
city: Novara
country: Italy
facility: UO medicina ed epatologia, Ospedale maggiore della carità
city: Padova
country: Italy
facility: UO di Gastroenterologia, Azienda ospedaliera di Padova
city: Padova
country: Italy
facility: UO di Medicina Interna, Azienda Ospedaliera di Padova
city: Palermo
country: Italy
facility: UO gastroenterologia, Policlinico Paolo Giaccone
city: Parma
country: Italy
facility: Malattie infettive ed epatologia, Azienda ospedaliero universitaria di Parma
city: Pescara
country: Italy
facility: Day Hospital Internistico e ambulatorio di Epatologia, ASL Pescara
city: Pisa
country: Italy
facility: UO epatologia, AOU pisana Cisanello
city: Pordenone
country: Italy
facility: S.C. Gastroenterologia, Ospedale di Pordenone, AS FO
city: Roma
country: Italy
facility: Medicina clinica ed epatologia, Policlinico universitario campus bio-medico
city: Roma
country: Italy
facility: Policlinico Universitario Fondazione Agostino Gemelli- UO di medicina interna
city: Roma
country: Italy
facility: UO di Epatologia, Universita' di Roma Tor Vergata
city: Roma
country: Italy
facility: UO di Gastroenterologia, Policlinico Umberto I
city: Rozzano
country: Italy
facility: Medicina interna ed epatologia, Istituto clinico Humanitas
city: Salerno
country: Italy
facility: Università degli studi di Salerno
city: San Giovanni Rotondo
country: Italy
facility: SSD Epatologia, Fondazione Casa Sollievo della Sofferenza
city: San Giovanni Rotondo
country: Italy
facility: UO di Gastroenterologia e Endoscopia Digestiva, Ospedale Casa Sollievo della Sofferenza
city: Sassari
country: Italy
facility: Azienda Ospedale Universitaria di Sassari- UOC Medicina Interna
city: Torino
country: Italy
facility: S.C. Gastroenterologia, Azienda Ospedaliero-Universitaria Molinette
city: Trento
country: Italy
facility: Gastroenterologia ed endoscopia digestiva, Azienda provinciale per i servizi sanitari
city: Treviso
country: Italy
facility: Ospedale regionale Ca' Foncello di Treviso- Unità operativa complessa di Gastroenterologia
city: Trieste
country: Italy
facility: SC (UCO) Clinica Patologie del Fegato, Ospedale di Cattinara, ASU GI
city: Udine
country: Italy
facility: SOS di DPT Epatologia e Trapianti di Fegato, ASU FC
city: Varese
country: Italy
facility: UO di gastroenterologia ed endoscopia digestiva, Azienda macchi, Asst sette laghi
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona- UOC Gastroeneterologia A
Study officials:
References: