National Database on Primary Biliary Cholangitis

Primary Biliary Cholangitis Clinical Trial

— PBC322  

Official title:

Multicenter, Nationwide, Observational, Retrospective and Prospective Study Based on the Development of a Patients Database Linked to a Biological Sample Storage

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05151809
• Other study ID #: PBC322
• Status: Recruiting
• Start date: September 19, 2019
• Est. completion date: January 24, 2029

Study information

• Verified date: March 2023
• Source: University of Milano Bicocca
• Contact: Pietro Invernizzi, MD
• Phone: +39 039 233 2187
• Email: pietro.invernizzi[@]unimib.it
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6000
• Est. completion date: January 24, 2029
• Est. primary completion date: January 24, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cholangitis
• Liver Cirrhosis, Biliary
• Primary Biliary Cholangitis

Intervention

Other:
• Clinical information
The investigators will recruit PBC patients and collect important clinical information and laboratory investigation, together with biological samples.

Locations

Country	Name	City	State
Italy	Ospedali riuniti di Ancona	Ancona
Italy	A.O.U. Consorziale - Policlinico Bari- UO Gastroenterologia	Bari
Italy	UO di gastroenterologia, Asst Papa Giovanni XXIII	Bergamo
Italy	Policlinico S. Orsola Malpighi- UO Medicina Interna	Bologna
Italy	Policlinico S.Orsola Malpighi- Ambulatorio di epatologia e gestione trapianto epatico	Bologna
Italy	Gastroenterologia, fisiopatologia e endoscopia digestiva, Azienda sanitaria dell'alto adige	Bolzano
Italy	Unità epatologica ed ecografia internistica a valenza dipartimentale, Fondazione Ospedaliera Poliambulanza	Brescia
Italy	UO di gastroenterologia, Spedali civili di Brescia	Brescia
Italy	UO epatologia, Azienda ospedaliero università di Cagliari Policlinico universitario Monserrato	Cagliari
Italy	Ospedale IRCCS Saverio De Bellis- UOC di Gastroenterologia 1	Castellana Grotte
Italy	UO epatologia Ospedale Garibaldi	Catania
Italy	UO di fisiopatologia digestiva, Azienda Ospedaliera Universitaria Mater Domini	Catanzaro
Italy	UO di gastroenterologia, Ospedale Valduce	Como
Italy	Azienda Socio Sanitaria Territoriale (ASST) di Cremona- UO Medicina Interna - Ambulatori di Epatologia	Cremona
Italy	Presidio Ospedaliero di Faenza- UO Medicina Interna	Faenza
Italy	UO Clinica Medica, Azienda Ospedaliera Universitaria Careggi Firenze	Firenze
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 Clinica Gastroenterologica, Policlinico San Martino	Genova
Italy	Centro Medicina del Viaggiatore e delle Migrazioni, ASP Catanzaro, Presìdio Ospedaliero "Giovanni Paolo II"	Lamezia Terme
Italy	UO di epatologia clinica e biomolecolare, Università degli studi di Messina	Messina
Italy	University of Milano-Bicocca	Milan
Italy	Policlinico di Milano	Milano
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	AOU di Modena- U.O. Gastroenterologia	Modena
Italy	Struttura Complessa di Medicina ad Indirizzo Metabolico Nutrizionale, Dipartimento Ospedaliero di Medicina Interna	Modena
Italy	Day Hospital e Ambulatorio di Epatoogia e Nutrizione Clinica, Fondazione Evangelica Villa Betania, Ospedale generale di Zona	Napoli
Italy	Ospedale policlinico Federico II di Napoli	Napoli
Italy	Università della Campania Luigi Vanvitelli di Napoli- Dipartimento di epato-gastroenterologia	Napoli
Italy	UO medicina ed epatologia, Ospedale maggiore della carità	Novara
Italy	UO di Gastroenterologia, Azienda ospedaliera di Padova	Padova
Italy	UO di Medicina Interna, Azienda Ospedaliera di Padova	Padova
Italy	UO gastroenterologia, Policlinico Paolo Giaccone	Palermo
Italy	Malattie infettive ed epatologia, Azienda ospedaliero universitaria di Parma	Parma
Italy	Day Hospital Internistico e ambulatorio di Epatologia, ASL Pescara	Pescara
Italy	UO epatologia, AOU pisana Cisanello	Pisa
Italy	S.C. Gastroenterologia, Ospedale di Pordenone, AS FO	Pordenone
Italy	Medicina clinica ed epatologia, Policlinico universitario campus bio-medico	Roma
Italy	Policlinico Universitario Fondazione Agostino Gemelli- UO di medicina interna	Roma
Italy	UO di Epatologia, Universita' di Roma Tor Vergata	Roma
Italy	UO di Gastroenterologia, Policlinico Umberto I	Roma
Italy	Medicina interna ed epatologia, Istituto clinico Humanitas	Rozzano
Italy	Università degli studi di Salerno	Salerno
Italy	SSD Epatologia, Fondazione Casa Sollievo della Sofferenza	San Giovanni Rotondo
Italy	UO di Gastroenterologia e Endoscopia Digestiva, Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo
Italy	Azienda Ospedale Universitaria di Sassari- UOC Medicina Interna	Sassari
Italy	S.C. Gastroenterologia, Azienda Ospedaliero-Universitaria Molinette	Torino
Italy	Gastroenterologia ed endoscopia digestiva, Azienda provinciale per i servizi sanitari	Trento
Italy	Ospedale regionale Ca' Foncello di Treviso- Unità operativa complessa di Gastroenterologia	Treviso
Italy	SC (UCO) Clinica Patologie del Fegato, Ospedale di Cattinara, ASU GI	Trieste
Italy	SOS di DPT Epatologia e Trapianti di Fegato, ASU FC	Udine
Italy	UO di gastroenterologia ed endoscopia digestiva, Azienda macchi, Asst sette laghi	Varese
Italy	Azienda Ospedaliera Universitaria Integrata Verona- UOC Gastroeneterologia A	Verona

Sponsors (1)

Lead Sponsor	Collaborator
University of Milano Bicocca

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phenotypes and sub-phenotypes of PBC Italian patients	Identify and define distinct phenotypes and sub-phenotypes of PBC patients at higher risk of disease progression.	Overall duration of the study (10 years)
Secondary	Response to UDCA therapy	Defined as Alkaline Phosphatase Level<1 x upper limit of normal. The investigators will fit a multivariate analysis using logistic regression using baseline variables.	Overall duration of the study (10 years)
Secondary	Identification of factors influencing the progression of PBC	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.	Overall duration of the study (10 years)
Secondary	Safety and long-term efficacy of novel therapies	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.	Overall duration of the study (10 years)