Colangioids to find genetic causes of atypical primary sclerosing cholangitis

Colangioids to Define the Genetic Factors Involved in Atypical Primary Sclerosing Cholangitis

This project will use lab-grown bile duct organoids (colangioids) to test which genetic changes are linked to atypical primary sclerosing cholangitis in adults with confirmed or suspected PSC or in available liver tissue.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 90 Years
• Sex: All
• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico (Academic / other)
• Locations: 1 site (Milan, MI)
• Trial ID: NCT06865924 on ClinicalTrials.gov

What this trial studies

Primary sclerosing cholangitis is a progressive bile-duct disease with no proven drug to halt progression, and this project uses colangioids and assembloids as in vitro models to explore genetic contributors. The study will collect samples from adults with confirmed atypical PSC, patients undergoing biopsy for suspected PSC, surgical liver resections, post-transplant biopsies, and cholecystectomies, and will include previously genotyped patients carrying ciliopathy-associated variants. Researchers will generate patient-derived colangioids/assembloids, perform genetic analyses, and test pharmacological responses in the lab to link specific variants to cellular behavior and drug sensitivity. Results are intended to identify genetic drivers and potential therapeutic targets to guide future personalized approaches.

Who should consider this trial

Good fit: Adults aged 18–90 with confirmed atypical PSC, patients suspected of PSC undergoing liver biopsy, individuals providing liver tissue from resections, transplant biopsies or cholecystectomy, and previously genotyped patients with relevant ciliopathy variants are eligible.

Not a fit: Patients with active chronic viral hepatitis (HBV or HCV) or those unable or unwilling to provide suitable liver or bile duct tissue are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this work could pinpoint genetic drivers of atypical PSC and enable personalized drug testing on patient-derived bile duct models to guide future treatments.

How similar studies have performed: Organoid and colangioid models have been successfully used in laboratory research to model bile duct disease and to test drug responses, so this approach builds on emerging but not yet clinically established methods.

Eligibility criteria

Inclusion Criteria:

* Between 18 and 90 years of age
* Of both sexes
* willingness to sign informed consent for the study; Additional criteria group 1
* Patients with a confirmed aPSC diagnosis Additional criteria group 2
* patients with suspected PSC liver biopsy candidates Additional criteria group 3
* Patients not affected by aPSC listed for the following procedures:
* Liver resection for hepatocellular or other hepatic lesions (including secondary effects from other cancers and benign focal lesions, which will result in healthy liver tissue);
* Post-transplant biopsies of healthy liver;
* cholecystectomies. Additional criteria group 4
* Patients previously genotyped in the study "Impact of complete exoma sequencing on clinical management of patient with non-alcoholic liver steatosis and cryptogenic liver disease project code RF-2016-02364358" results carrying gene variants associated with ciliopathies

Exclusion Criteria:

-Positive for chronic viral hepatitis (HCV-RNA and HBsAg).

Where this trial is running

Milan, MI

• Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico — Milan, Mi, Italy (Recruiting)

Study contacts

• Study coordinator: Luca Vittorio Carlo Valenti, Doctor

Conditions PSC