NCT06856252: REASON

Human Liver ORganoids as a Model to Study the Development of Non-Alcoholic SteatOhepatitis (NASH)

Recruiting now NA Last updated 20 November 2025

What this trial tests

NA trial testing Liver resection to isolate cells in NAFLD in 60 participants. Currently enrolling.

Timeline

1 July 2021

Primary endpoint
31 July 2030

31 July 2032

Quick facts

Lead sponsor	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Phase	NA
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	prevention
Enrollment	60
Start date	1 July 2021
Primary completion	31 July 2030
Estimated completion	31 July 2032
Sites	1 location across Italy

Drugs / interventions tested

• Liver resection to isolate cells

Conditions studied

• NAFLD — all drugs for NAFLD →

Sponsor

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Who can join

18 and older, any sex, with NAFLD. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The primary objective of the study is to generate and characterize three-dimensional models, called "assembloids", composed of the main liver cell populations (in particular from the co-culture of organoids with stellate cells, responsible for fibrogenesis, deriving from clinical samples). These models will be used in order to imitate the first phases of the onset of steatohepatitis, in conditions of altered lipid metabolism (induced through exposure to the main environmental determinants of this condition: excess fatty acids, fructose, cholesterol) in the presence or absence of the mutation I148M of PNPLA3. Other genetic variants will also be analyzed, such as TM6SF2, MBOAT7 and GCKR, which have previously been correlated with the development of non-alcoholic steatohepatitis.

Further objectives will be: 1) identify new biomarkers of pathological activation of human stellate cells and progression of liver damage, to be subsequently validated in clinical case series for future use in clinical management for individual risk stratification; 2) study the epigenetic factors that underlie the onset of non-alcoholic steatohepatitis and its progression to fibrosis, cirrhosis and HCC; 3) evaluate the impact of antisense oligonucleotides directed against PNPLA3 on the severity of the "steatohepatitic" phenotype (lipid accumulation, lipotoxicity and inflammation and fibrogenesis) in assembloids

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Mastering Organoid Growth: A Complete Guide to Overcoming Methodological Challenges.
   Jiao C, Karakaya OF, Dadgar N, Wehrle CJ, et al · · 2026 · PMID 41503024 · DOI 10.1002/mco2.70571
2. Application of stem cells in the precise diagnosis and treatment of liver diseases.
   Wang YX, Ren YN, Zhang SS, Sun S, et al · · 2025 · PMID 41479645 · DOI 10.3748/wjg.v31.i46.114415