Clinical trial NCT06778174: Prospective Analysis of the Treatment of Progressive Familial Intrahepatic Cholestasis (TreatFIC)
Official title: Prospective Analysis of the Treatment of Progressive Familial Intrahepatic Cholestasis (TreatFIC)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Progressive Familial Intrahepatic Cholestasis
Keywords: PFIC
ASBT
IBAT
biliary diversion
liver transplantation
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2025-01-16
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The diagnosis of a PFIC type disease needs to be performed according to the international guidelines, based on (episodes with a) low gamma-GT cholestasis and identification of disease-causing mutations in the indicated genes.

Brief summary: The project has the following general aims:

1. Natural course and prognosis: To prospectively follow the natural course and prognosis of the different types of PFIC, to broaden the understanding of the different very rare diseases and to allow predictions about the course of disease in different types of PFIC.
2. Efficacy: To define the course of disease in FIC patients and identify associations with different treatments (symptomatic treatments, interruption of the enterohepatic circulation by surgical or medical means and other therapies such as corrector/potentiator or exon skipping therapy. The course of disease will be characterized by biochemical, clinical and surgical parameters, including liver transplantation.
3. Safety: To define the complications associated with the different treatments (symptomatic treatments, interruption of the enterohepatic circulation by surgical or medical means and other therapies such as corrector/potentiator or exon skipping therapy, liver transplantation). Follow up will be as long as possible.
4. (Surrogate) biomarker response: Biochemical parameters will be longitudinally collected and associated with changes in treatments / course of disease.
5. Genotype-phenotype relationships: If patient numbers permit, to establish genotype-phenotype relationships for (non)responsiveness towards different treatments in patients with genetic mutations causing the different forms of FIC disease.


Eligibility criteria: Inclusion Criteria:

- Genetically confirmed cases of a PFIC type disease: FIC1 deficiency, BSEP deficiency, MDR3 deficiency, TJP2 deficiency, FXR deficiency, SLC51A deficiency, USP53 deficiency, KIF12 deficiency, ZFYE19 deficiency, MYO5B deficiency, SEMA7A deficiency, VPS33B deficiency, PSKH1 deficiency.

Exclusion Criteria:

- Cases with suspected PFIC type disease, but without genetic testing data available.

Primary outcomes:
measure: Number of participants with liver transplantation
timeFrame: at 5, 10, 15 and 18 years of age, as well as >18 years of age
Secondary outcomes:
measure: Number of participants that succumbed
timeFrame: at 5, 10, 15 and 18 years of age, as well as >18 years of age
Other outcomes:
measure: Number of participant undergoing a surgical biliary diversion
timeFrame: at 5, 10, 15 and 18 years of age, as well as >18 years of age
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
References:
citation: Felzen A, Verkade HJ. The spectrum of Progressive Familial Intrahepatic Cholestasis diseases: Update on pathophysiology and emerging treatments. Eur J Med Genet. 2021 Nov;64(11):104317. doi: 10.1016/j.ejmg.2021.104317. Epub 2021 Aug 31.
citation: Felzen A, van Wessel DBE, Gonzales E, Thompson RJ, Jankowska I, Shneider BL, Sokal E, Grammatikopoulos T, Kadaristiana A, Jacquemin E, Spraul A, Lipinski P, Czubkowski P, Rock N, Shagrani M, Broering D, Nicastro E, Kelly D, Nebbia G, Arnell H, Fischler B, Hulscher JBF, Serranti D, Arikan C, Polat E, Debray D, Lacaille F, Goncalves C, Hierro L, Munoz Bartolo G, Mozer-Glassberg Y, Azaz A, Brecelj J, Dezsofi A, Calvo PL, Grabhorn E, Hartleif S, van der Woerd WJ, Kamath BM, Wang JS, Li L, Durmaz O, Kerkar N, Jorgensen MH, Fischer R, Jimenez-Rivera C, Alam S, Cananzi M, Laverdure N, Ferreira CT, Guerrero FO, Wang H, Sency V, Kim KM, Chen HL, de Carvalho E, Fabre A, Bernabeu JQ, Zellos A, Alonso EM, Sokol RJ, Suchy FJ, Loomes KM, McKiernan PJ, Rosenthal P, Turmelle Y, Horslen S, Schwarz K, Bezerra JA, Wang K, Hansen BE, Verkade HJ; NAtural course and Prognosis of PFIC and Effect of biliary Diversion (NAPPED) Consortium. Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency. JHEP Rep. 2022 Nov 16;5(2):100626. doi: 10.1016/j.jhepr.2022.100626. eCollection 2023 Feb.
citation: van Wessel DBE, Gonzales E, Hansen BE, Verkade HJ. Defining the natural history of rare genetic liver diseases: Lessons learned from the NAPPED initiative. Eur J Med Genet. 2021 Jul;64(7):104245. doi: 10.1016/j.ejmg.2021.104245. Epub 2021 May 13.
citation: van Wessel DBE, Thompson RJ, Gonzales E, Jankowska I, Shneider BL, Sokal E, Grammatikopoulos T, Kadaristiana A, Jacquemin E, Spraul A, Lipinski P, Czubkowski P, Rock N, Shagrani M, Broering D, Algoufi T, Mazhar N, Nicastro E, Kelly D, Nebbia G, Arnell H, Fischler B, Hulscher JBF, Serranti D, Arikan C, Debray D, Lacaille F, Goncalves C, Hierro L, Munoz Bartolo G, Mozer-Glassberg Y, Azaz A, Brecelj J, Dezsofi A, Luigi Calvo P, Krebs-Schmitt D, Hartleif S, van der Woerd WL, Wang JS, Li LT, Durmaz O, Kerkar N, Horby Jorgensen M, Fischer R, Jimenez-Rivera C, Alam S, Cananzi M, Laverdure N, Targa Ferreira C, Ordonez F, Wang H, Sency V, Mo Kim K, Chen HL, Carvalho E, Fabre A, Quintero Bernabeu J, Alonso EM, Sokol RJ, Suchy FJ, Loomes KM, McKiernan PJ, Rosenthal P, Turmelle Y, Rao GS, Horslen S, Kamath BM, Rogalidou M, Karnsakul WW, Hansen B, Verkade HJ; Natural Course and Prognosis of PFIC and Effect of Biliary Diversion Consortium. Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency. Hepatology. 2021 Aug;74(2):892-906. doi: 10.1002/hep.31787. Epub 2021 Jul 13.
citation: van Wessel DBE, Thompson RJ, Gonzales E, Jankowska I, Sokal E, Grammatikopoulos T, Kadaristiana A, Jacquemin E, Spraul A, Lipinski P, Czubkowski P, Rock N, Shagrani M, Broering D, Algoufi T, Mazhar N, Nicastro E, Kelly DA, Nebbia G, Arnell H, Bjorn Fischler, Hulscher JBF, Serranti D, Arikan C, Polat E, Debray D, Lacaille F, Goncalves C, Hierro L, Munoz Bartolo G, Mozer-Glassberg Y, Azaz A, Brecelj J, Dezsofi A, Calvo PL, Grabhorn E, Sturm E, van der Woerd WJ, Kamath BM, Wang JS, Li L, Durmaz O, Onal Z, Bunt TMG, Hansen BE, Verkade HJ; NAtural course and Prognosis of PFIC and Effect of biliary Diversion (NAPPED) consortium. Genotype correlates with the natural history of severe bile salt export pump deficiency. J Hepatol. 2020 Jul;73(1):84-93. doi: 10.1016/j.jhep.2020.02.007. Epub 2020 Feb 20.