Prospective Analysis of the Treatment of Progressive Familial Intrahepatic Cholestasis (TreatFIC)

NCT06778174 | Recruiting

• 1 other identifier: UGroningen - PaNaMaID11162
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The project has the following general aims:

1. 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. 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. 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. 4.(Surrogate) biomarker response: Biochemical parameters will be longitudinally collected and associated with changes in treatments / course of disease.
5. 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.

Conditions

Progressive Familial Intrahepatic Cholestasis

Keywords

PFIC; ASBT; IBAT; biliary diversion; liver transplantation

Outcome Measures

Primary Outcomes (1)

• Number of participants with liver transplantation

  The number (percentage) of patients undergoing liver transplantation related to the age of the patient

  at 5, 10, 15 and 18 years of age, as well as >18 years of age

Secondary Outcomes (1)

• Number of participants that succumbed

  at 5, 10, 15 and 18 years of age, as well as >18 years of age

Other Outcomes (1)

• Number of participant undergoing a surgical biliary diversion

  at 5, 10, 15 and 18 years of age, as well as >18 years of age

Study Arms (4)

FIC1-deficiency

genetically proven deficiency of FIC1 (FIC1). Disease is also known as PFIC1.

Other: observational study

BSEP-deficiency

genetically proven deficiency of Bile Salt Export Pump (BSEP, ABCB11). Disease is also known as PFIC2.

Other: observational study

MDR3-deficiency

genetically proven deficiency of Multi Drug Resistance protein type 3 (MDR3, ABCB4). Disease is also known as PFIC3.

Other: observational study

Other genetic subtypes of Familiai Intrahepatic Cholestasis

TJP2 deficiency (TJP2), FXR deficiency (NR1H4), SLC51A deficiency (SLC51A), USP53 deficiency (USP53), KIF12 deficiency (KIF12), ZFYE19 deficiency (ZFYVE19), MYO5B deficiency (MYO5B), SEMA7A deficiency (SEMA7A), VPS33B deficiency, (VPS33B), PSKH1 deficiency (PSKH1)

Other: observational study

Interventions

observational study OTHER

The interventions are not determined by the study, which is purely observational on "real world data".

Also known as: natural history, surgical biliary diversion, liver transplantation, IBAT-inhibition

BSEP-deficiency; FIC1-deficiency; MDR3-deficiency; Other genetic subtypes of Familiai Intrahepatic Cholestasis

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• \- 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.

You may not qualify if:

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

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9700 RB, Netherlands

RECRUITING

Related Publications (5)

• 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.

  PMID: 34478903 BACKGROUND

• 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.

  PMID: 36687469 BACKGROUND

• 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.

  PMID: 33991701 BACKGROUND

• 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.

  PMID: 33666275 BACKGROUND

• 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.

  PMID: 32087350 BACKGROUND

MeSH Terms

Conditions

Cholestasis, progressive familial intrahepatic 1

Interventions

Observation; Liver Transplantation

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques; Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative; Organ Transplantation; Transplantation

Central Study Contacts

Henkjan J Verkade, MD, PhD, Professor

CONTACT

31-50-3614147; h.j.verkade@umcg.nl; pfic@bkk.umcg.nl

Willem S Lexmond, MD, PhD

CONTACT

31-50-3614147; w.s.lexmond@umcg.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric hepatologist, Professor of pediatrics

Study Record Dates

• First Submitted: January 10, 2025
• First Posted: January 16, 2025
• Study Start: February 9, 2023
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): December 1, 2033
• Last Updated: January 24, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)