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

NCT ID: NCT06778174

Last Updated: 2025-01-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-02-09

Study Completion Date

2033-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Progressive Familial Intrahepatic Cholestasis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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FIC1-deficiency

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

observational study

Intervention Type OTHER

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

BSEP-deficiency

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

observational study

Intervention Type OTHER

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

MDR3-deficiency

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

observational study

Intervention Type OTHER

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

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)

observational study

Intervention Type OTHER

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

Interventions

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observational study

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

Intervention Type OTHER

Other Intervention Names

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natural history surgical biliary diversion liver transplantation IBAT-inhibition

Eligibility Criteria

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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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Medical Center Groningen

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. Henkjan J. Verkade

Pediatric hepatologist, Professor of pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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University Medical Center Groningen

Groningen, , Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Henkjan J Verkade, MD, PhD, Professor

Role: CONTACT

Willem S Lexmond, MD, PhD

Role: CONTACT

31-50-3614147

Facility Contacts

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Henkjan J Verkade, MD, PhD, Professor

Role: primary

Willem S Lexmond, MD, PhD

Role: backup

31-50-3614147

References

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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.

Reference Type BACKGROUND
PMID: 34478903 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36687469 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33991701 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33666275 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32087350 (View on PubMed)

Other Identifiers

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UGroningen - PaNaMaID11162

Identifier Type: -

Identifier Source: org_study_id

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