NAtural Course and Prognosis of PFIC and Effect of Biliary Diversion

• Conditions: Progressive Familial Intrahepatic Cholestasis
• Interventions: Procedure: Surgical biliary diversion

• Registration Number: NCT03930810
• Lead Sponsor: University Medical Center Groningen

Brief Summary

The natural course of PFIC syndromes and the effect of diversion techniques, have so far not been characterized in a rigorous manner within a larger population of patients. In fact, the clinical or biochemical parameters which most directly define and/or predict the success of reduced enterohepatic circulation (either by surgical diversion or medically) are still unclear.

The present project aims to:

1. Define the natural course of disease in genetically defined PFIC1, and PFIC2 patients, with respect to relevant biochemical and clinical parameters (and if available, histological). Included will be patients homozygous for a known, disease-causing mutation, patients compound homozygous for two disease-causing mutations or heterozygous for one disease-causing mutation in combination with the clinical phenotype of Bsep-deficiency or FIC1-deficiency.

2. Define the change in the natural course of disease in response to biliary diversion surgery and or liver transplantation, based on short- and long(er)-term changes in biochemical (if available, histological) and clinical parameters, including outcome measures. Follow up after transplantation will be limited to max 3 months after transplant surgery, follow up after surgical biliary diversion will be as long as possible.

3. Assessment of biochemical variables as possible surrogate endpoints for clinical hard endpoints. If possible this allows for identification of low-risk to high-risk patients early during follow-up.

4. If patient numbers permit, to establish genotype-phenotype relationships for the most common genetic mutations causing Bsep-deficiency or FIC1-deficiency.

Based on this project it is anticipated that the investigators are able:

* to characterize the variation in natural course of disease (whether or not genotype dependent) to allow clinicians to rationally select a target population for assessing the effect of medical intervention, rather than surgical biliary diversion);

* to identify and qualify one or more biomarkers that independently predict either improved or poor clinical outcomes of surgical biliary diversion;

* to investigate if the identified biomarker(s) can be used as surrogate end point(s) for assessing and predicting outcomes with novel interventional strategies.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2017-01-26
• Study First Submitted: 2019-04-19
• Study First Submitted QC: 2019-04-26
• Study First Posted: 2019-04-29
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-09
• Last Update Posted: 2023-01-10
• Primary Completion: 2032-01-01
• Study Completion: 2032-01-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 582

Inclusion Criteria

• Clinical suspicion for Bsep- or FIC1-deficiency

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
FIC1-deficiency and Bsep-deficiency	Surgical biliary diversion	-

Primary Outcome Measures

Name	Time	Method
Number of participants with liver transplantation	at 18 years of age	Underwent liver transplant
Number of participants that succumbed	at 18 years of age	Succumbed

Secondary Outcome Measures

Name	Time	Method
Number of participant undergoing a surgical biliary diversion	at 5, 10, 15 and 18 years of age	Underwent surgical biliary diversion

Trial Locations

Locations (1)

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands