NAtural Course and Prognosis of PFIC and Effect of Biliary Diversion (NAPPED)

January 15, 2025 updated by: Prof. Dr. Henkjan J. Verkade, University Medical Center Groningen

NAtural Course and Prognosis of PFIC and Effect of Biliary Diversion (NAPPED Study), Meta-analysis of Individual Patient Data of PFIC Before and After Surgery (bile Diversion or Liver Transplantation)

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:

Define the natural course of disease in patients with genetically defined FIC1 deficiency (PFIC1), BSEP deficiency (PFIC2), MDR3 deficiency (PFIC3) and other subtypes of the PFIC disease family (including e.g. Myo5B deficiency, TJP2 deficiency, a.o.), 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 corresponding clinical phenotype .
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, follow up after surgical biliary diversion will be as long as possible.
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.
If patient numbers permit, to establish genotype-phenotype relationships for the most common genetic mutations causing the indicated diseases.

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.

Study Overview

Status

Enrolling by invitation

Conditions

Progressive Familial Intrahepatic Cholestasis

Intervention / Treatment

Procedure: Surgical biliary diversion

Study Type

Observational

Enrollment (Estimated)

1500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Netherlands
- - Groningen, Netherlands
    - University Medical Center Groningen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Sampling Method

Probability Sample

Study Population

The diagnosis of PFIC needs to be performed according to the international guidelines, based on (episodes with) the clinical symtpoms and identification of disease-causing mutations in the respective genes.

Description

Inclusion Criteria:

Clinical suspicion for FIC1-, BSEP- or MDR3-deficiency or of any other subtype of the PFIC family

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: Cohort
Time Perspectives: Retrospective

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
FIC1 deficiency (PFIC1), BSEP deficiency (PFIC2), MDR3 deficiency (PFIC3) and other PFIC subtypes	Procedure: Surgical biliary diversion Surgical interruption of enterohepatic circulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with liver transplantation Time Frame: at 18 years of age, as well as >18 years of age (until 65 years of age)	Underwent liver transplant	at 18 years of age, as well as >18 years of age (until 65 years of age)
Number of participants that succumbed Time Frame: at 18 years of age, as well as >18 years of age (until 65 years of age)	Succumbed	at 18 years of age, as well as >18 years of age (until 65 years of age)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participant undergoing a surgical biliary diversion Time Frame: at 5, 10, 15 and 18 years of age, as well as >18 years of age (until 65 years of age)	Underwent surgical biliary diversion	at 5, 10, 15 and 18 years of age, as well as >18 years of age (until 65 years of age)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 26, 2017

Primary Completion (Estimated)

January 1, 2032

Study Completion (Estimated)

January 1, 2032

Study Registration Dates

First Submitted

April 19, 2019

First Submitted That Met QC Criteria

April 26, 2019

First Posted (Actual)

April 29, 2019

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 15, 2025

Last Verified

December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

METc2017.106

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

product manufactured in and exported from the U.S.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

NAtural Course and Prognosis of PFIC and Effect of Biliary Diversion (NAPPED)