BSEP Function Rescue During Childhood Inhereditary Cholestatic Diseases

Fudan University

Status and phase

Withdrawn

Phase 3

Phase 2

Conditions

Hereditary Diseases

Cholestasis, Intrahepatic

Treatments

Drug: 4-Phenylbutyrate

Study type

Interventional

Funder types

Other

Identifiers

NCT04531878

BSEP_FudanEK_001

Details and patient eligibility

About

The purpose of the study is to improve the prognosis of inhereditary cholestasis caused by ABCB11 gene mutations by using BSEP function rescue drugs

Full description

Bile acids function as detergents to aid digestion and as signaling molecules to regulate gene expression and metabolism. They are synthesized from cholesterol in the liver, secreted into bile and re -turned from chyme to liver in portal- vein blood 6-10 times per day (enterohepatic circulation. Enterohepatic circulation of bile acids involves more than 20 transporters among which bile salt export pump (BSEP), encoded by ABCB11 plays a key role. BSEP medi-ates the secretion of bile acids across the canalicular membrane of hepatocytes into bile to provide the osmotic pressure for bile flow. Mutations in ABCB11 can cause absence or dysfunction of BSEP leading to cholestasis. Bile acid accumulation in hepatocytes caused by BSEP dysfunction is associated with a range of liver dis-eases, ranging from transient neonatal cholestasis to fatal progressive familial intrahepatic cholestasis (PFIC), with jaundice, growth retardation, cirrhosis, liver failure and death. Our current indicates that more than 70% patents with ABCB11 mutations need liver-transplantation or dead during follow-up. In recent years, some targeted drugs including 4-phenylbutyrate(for patients with BSEP trafficking abnormal), ivacaftor(for patients with abnormal BSEP transport function), and gentamicin (for patients with none sense mutations) have emerged make it possible for individual targeted therapy possible.

Sex

All

Ages

2 months to 18 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

with signed informed consent form from the guardian, and the patient if applicable.
aged from 2 month to 18 years old.
with cholestatic disease caused by ABCB11 biallelic mutation.
Long-term residence in China.

Exclusion criteria

Currently receiving or previously received experimental drugs.
The child is already in the stage of liver failure, or in unstable state that are not suitable for drug treatment according to the researcher's judgment: serious complications such as bleeding tendency and skin rash.
accompany with other chronic liver disease (viral hepatitis B and C, autoimmune hepatitis, wilson disease, cystic fibrosis, primary biliary cirrhosis, biliary atresia, sclerosing cholangitis, bile acid synthesis defects, and infections, cholestasis caused by space-occupying and other reasons).
Suffered from congenital TORCHES infection, including toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, EB virus, syphilis, HIV, etc.
With any other major medical conditions that may affect drug absorption, metabolism, or excretion based on the researcher's judgment.
Known or suspected hypersensitivity to any experimental drugs or their indigents.
Patients with alcohol or drug dependence.
In receiving any investigational drugs or within 60 days before enrollment.