NCT04531878

BSEP Function Rescue During Childhood Inhereditary Cholestatic Diseases

Jian-She Wang of Children's Hospital of Fudan University

• Status: Withdrawn
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Children's Hospital of Fudan University · Academic / Other
• Sex: All
• Age: 2 Months – 18 Years
• Healthy volunteers: Not accepted

Summary

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

Detailed 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.

Conditions

• Hereditary Diseases
• Cholestasis, Intrahepatic

Interventions

Type	Name	Description
DRUG	4-Phenylbutyrate	4-phenylbutyrate therapy will be started at a daily dose of 200 mg kg/d divided in 2 oral doses of sodium phenylbutyrate (AMMONAPS, Swedish Orphan Inter AB). In order to get the best effect, the dose will be increased up to a maximum of 500 mg kg/d.

Timeline

• Start date: 2023-02-08
• Primary completion: 2023-02-08
• Completion: 2023-02-08
• First posted: 2020-08-31
• Last updated: 2023-02-09