Evaluation of the Use of Granulocyte Colony Stimulating Factor (GCSF) in Post Kasai Type 3 Biliary Atresia

Not Applicable

Recruiting

• Conditions: Granulocyte Colony-stimulating Factor; Biliary Atresia
• Interventions: Drug: Granulocyte Colony-Stimulating Factor

• Registration Number: NCT06708572
• Lead Sponsor: National Liver Institute, Egypt

Brief Summary

The aim of the study is to evaluate the use of Granulocyte Colony Stimulating Factor (GCSF) on the clinical and biochemical outcome of type 3 biliary atresia post kasai.

Detailed Description

Biliary atresia (BA) is a devastating disease manifest early in infancy characterized by bile duct injury and extrahepatic biliary obstruction, leading to cirrhosis in the majority of infants.

Although BA is a rare disease, occurring in \~1 in 5600 to 1 in 18,000 infants worldwide, it is considered the most common indication for liver transplantation in children.

However, despite a 50-60% rate of initial jaundice clearance, liver transplantation by 2 years of age is necessary for long term survival in many of the post-Kasai patients.

GCSF cytokine that stimulates neutrophil and hematopoietic stem cell (HSC) production and mobilization from the bone marrow, and has served as a complementary agent to bone marrow stem cell therapy for patients with congenital or acquired diseases of bone marrow suppression.

Granulocyte colony-stimulating factor (G-CSF) mobilizes CD34+(cluster of differentiation34) cells, these CD34+ cells increase hepatocyte growth factor inducing the proliferation of hepatic progenitor cells within 7 days.

In experimental liver diseases of toxin-induced or bile duct ligation-induced liver injury, GCSF-based stem cell therapy has the same effects as direct HSC transplantation on improving liver regeneration and suppressing the inflammatory and fibrotic responses to hepatic injury. The cellular and molecular mechanisms are unknown but are postulated to be derived from the many paracrine actions of GCSF.

Study Timeline

• Status Verified: 2024-10
• Study First Submitted: 2024-10-14
• Study First Submitted QC: 2024-11-25
• Study First Posted: 2024-11-27
• Study Start: 2024-12
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-11
• Primary Completion: 2026-10-30
• Study Completion: 2026-10-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Infants with initial diagnosis of biliary atresia with biliary atresia score > 23.927 will be allocated for Kasai porto-enterostomy with intra-operative cholangiogram reaching type 3 biliary atresia anatomy as a final diagnosis.

Exclusion Criteria

• Major cardiac, renal, pulmonary, neurological malformations or illnesses.
• Hemoglobinopathies, such as sickle cell anemia
• Active systemic infection.
• White blood cell count > 20,000 cells/mm3.
• Platelet count < 40,000 cells/mm3 or ≥ 800,000 cells/mm3.
• Purpura fulminans or unexplained vascular thrombotic conditions.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
biliary atresia with GCSF	Granulocyte Colony-Stimulating Factor	20 infants with the final diagnosis of biliary atresia type 3 (supported by the liver histology and intra-operative finding) for GCSF after Kasai operation will receive GCSF.

Primary Outcome Measures

Name	Time	Method
Proportion of subjects with serum TBi (total bilirubin) ≥ 2 mg/dL at 3 months.	baseline	Proportion of subjects with serum TBi (total bilirubin) ≥ 2 mg/dL at 3 months will be analyzed using generalized linear mixed effects model (GLMM) with a logistic link function for the covariates as fixed effects, with study sites as random effect to control for site variability in management practices and patient characteristics. The covariates are potential confounders for poor outcome, such as age at the time of Kasai, presence of ductal plate malformation, cholangitis and possibly CMV IgM(cytomegalovirus immune globulin M antibodies) positivity.

Secondary Outcome Measures

Name	Time	Method
Differences in the proportion of subjects with cholangitis at 6 months.	base line	Differences in the proportion of subjects with cholangitis at 6 months will be calculated using the generalized linear mixed effect model with logistic link function for the covariates described in the primary outcome, with study sites as random effect to control for site variability in management practices and patient characteristics.

Trial Locations

Locations (1)

National Liver Institute; 🇪🇬 Cairo, Menofia Governorate, Egypt