Stem Cell Applications in Biliary Atresia Patients

Umbilical Cord Derived Mesenchymal Stem Cell (UC-MSC) Transplantation in Infants With Biliary Atresia: A Prospective Randomized Controlled Trial

Recently, mesenchymal stem cell (MSC) transplantation has emerged as a promising treatment for liver cirrhosis in adults. Additionally, bone marrow-derived stem cell transplantation has shown success in treating children with biliary atresia (BA). This study aims to evaluate the efficacy of Umbilical Cord-Derived Mesenchymal Stem Cell (UC-MSC) therapy in BA through a multicentric randomized controlled trial.

Study Overview

• Status: Recruiting
• Conditions: Fibrosis, Liver; Biliary Atresia; Stem Cell
• Intervention / Treatment: Drug: Stem Cell; Other: Control

Detailed Description

Biliary atresia (BA) is the most common cause of chronic cholestasis in neonates and accounts for at least 50% of pediatric liver transplants. The incidence of BA is estimated to range from 1:5000 to 1:19000 live births. If the operation is not performed, all patients will die due to complications of liver cirrhosis. Recently, mesenchymal stem cell (MSC) transplantation has been found to be a promising treatment for liver cirrhosis in adults. Stem cell transplantation derived from bone marrow has also been successfully applied to children with BA. The aim of this study is to demonstrate the efficacy of Umbilical Cord-Derived Mesenchymal Stem Cell (UC-MSC) therapy in BA by planning a multicentric randomized controlled trial.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mustafa Azizoglu, MD, PhD; Phone Number: +905447448244; Email: mdmazizoglu@gmail.com

Study Locations

• Turkey
  • Istanbul, Turkey, 34340
    • Recruiting
    • Esenyurt State Hospital
    • Contact: Mustafa Azizoglu, MD, PhD; Phone Number: +905447448244; Email: mdmazizoglu@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants were diagnosed with liver cirrhosis due to biliary atresia following Kasai's operation.
• The patients two months old or older and exhibited signs of cirrhosis after the procedure, including hepatomegaly, congestive splenomegaly, elevated liver enzymes, esophageal varices (confirmed by endoscopy), and cirrhosis (confirmed by liver biopsy).

Exclusion Criteria:

• Epilepsy
• Neurological disorders
• Coagulation disorders
• Diabetes
• Syndromic type biliary atresia
• Allergies to anesthetic agents
• Severe health conditions such as cancer or failure of the heart, lungs, liver, or kidneys, active infections, and severe psychiatric disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stem Cell Application Group; In this group, UC-MSC transplantation will be administered twice to each patient in the study group via the hepatic artery: the first transplantation will be performed post-surgery at the beginning, and the second one will be performed 6 months later, with a dose of 1 million UC-MSC/kg. The applications will be applied after kasai portoenterostomy.	Drug: Stem Cell; UC-MSC transplantation will be administered twice to each patient in the study group via the hepatic artery: the first transplantation will be performed post-surgery at the beginning, and the second one will be performed 6 months later, with a dose of 1 million UC-MSC/kg.
Sham Comparator: Control; In this group, UC-MSC will not be administered. This group serves as a passive control. The standard treatments that are routinely provided to Biliary Atresia patients will continue to be administered.	Other: Control; In this group, UC-MSC will not be administered. This group serves as a passive control. The standard treatments that are routinely provided to these patients will continue to be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Adverse events will be assessed during the stem cell applications, as well as at 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years after the application.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cholestasis	The number of cholestasis for each cases will be closely monitored in both groups. The frequency of cholestasis experienced by each patient will be recorded and evaluated.	2 years
Pediatric End-Stage Liver Disease (PELD) score	Using PELD score (according to the suggestion of The Liver and Intestinal Organ Transplantation Committee in 2009). PELD is calculated based on three indicators: albumin (g / dL), bilirubin (units: mg / dL) and INR (international normalized ratio). Formula: PELD = 10 * (0.48 * ln(Serum Bilirubin) + 1.857 * ln(INR) - 0.687 * ln(Albumin) + (0.436 if patient is less than 1 year old) + (0.667 if patient has growth failure)). Evaluate the result: If PELD <10: good results If 10 <PELD <15: average results If PELD> 15: bad results Albumin (Unit: g / dL), bilirubin (units: mg / dL) and INR (international normalized ratio).	2 years
ALT levels (Alanine transaminase)	The levels of ALT will be closely monitored in both groups. The values for this parameter will be recorded and evaluated individually for each patient.	2 years
AST levels (Aspartate trasnaminase)	The levels of AST will be closely monitored in both groups. The values for each parameter will be recorded and evaluated individually for each patient.	2 years
Direct bilirubin levels	The levels of direct bilirubin will be closely monitored in both groups. The values for each parameter will be recorded and evaluated individually for each patient.	2 years
Total bilirubin levels	The levels of total bilirubin will be closely monitored in both groups. The values for each parameter will be recorded and evaluated individually for each patient.	2 years
GGT levels (Gama glutamil transferase)	The levels of GGT will be closely monitored in both groups. The values for each parameter will be recorded and evaluated individually for each patient.	2 years
Liver biopsy	Liver biopsy is a crucial clinical tool for assessing the progression and severity of cirrhosis	2 years
Level of cirrhosis	Level of cirrhosis will be assesed with PELD score. Using PELD score (according to the suggestion of The Liver and Intestinal Organ Transplantation Committee in 2009). PELD is calculated based on three indicators: albumin (g / dL), bilirubin (units: mg / dL) and INR (international normalized ratio). Formula: PELD = 10 * (0.48 * ln(Serum Bilirubin) + 1.857 * ln(INR) - 0.687 * ln(Albumin) + (0.436 if patient is less than 1 year old) + (0.667 if patient has growth failure)). Evaluate the result: If PELD <10: good results If 10 <PELD <15: average results If PELD> 15: bad results Albumin (Unit: g / dL), bilirubin (units: mg / dL) and INR (international normalized ratio).	2 years
Re-operation rate	The patients who need further surgical intervention will be noted.	2 years
Liver transplantation	Liver transplantation will be evaluated. The number of patients requiring a liver transplant, along with the timing of the need, will be recorded.	2 years
Albumin levels	The levels of albumin will be closely monitored in both groups. The values for each parameter will be recorded and evaluated individually for each patient.	2 years
INR (international normalized ratio)	The levels of INR (international normalized ratio) will be closely monitored in both groups. The values for each parameter will be recorded and evaluated individually for each patient.	2 years

Collaborators and Investigators

• Sponsor: Necmi Kadıoğlu Hospital
• Investigators: Principal Investigator: Mustafa Azizoglu, MD, PhD, Esenyurt State Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: August 17, 2024
• First Submitted That Met QC Criteria: August 19, 2024
• First Posted (Actual): August 21, 2024

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: stem cell; liver fibrosis; biliary atresia
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Congenital Abnormalities; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Digestive System Abnormalities; Fibrosis; Liver Cirrhosis; Biliary Atresia
• Other Study ID Numbers: Biliar Atresia Stem Cell

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No