Umbilical Cord Derived Mesenchymal Stem Cell (UC -MSC) Transplantation for Children Suffering From Biliary Atresia

Study Overview
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Brief Summary
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Biliary atresia (BA) is the most frequent cause of chronic cholestasis in neonates, accounting for at least 50% of pediatric liver transplantation. BA incidence is estimated to range from 1:5000 to 1:19000 live births. All patients will die due to complications of liver cirrhosis if the operation is not performed. Recently, mesenchymal stem cell (MSC) transplantation has been found as a promising therapy for liver cirrhosis in adults. Bone marrow-derived stem cell transplantation was also performed successfully for children with BA. Compared to MSC isolation from bone marrow, isolating MSCs from umbilical cord (UC) tissue is a less invasive procedure. Furthermore, UC-derived MSCs (UC-MSCs) have been demonstrated to be safe and effective for liver cirrhosis in adults and different pediatric diseases, including liver cirrhosis due to primary biliary cirrhosis. The investigators will compare the outcomes of 17 Kasai operated BA patients who receive UC-MSC transplantation to 17 BA patients who only undergo Kasai operation. Two transplantations of UC - MSCs will be performed via the hepatic artery: the first transplant will be performed at baseline, and the second one will be performed 6 months later with a dosage of 1 million MSCs per kg of body weight. The frequency and severity of the adverse events or serious adverse events associated with UC-MSC injection at 72 hours post-injection will be used to assess the safety. The efficacy of the therapy will be measured using Pediatric End-Stage Liver Disease (PELD) score, liver function, and liver biopsy. This study would open a novel cell therapy to improve outcomes of patients with BA.

Detailed Description
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The study protocol was approved by the Vinmec International Hospital Ethics Committee, and National Ethics Committees. The stem cell products are conducted in accordance with (GMP) requirements and Good Clinical Practice (GCP). All patients and primary caregivers will receive a written consent form, a cover letter and a clear explanation of the safety issues, potential risks and benefits, and the procedure involved. Moreover, patients will be provided the updated results related to disease and the study during conducting the study and will be fully funded by the project.

Official Title
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Evaluation Safety and Efficacy of Umbilical Cord Derived Mesenchymal Stem Cell (UC -MSC) Transplantation for Children Suffering From Liver Cirrhosis Due to Biliary Atresia: A Matched Control Prospective Study

Conditions
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Primary Biliary Cirrhosis

Intervention / Treatment
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* Biological: Umbilical Cord Derived Mesenchymal Stem Cell (UC -MSC) Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children diagnosed with liver cirrhosis due to biliary atresia after Kasai's operation From 5 months to 2 years old Weight ≥ 6 kg Patients with manifestation of cirrhosis on liver biopsy during Kasai's operation. Parents or primary caregivers signed the informed consent form. Exclusion Criteria: Under 6kg or over 2 years old Coagulation disorders Allergy to anesthetic agents Active infections

Ages Eligible for Study
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Minimum Age: 5 Months
Maximum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Matched Control Prospective Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Umbilical cord blood - derived mesenchymal stem cells<br>17 patients with BA underwent Kasai operation and then will received two doses of UC-MSCs at 1x106 cells/kg (body weight) administered via hepatic artery | Biological: Umbilical Cord Derived Mesenchymal Stem Cell (UC -MSC) Transplantation<br>* Umbilical Cord Derived Mesenchymal Stem Cell (UC -MSC) Transplantation for Children Suffering From Liver Cirrhosis Due to Biliary Atresia<br>|
| No Intervention: Control group<br>17 patients with BA will be conducted Kasai operation only | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of PELD scores during study | The PELD score is calculated using the following formula: PELD Score = 0.480 * ln (Bilirubin in mg/dL) + 1.857 * ln (INR) - 0.687 * ln (Albumin in g/dL) + 0.436 if the patient is <1 year old + 0.667 if there growth failure | baseline, 3 months, 6 months, 9 months, 12 months | 
| The change of albumin (Liver function) | Levels of albumin (g/dL) | up to the 12-month period following treatment | 
| The change of total bilirubin (Liver function) | Total bilirubin level (mg/dL) | up to the 12-month period following treatment | 
| The change of prothrombin time | Prothrombin time (second) | up to the 12-month period following treatment | 
| The change of liver biopsy | change of liver biopsy | up to the 12-month period following treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of Adverse Events (AE) and Serious Adverse Events (SAE) | Adverse Events (AE) and Serious Adverse Events (SAE) after MSC transplantation | baseline, 3 months, 6 months, 9 months, 12 months (time frame: up to the 12-month period following treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver cirrhosis, biliary atresia, Kasai's operation