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

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

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.

Study Overview

• Status: Unknown
• Conditions: Primary Biliary Cirrhosis
• Intervention / Treatment: Biological: Umbilical Cord Derived Mesenchymal Stem Cell (UC -MSC) Transplantation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Phuong Nguyen; Phone Number: 1421 (+84) 243 975; Email: v.phuongnh9@vinmec.com

Study Locations

• Vietnam
  • Hanoi, Vietnam, 10000
    • Not yet recruiting
    • Vinmec Research Institute of Stem Cell and Gene Technology
    • Contact: Phuong Nguyen, MPH
  • Hanoi
    • Hà Nội, Hanoi, Vietnam, 100000
      • Recruiting
      • Vinmec International Hospital Times City
      • Contact: Anh Hai Nguyen, MD, PhD; Phone Number: (+84)968863668; Email: haianhnguyenbm@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Umbilical cord blood - derived mesenchymal stem cells; 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; Umbilical Cord Derived Mesenchymal Stem Cell (UC -MSC) Transplantation for Children Suffering From Liver Cirrhosis Due to Biliary Atresia
No Intervention: Control group; 17 patients with BA will be conducted Kasai operation only

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Vinmec Research Institute of Stem Cell and Gene Technology
• Collaborators: Number 2 Children's Hospital, Ho Chi Minh City
• Investigators: Principal Investigator: Liem Nguyen, Vinmec Research Institute of Stem Cell and Gene Technology

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2019
• Primary Completion (Anticipated): September 25, 2021
• Study Completion (Anticipated): October 25, 2021

Study Registration Dates

• First Submitted: September 4, 2019
• First Submitted That Met QC Criteria: August 18, 2020
• First Posted (Actual): August 21, 2020

Study Record Updates

• Last Update Posted (Actual): September 1, 2020
• Last Update Submitted That Met QC Criteria: August 28, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: liver cirrhosis; biliary atresia; Kasai's operation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Congenital Abnormalities; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Digestive System Abnormalities; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Biliary; Biliary Atresia
• Other Study ID Numbers: ISC.19.10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: When the study complete

Drug and device information, study documents

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