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

NCT04522869 | Completed Phase 1 DMC

• 1 other identifier: ISC.19.10
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Primary Biliary Cirrhosis

Keywords

liver cirrhosis; biliary atresia; Kasai's operation

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (1)

• The number of Adverse Events (AE) and Serious Adverse Events (SAE)

  baseline, 3 months, 6 months, 9 months, 12 months (time frame: up to the 12-month period following treatment)

Study Arms (2)

Umbilical cord blood - derived mesenchymal stem cells

EXPERIMENTAL

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

Control group

NO INTERVENTION

17 patients with BA will be conducted Kasai operation only

Interventions

Umbilical Cord Derived Mesenchymal Stem Cell (UC -MSC) Transplantation BIOLOGICAL

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

Umbilical cord blood - derived mesenchymal stem cells

Eligibility Criteria

• Age: 5 Months - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• Under 6kg or over 2 years old
• Coagulation disorders
• Allergy to anesthetic agents
• Active infections

Sponsors & Collaborators

• Vinmec Research Institute of Stem Cell and Gene Technology: lead
• Number 2 Children's Hospital, Ho Chi Minh City: collaborator

Study Sites (2)

Vinmec International Hospital Times City

Hanoi, Hanoi, 100000, Vietnam

Location

Vinmec Research Institute of Stem cell and Gene Technology

Hanoi, 10000, Vietnam

Location

Related Publications (1)

• Nguyen TL, Nguyen HP, Bui TH, Phan TKT, Ngo DM, Ha TTH, Tran TT, Luu NAT, Phan TK, Ho PD. Outcomes of Allogeneic Umbilical Cord Mesenchymal Stem Cell Infusion for Liver Cirrhosis Due to Biliary Atresia After Kasai Operation. J Pediatr Surg. 2025 Nov;60(11):162624. doi: 10.1016/j.jpedsurg.2025.162624. Epub 2025 Sep 2.

  PMID: 40907882 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis, Biliary; Liver Cirrhosis; Biliary Atresia

Interventions

Transplantation

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative

Study Officials

• Liem Nguyen

  Vinmec Research Institute of Stem Cell and Gene Technology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2019
• First Posted: August 21, 2020
• Study Start: August 10, 2019
• Primary Completion: September 25, 2021
• Study Completion: October 25, 2021
• Last Updated: June 6, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

VN (2)