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

Vinmec Research Institute of Stem Cell and Gene Technology

Status and phase: Completed; Phase 2; Phase 1

Conditions: Primary Biliary Cirrhosis

Treatments: Biological: Umbilical Cord Derived Mesenchymal Stem Cell (UC -MSC) Transplantation

Study type: Interventional

Funder types: Other

Identifiers

NCT04522869

ISC.19.10

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 5 months to 2 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Umbilical cord blood - derived mesenchymal stem cells

Experimental group

Description:

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

Treatment:

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

Control group

No Intervention group

Description:

17 patients with BA will be conducted Kasai operation only