Clinical trial NCT04522869: Umbilical Cord Derived Mesenchymal Stem Cell (UC -MSC) Transplantation for Children Suffering From Biliary Atresia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Primary Biliary Cirrhosis
Keywords: liver cirrhosis
biliary atresia
Kasai's operation
Lead sponsor: Vinmec Research Institute of Stem Cell and Gene Technology
Sponsor class: OTHER
Collaborators: name: Number 2 Children's Hospital, Ho Chi Minh City
First posted: 2020-08-21
Enrollment: 20
Sex: ALL
Minimum age (years): 5
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The change of PELD scores during study
timeFrame: baseline, 3 months, 6 months, 9 months, 12 months
measure: The change of albumin (Liver function)
timeFrame: up to the 12-month period following treatment
measure: The change of total bilirubin (Liver function)
timeFrame: up to the 12-month period following treatment
measure: The change of prothrombin time
timeFrame: up to the 12-month period following treatment
measure: The change of liver biopsy
timeFrame: up to the 12-month period following treatment
Secondary outcomes:
measure: The number of Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: baseline, 3 months, 6 months, 9 months, 12 months (time frame: up to the 12-month period following treatment)
Other outcomes:
Locations:
city: Hà Nội
country: Vietnam
facility: Vinmec International Hospital Times City
state: Hanoi
city: Hanoi
country: Vietnam
facility: Vinmec Research Institute of Stem cell and Gene Technology
Study officials:
affiliation: Vinmec Research Institute of Stem Cell and Gene Technology
name: Liem Nguyen
role: PRINCIPAL_INVESTIGATOR
References: