Autologous BMNC Infusion for Liver Cirrhosis in Children With BA (ABMNCBA)

Autologous Bone Marrow Mononuclear Cell Infusion for Liver Cirrhosis in Children With Biliary Atresia

To evaluate the safety and early outcomes of autologous bone marrow mononuclear cell (BMMNC) infusion for liver cirrhosis due to biliary atresia (BA) after Kasai operation. An open-label clinical trial was performed from January 2015 to December 2021. 12 children with liver cirrhosis due to BA at the time of Kasai or after Kasai were included. Bone marrow was harvested through anterior iliac crest puncture under general anesthesia. Mononuclear cells (MNCs) were isolated by Ficoll gradient centrifugation and then infused into the hepatic artery.

Study Overview

• Status: Completed
• Conditions: Biliary Atresia
• Intervention / Treatment: Combination product: Autologous BMMC transplantation

Detailed Description

Biliary atresia (BA) is a progressive fibro-obliterative cholangiopathy and a fatal disease. Without surgery, children with BA rarely survive beyond three years of age. The reported prevalence of BA ranges from 1 in 9640 to 1 in 19,500 live births. In the past, most children with a "non-correctable" type of BA died without adequate treatment. Recently, stem cell administration has been applied in adults with liver cirrhosis and has shown promising outcomes. An open-label clinical trial was performed from January 2015 to December 2021. 12 children with liver cirrhosis due to BA at the time of Kasai or after Kasai were included. Bone marrow was harvested through anterior iliac crest puncture under general anesthesia. Mononuclear cells (MNCs) were isolated by Ficoll gradient centrifugation and then infused into the hepatic artery. Serum bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and prothrombin time were monitored at baseline, three months, six months and 12 months after the transplantation. Esophagoscopies and liver biopsies were performed in patients whose parents provided consent. This study aimed to evaluate both safety and hepatic function after BMMNC administration in these children.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Vietnam
  • Hanoi, Vietnam, 100000
    • Vinmec Research Institute of Stem Cell and Gene Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children were diagnosed with Liver Cirrhosis Due to biliary atresia after Kasai's operation
• Two months old or older
• Patients with a manifestation of cirrhosis after Kasai's operation: hepatomegaly, congestive splenomegaly, elevated liver enzymes, Esophageal Varices (based on Endoscopic Diagnosis), cirrhosis (based on liver biopsy)

Exclusion Criteria:

• Epilepsy
• Coagulation disorders
• Allergy to anesthetic agents
• Severe health conditions such as cancer, failure of heart, lung, liver or kidney
• Active infections
• Severe psychiatric disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous BMMC infusion; One administration of autologous bone marrow mononuclear cells via the hepatic artery	Combination product: Autologous BMMC transplantation; One administration of autologous bone marrow mononuclear cells via the hepatic artery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events and serious adverse events	To assess safety, the number of AEs or SAEs during stem cell administration (72 h) at 1 month, 3 months, 6 months, and 9 months after discharge will be evaluated	up to the 12-month period following treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes in cholestasis	Using Total Bilirubin (units: mg/dL) to measure the changes in cholestasis	up to the 12-month period following treatment
The changes in Liver function using Aspart transaminase	Using AST (Aspart transaminase) (units: U/L) to measure the changes in liver function.	up to the 12-month period following treatment
The changes in Liver function using Alanine transaminase	Using ALT (Alanine transaminase) (units: U/L) to measure the changes in liver function.	up to the 12-month period following treatment
The changes in Liver function using Gamma GT	Using GGT (Gamma GT) (units: U/L) to measure the changes in liver function.	up to the 12-month period following treatment
The changes in level of cirrhosis	Using PELD score (according to the suggestion of The Liver and Intestinal Organ Transplantation Committee in 2009). PELD is calculated based on three indicators: albumin (g/dL), bilirubin (units: mg/dL) and INR (international normalized ratio). Formula: PELD = 10 * (0.48 * ln(Serum Bilirubin) + 1.857 * ln(INR) - 0.687 * ln(Albumin) + (0.436 if patient is less than 1 year old) + (0.667 if patient has growth failure). Evaluate the result: If PELD <10: good results If 10 <PELD <15: average results If PELD> 15: bad results	up to the 12-month period following treatment
The changes in liver biopsy	Liver biopsy is a powerful clinical tool to evaluate the changes in the level of cirrhosis.	up to the 12-month period following treatment

Collaborators and Investigators

• Sponsor: Vinmec Research Institute of Stem Cell and Gene Technology
• Investigators: Principal Investigator: Liem Thanh Nguyen, PhD, Vinmec Research Institute of Stem Cell and Gene Technology

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): May 30, 2022
• Study Completion (Actual): May 30, 2022

Study Registration Dates

• First Submitted: August 22, 2022
• First Submitted That Met QC Criteria: August 23, 2022
• First Posted (Actual): August 26, 2022

Study Record Updates

• Last Update Posted (Actual): August 26, 2022
• Last Update Submitted That Met QC Criteria: August 23, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Congenital Abnormalities; Liver Diseases; Fibrosis; Biliary Tract Diseases; Bile Duct Diseases; Digestive System Abnormalities; Liver Cirrhosis; Biliary Atresia
• Other Study ID Numbers: ISC_22_88

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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