Autologous BMNC Infusion for Liver Cirrhosis in Children With BA

Phase 1

Completed

• Conditions: Biliary Atresia
• Interventions: Combination Product: Autologous BMMC transplantation

• Registration Number: NCT05517317
• Lead Sponsor: Vinmec Research Institute of Stem Cell and Gene Technology

Brief Summary

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.

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 Timeline

• Study Start: 2015-01-01
• Primary Completion: 2022-05-30
• Study Completion: 2022-05-30
• Status Verified: 2022-08
• Study First Submitted: 2022-08-22
• Study First Submitted QC: 2022-08-23
• Last Update Submitted: 2022-08-23
• Study First Posted: 2022-08-26
• Last Update Posted: 2022-08-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Autologous BMMC infusion	Autologous BMMC transplantation	One administration of autologous bone marrow mononuclear cells via the hepatic artery

Primary Outcome Measures

Name	Time	Method
Adverse events and serious adverse events	up to the 12-month period following treatment	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

Secondary Outcome Measures

Name	Time	Method
The changes in cholestasis	up to the 12-month period following treatment	Using Total Bilirubin (units: mg/dL) to measure the changes in cholestasis
The changes in Liver function using Gamma GT	up to the 12-month period following treatment	Using GGT (Gamma GT) (units: U/L) to measure the changes in liver function.
The changes in Liver function using Aspart transaminase	up to the 12-month period following treatment	Using AST (Aspart transaminase) (units: U/L) to measure the changes in liver function.
The changes in Liver function using Alanine transaminase	up to the 12-month period following treatment	Using ALT (Alanine transaminase) (units: U/L) to measure the changes in liver function.
The changes in level of cirrhosis	up to the 12-month period following treatment	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
The changes in liver biopsy	up to the 12-month period following treatment	Liver biopsy is a powerful clinical tool to evaluate the changes in the level of cirrhosis.

Trial Locations

Locations (1)

Vinmec Research Institute of Stem Cell and Gene Technology; 🇻🇳 Hanoi, Vietnam