Autologous BMNC Infusion for Liver Cirrhosis in Children With BA

Biliary Atresia Clinical Trial

— ABMNCBA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05517317
• Other study ID #: ISC_22_88
• Status: Completed
• Phase: Phase 1
• Start date: January 1, 2015
• Est. completion date: May 30, 2022

Study information

• Verified date: August 2022
• Source: Vinmec Research Institute of Stem Cell and Gene Technology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 30, 2022
• Est. primary completion date: May 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months to 15 Years

Eligibility

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

Related Conditions & MeSH terms

• Biliary Atresia
• Liver Cirrhosis

Intervention

Combination Product:
• Autologous BMMC transplantation
One administration of autologous bone marrow mononuclear cells via the hepatic artery

Locations

Country	Name	City	State
Vietnam	Vinmec Research Institute of Stem Cell and Gene Technology	Hanoi

Sponsors (1)

Lead Sponsor	Collaborator
Vinmec Research Institute of Stem Cell and Gene Technology

Country where clinical trial is conducted

Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The changes in cholestasis	Using Total Bilirubin (units: mg/dL) to measure the changes in cholestasis	up to the 12-month period following treatment
Secondary	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
Secondary	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
Secondary	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
Secondary	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 If PELD> 15: bad results	up to the 12-month period following treatment
Secondary	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