Biliary Atresia, Fibrosis, Liver, Stem Cell
Conditions
Keywords
biliary atresia, liver fibrosis, stem cell
Brief summary
Recently, mesenchymal stem cell (MSC) transplantation has emerged as a promising treatment for liver cirrhosis in adults. Additionally, bone marrow-derived stem cell transplantation has shown success in treating children with biliary atresia (BA). This study aims to evaluate the efficacy of Umbilical Cord-Derived Mesenchymal Stem Cell (UC-MSC) therapy in BA through a multicentric randomized controlled trial.
Detailed description
Biliary atresia (BA) is the most common cause of chronic cholestasis in neonates and accounts for at least 50% of pediatric liver transplants. The incidence of BA is estimated to range from 1:5000 to 1:19000 live births. If the operation is not performed, all patients will die due to complications of liver cirrhosis. Recently, mesenchymal stem cell (MSC) transplantation has been found to be a promising treatment for liver cirrhosis in adults. Stem cell transplantation derived from bone marrow has also been successfully applied to children with BA. The aim of this study is to demonstrate the efficacy of Umbilical Cord-Derived Mesenchymal Stem Cell (UC-MSC) therapy in BA by planning a multicentric randomized controlled trial.
Interventions
DRUGStem Cell
UC-MSC transplantation will be administered twice to each patient in the study group via the hepatic artery: the first transplantation will be performed post-surgery at the beginning, and the second one will be performed 6 months later, with a dose of 1 million UC-MSC/kg.
OTHERControl
In this group, UC-MSC will not be administered. This group serves as a passive control. The standard treatments that are routinely provided to these patients will continue to be administered.
Sponsors
Necmi Kadıoğlu Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
This study is designed as a multicentric randomized controlled trial (RCT). Patients will be randomly divided into two groups. Treatment Group: 30 Kasai-operated BA patients who will receive UC-MSC transplantation, and Control Group: 30 BA patients who will only undergo Kasai operation. UC-MSC transplantation will be administered twice to each patient in the study group via the hepatic artery: the first transplantation will be performed post-surgery at the beginning, and the second one will be performed 6 months later, with a dose of 1 million UC-MSC/kg.
Eligibility
Sex/Gender
ALL
Age
2 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
* Infants were diagnosed with liver cirrhosis due to biliary atresia following Kasai's operation. * The patients two months old or older and exhibited signs of cirrhosis after the procedure, including hepatomegaly, congestive splenomegaly, elevated liver enzymes, esophageal varices (confirmed by endoscopy), and cirrhosis (confirmed by liver biopsy).
Exclusion criteria
* Epilepsy * Neurological disorders * Coagulation disorders * Diabetes * Syndromic type biliary atresia * Allergies to anesthetic agents * Severe health conditions such as cancer or failure of the heart, lungs, liver, or kidneys, active infections, and severe psychiatric disorders.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 2 years | Adverse events will be assessed during the stem cell applications, as well as at 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years after the application. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ALT levels (Alanine transaminase) | 2 years | The levels of ALT will be closely monitored in both groups. The values for this parameter will be recorded and evaluated individually for each patient. |
| AST levels (Aspartate trasnaminase) | 2 years | The levels of AST will be closely monitored in both groups. The values for each parameter will be recorded and evaluated individually for each patient. |
| Direct bilirubin levels | 2 years | The levels of direct bilirubin will be closely monitored in both groups. The values for each parameter will be recorded and evaluated individually for each patient. |
| Total bilirubin levels | 2 years | The levels of total bilirubin will be closely monitored in both groups. The values for each parameter will be recorded and evaluated individually for each patient. |
| GGT levels (Gama glutamil transferase) | 2 years | The levels of GGT will be closely monitored in both groups. The values for each parameter will be recorded and evaluated individually for each patient. |
| Liver biopsy | 2 years | Liver biopsy is a crucial clinical tool for assessing the progression and severity of cirrhosis |
| Pediatric End-Stage Liver Disease (PELD) score | 2 years | 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 Albumin (Unit: g / dL), bilirubin (units: mg / dL) and INR (international normalized ratio). |
| Re-operation rate | 2 years | The patients who need further surgical intervention will be noted. |
| Liver transplantation | 2 years | Liver transplantation will be evaluated. The number of patients requiring a liver transplant, along with the timing of the need, will be recorded. |
| Albumin levels | 2 years | The levels of albumin will be closely monitored in both groups. The values for each parameter will be recorded and evaluated individually for each patient. |
| INR (international normalized ratio) | 2 years | The levels of INR (international normalized ratio) will be closely monitored in both groups. The values for each parameter will be recorded and evaluated individually for each patient. |
| Cholangitis | 2 years | The number of cholangitis for each cases will be closely monitored in both groups. The frequency of cholangitis experienced by each patient will be recorded and evaluated. |
| Level of cirrhosis | 2 years | Level of cirrhosis will be assesed with PELD score. 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 Albumin (Unit: g / dL), bilirubin (units: mg / dL) and INR (international normalized ratio). |
Countries
Turkey (Türkiye)
Contacts
Primary ContactMustafa Azizoglu, MD, PhD
Outcome results
None listed