Umbilical Cord-derived Mesenchymal Stem Cell Infusion in the Management of Adult Liver Cirrhosis

A Phase I, Open-label Trial on the Safety and Efficacy of Human Umbilical Cord-derived Mesenchymal Stem Cell Administration in the Management of Adult Liver Cirrhosis

This is a phase I, open label, single arm trial using UC-MSCs to treat patients with liver cirrhosis that includes 20 patients. The primary outcome measure will be change in MELD score at 3, 6, and 12 months after UC-MSC transplantation from baseline. The safety is assessed by frequency and severity of the adverse event or serious adverse event associated with stem cell injection. This study could reconfirm the efficacy of stem cell transplantation for liver cirrhosis and would open a novel cell therapy for the treatment of adult liver cirrhosis.

Study Overview

• Status: Recruiting
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Biological: Human umbilical cord-derived mesenchymal stem cell infusion

Detailed Description

Liver cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands and causes by many forms of liver diseases and conditions such as hepatitis and chronic alcoholism. Liver cirrhosis has become one of the major causes of morbidity and mortality with over one million people died due to cirrhosis in 2010 worldwide. Currently, the only curative treatment for end-stage liver disease is liver transplantation. However, the shortage in donor organ availability and the side-effect associated with long-term immunosuppression after transplant requires the development of new alternative therapies for liver cirrhosis. Recent clinical trials demonstrate that bone marrow-derived stem cells (BMDSCs) as well as umbilical cord-derive mesenchymal stem cells (UC-MSCs) improve liver function in patients with liver cirrhosis. In Vietnam, however, there are no clinical trials to date that investigate the potential of UC-MSCs for liver cirrhosis management. This is a phase I, open label, single arm trial using UC-MSCs to treat patients with liver cirrhosis that includes 20 patients. The primary outcome measure will be change in MELD score at 3, 6, and 12 months after UC-MSC transplantation from baseline. The safety is assessed by frequency and severity of the adverse event or serious adverse event associated with stem cell injection. This study could reconfirm the efficacy of stem cell transplantation for liver cirrhosis and would open a novel cell therapy for the treatment of adult liver cirrhosis

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Vietnam
  • Hanoi, Vietnam, 100000
    • Recruiting
    • Vinmec Research Institute of Stem Cell and Gene Technology
    • Contact: Nguyen T Liem, Prof; Phone Number: +84914740683; Email: v.phuongnh9@vinmec.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 to 70 years old.
• Patients diagnosed of liver cirrhosis: splenomegaly, elevated hepatic enzymes and/or esophageal varices detected by endoscopy, or liver biopsy demonstrated liver cirrhosis
• Be willing to complete the study and sign the consent form.

Exclusion Criteria:

• Younger than 18 or older than 70 years old
• Recent infection
• Patients with history of chronic diseases such as cancer, chronic hepatitis, chronic kidney disease.
• Any clinically significant blood coagulation disorder(s)

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: human umbilical cord-derived mesenchymal stem cell transplantation for patients with liver cirrhosis; Umbilical cords from healthy donor are processed with 24 hours after vaginal delivery. The cords are delivered in a sterilized jar the laboratory to process. After washing in PBS to remove any contaminating blood, the cord is cut into small pieces. The pieces are minced and digested by enzyme. The UC-MSCs is cultured and expanded using commercially available serum-free and xeno-free medium at 37°C in a humidified atmosphere with 5% CO2. The UC-MSCs is suspended in 15 ml of saline buffer

Biological: Human umbilical cord-derived mesenchymal stem cell infusion; Human umbilical cord-derived mesenchymal stem cell infusion in the management of adult liver cirrhosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse events and serious adverse events (AEs or SAEs)	To assess safety: the number of AEs or SAEs during and after allogenic umbilical cord-mesenchymal stem cells (UC-MSCs) infusion	up to the 12-month period following the first UC-MSCs infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of liver function through the Model for End Stage Liver Disease (MELD) score	The MELD score is negatively correlated with the liver function, in which higher scores indicative a poorer liver function. The MELD score decrease show clinical improvement. The MELD score is calculated using the following formula: MELD score = 10 * (0.957 ln (serum creatinine, mg/dl) + 0.378 ln (bilirubin, mg/dl) +1.12 ln (INR) + 0.643).	3 months, 6 months, 12 months after the UC-MSCs infusion
Change in health-related quality of life using Chronic Liver Disease Questionnaire - (CLDQ)	CLDQ was developed to evaluate the impact of chronic liver diseases (CLD) on quality of life. The CLDQ includes 29 items in the following domains: abdominal symptoms, fatigue, systemic symptoms, activity, emotional function and worry. The scores range from 1 to 7, whit higher values indicating better quality of life.	3 months, 6 months, 12 months after the UC-MSCs infusion

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: April 6, 2022
• First Submitted That Met QC Criteria: April 14, 2022
• First Posted (Actual): April 18, 2022

Study Record Updates

• Last Update Posted (Actual): April 18, 2022
• Last Update Submitted That Met QC Criteria: April 14, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: ISC.19.29

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