Autologous Endothelial Progenitor Cell Therapy for Reversal of Liver Cirrhosis

End Stage Liver Disease Clinical Trial

Official title:

Autologous Endothelial Progenitor Cell Therapy for Reversal of Liver Cirrhosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03109236
• Other study ID #: 2016/00711
• Status: Recruiting
• Phase: Phase 3
• Start date: August 24, 2017
• Est. completion date: December 31, 2023

Study information

• Verified date: January 2021
• Source: National University Hospital, Singapore
• Contact: Nur Halisah
• Phone: 66015193
• Email: mdcnhj[@]nus.edu.sg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This proposal translates a hypothesis driven basic research into clinical setting to determine the potential of using autologous CD133+ cells to reverse fibrosis and improve clinical outcome for patients with end stage cirrhosis. This has significant impact on the management of cirrhosis.

Description:

This is a 2 arm randomised study patients with decompensated liver cirrhosis involving minimum of 23 and maximum of 33 patients in each arm.

The investigators propose that transplantation of mobilized autologous CD133+ cells harvested from the bone marrow directly into the liver has the ability to replace and regenerate the damaged sinusoidal endothelium as well as normalize macrophage and Natural Killer (NK) cell function. The niche provided by the refenestrated endothelium can polarize the macrophage to antifibrotic phenotype as well as directly inactivate the activated myofibroblast, resulting in reversal of liver fibrosis and improvement in liver function. Transplantation of cells will be via intraportal route delivered by percutaneous cannulation of the portal vein system.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

Inclusion Criteria:

• Liver cirrhosis of any aetiology but where active disease is controlled

• Childs A/B/C with Child-Pugh score >= 5

And either one of the following:

1. MELD score 10-27

2. Clinically significant portal hypertension as evidenced by gastroesophageal varices or ascites

Exclusion Criteria:

• MELD score >27

• INR>2.5

• HIV

• History of hematological or hepatic malignancy within 5 years from consent

• Other underlying malignancy with <1 year survival

• Presence of systemic diseases that may impact survival within 1 year.

• Listed for liver transplant

Related Conditions & MeSH terms

• End Stage Liver Disease
• Liver Cirrhosis
• Liver Diseases

Intervention

Drug:
• GCSF
5 doses of GCSF injection will be injected under the skin on the abdomen to mobilize the bone marrow cells.

Procedure:
• CD133 Cells Transplantation
Endothelial progenitor cells are harvested by CD133+ MACS (magnetic activated cell sorting) sort selection of bone marrow and a minimum of 1x 10^6 and up to 50-100 x 10^6 cells are transplanted to one lobe of the liver via a percutaneous catheter inserted into the portal venous system by percutaneous transhepatic approach for engraftment.

Locations

Country	Name	City	State
Singapore	National University Hospital	Singapore

Sponsors (4)

Lead Sponsor	Collaborator
National University Hospital, Singapore	Changi General Hospital, Singapore General Hospital, Tan Tock Seng Hospital

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement of Fibrosis Staging (Ishak)	Improvement of Fibrosis Staging (Ishak) > 1 point	3 months
Primary	Improvement of liver fibrosis on MRE (magnetic resonance elastography)	Improvement of liver fibrosis on MRE (magnetic resonance elastography) > 2 point	6 months
Primary	Improvement of MELD (Model of End stage Liver Disease) score or Child Pugh State	Improvement of MELD (Model of End stage Liver Disease) score or Child Pugh State by at least 2 points	6 months
Primary	Improvement of quantitative fibrosis	Improvement of quantitative fibrosis on histology > 10%	1 year
Secondary	Overall Survival and Improvement	Overall Survival	1 year
Secondary	Overall Improvement in Liver Function Tests	Improvement in Liver Function Tests, especially Total Bilirubin, Albumin and Prothrombin Time	1 year
Secondary	Improvement of Hepatic Venous Pressure	Improvement of Hepatic Venous Pressure	3 months
Secondary	Incidence of clinical decompensation	Frequency of Incidence of clinical decompensation	1 year
Secondary	Overall Improvement of Patient Reported outcome	Improvement of Patient Reported outcome (quality of life Short Form Health Survey SF-36 for liver cirrhosis)	6 months
Secondary	Overall Improvement of MELD score	Rate of deterioration of MELD score (Kaplan Meier analysis)	1 year