Autologous Endothelial Progenitor Cell Therapy for Reversal of Liver Cirrhosis

National University Health System (NUHS)

Status and phase: Unknown; Phase 3

Conditions: End Stage Liver Disease

Treatments: Drug: GCSF; Procedure: CD133 Cells Transplantation

Study type: Interventional

Funder types: Other

Identifiers

NCT03109236

2016/00711

Details and patient eligibility

About

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.

Full 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.

Enrollment: 66 estimated patients

Sex: All

Ages: 21 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

66 participants in 2 patient groups

Treatment

Experimental group

Description:

Patient will undergo CD133+ cells transplantation at stable compensated state. 5 dose GCSF will be administered 5 days consecutively before bone marrow harvesting. Approximately 250ml of bone marrow will be harvested and subjected to CD133 isolation using clinimacs (Miltenyi Biotec) in a closed system. Under ultrasound guidance, 50 mls of 50-100 million CD133 cells will be infused directly through transhepatic route into portal venous circulation of the liver over 5 mins.

Treatment:

Procedure: CD133 Cells Transplantation

Drug: GCSF

Control

Active Comparator group

Description:

Non-Transplant Arm: Patients will receive 5 doses of GCSF

Treatment:

Drug: GCSF