Clinical trial NCT03109236: Autologous Endothelial Progenitor Cell Therapy for Reversal of Liver Cirrhosis
Official title: Autologous Endothelial Progenitor Cell Therapy for Reversal of Liver Cirrhosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: End Stage Liver Disease
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
Collaborators: name: Singapore General Hospital
name: Tan Tock Seng Hospital
name: Changi General Hospital
First posted: 2017-04-12
Enrollment: 66
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a 2 arm randomised study patients with decompensated liver cirrhosis involving 33 patients in each arm. Randomisation will be done by statistician to determine which arm patients will be in (control / treatment).

Treatment arm:

Patient will undergo CD133+ cells transplantation at stable compensated state. 5 dose Granulocyte Colony Stimulating Factor (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.

Control Arm:

Patients will receive 5 doses of GCSF
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Improvement of Fibrosis Staging (Ishak)
timeFrame: 3 months
measure: Improvement of liver fibrosis on MRE (magnetic resonance elastography)
timeFrame: 6 months
measure: Improvement of MELD (Model of End stage Liver Disease) score or Child Pugh State
timeFrame: 6 months
measure: Improvement of quantitative fibrosis
timeFrame: 1 year
Secondary outcomes:
measure: Overall Survival and Improvement
timeFrame: 1 year
measure: Overall Improvement in Liver Function Tests
timeFrame: 1 year
measure: Improvement of Hepatic Venous Pressure
timeFrame: 3 months
measure: Incidence of clinical decompensation
timeFrame: 1 year
measure: Overall Improvement of Patient Reported outcome
timeFrame: 6 months
measure: Overall Improvement of MELD score
timeFrame: 1 year
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: National University Hospital, Singapore
name: Dan Yock Young
role: PRINCIPAL_INVESTIGATOR
affiliation: National University Hospital, Singapore
name: Mark Muthiah
role: PRINCIPAL_INVESTIGATOR
References: