Autologous Endothelial Progenitor Cell Therapy for Reversal of Liver Cirrhosis

NCT03109236 | Unknown Phase 3 DMC

• 1 other identifier: 2016/00711
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

End Stage Liver Disease

Outcome Measures

Primary Outcomes (4)

• Improvement of Fibrosis Staging (Ishak)

  Improvement of Fibrosis Staging (Ishak) \> 1 point

  3 months

• Improvement of liver fibrosis on MRE (magnetic resonance elastography)

  Improvement of liver fibrosis on MRE (magnetic resonance elastography) \> 2 point

  6 months

• 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

• Improvement of quantitative fibrosis

  Improvement of quantitative fibrosis on histology \> 10%

  1 year

Secondary Outcomes (6)

• Overall Survival and Improvement

  1 year

• Overall Improvement in Liver Function Tests

  1 year

• Improvement of Hepatic Venous Pressure

  3 months

• Incidence of clinical decompensation

  1 year

• Overall Improvement of Patient Reported outcome

  6 months

Study Arms (2)

Treatment

EXPERIMENTAL

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.

Drug: GCSF; Procedure: CD133 Cells Transplantation

Control

ACTIVE COMPARATOR

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

Drug: GCSF

Interventions

GCSF DRUG

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

Control; Treatment

CD133 Cells Transplantation PROCEDURE

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.

Also known as: Endothelial Progenitor cells

Treatment

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• MELD score 10-27
• Clinically significant portal hypertension as evidenced by gastroesophageal varices or ascites

You may not qualify if:

• 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

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Singapore General Hospital: collaborator
• Tan Tock Seng Hospital: collaborator
• Changi General Hospital: collaborator

Study Sites (1)

National University Hospital

Singapore, 119074, Singapore

RECRUITING

MeSH Terms

Conditions

End Stage Liver Disease

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Officials

• Dan Yock Young

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

• Mark Muthiah

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nur Halisah

CONTACT

66015193; mdcnhj@nus.edu.sg

Dan Yock Young

CONTACT

67727641; yock_young_dan@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinding will be maintained by investigators performing analysis of the results. Given the invasive procedure of percutaneous transhepatic cannulation, the investigators felt that it will be unethical to perform sham procedure on control arm patients. Both managing doctors and patient will know which arm they are on but where not inevitable, data collection such as quality of life and results interpretation such as histology and laboratory analysis of results will be performed anonymously.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: April 12, 2017
• Study Start: August 24, 2017
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: January 19, 2021

Record last verified: 2021-01

Locations

SG (1)