Autologous Endothelial Progenitor Cell Therapy for Reversal of Liver Cirrhosis

Autologous Endothelial Progenitor Cell Therapy for Reversal of Liver Cirrhosis

Sponsoren

Hauptsponsor: National University Hospital, Singapore

Mitarbeiter: Singapore General Hospital
Tan Tock Seng Hospital
Changi General Hospital

Quelle National University Hospital, Singapore
Kurze Zusammenfassung

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.

detaillierte Beschreibung

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.

Gesamtstatus Recruiting
Anfangsdatum April 15, 2017
Fertigstellungstermin March 31, 2021
Primäres Abschlussdatum March 31, 2020
Phase Phase 3
Studientyp Interventional
Primärer Ausgang
Messen Zeitfenster
Improvement of Fibrosis Staging (Ishak) 3 months
Improvement of liver fibrosis on MRE (magnetic resonance elastography) 6 months
Improvement of MELD (Model of End stage Liver Disease) score or Child Pugh State 6 months
Improvement of quantitative fibrosis 1 year
Sekundäres Ergebnis
Messen Zeitfenster
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
Overall Improvement of MELD score 1 year
Einschreibung 66
Bedingung
Intervention

Interventionsart: Drug

Interventionsname: Neupogen

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

Anderer Name: GCSF

Interventionsart: Procedure

Interventionsname: CD133 Cells Transplantation

Beschreibung: 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.

Armgruppenetikett: Treatment

Anderer Name: Endothelial Progenitor cells

Teilnahmeberechtigung

Kriterien:

Inclusion Criteria:

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

- Childs B/C with Child-Pugh score > 8

- MELD score 13-27

- Platelet>50 000/mls

Exclusion Criteria:

- MELD score >27

- Abdominal ascites precluding percutaneous transhepatic cannulation.

- HIV

- History of hematological or hepatic malignancy

- Other underlying malignancy with <1 year survival

- Absence of systemic diseases that may impact survival within 1 year.

- Listed or potential for liver transplant

- Pregnant women

Geschlecht: All

Mindestalter: 40 Years

Maximales Alter: 70 Years

Gesunde Freiwillige: No

Insgesamt offiziell
Gesamtkontakt

Nachname: Nur Halisah

Telefon: 66015193

Email: [email protected]

Ort
Einrichtung: Status: Ermittler: National University Hospital Dan Yock Young Principal Investigator Mark Muthiah Sub-Investigator
Standort Länder

Singapore

Überprüfungsdatum

February 2017

Verantwortliche Partei

Art: Sponsor

Hat den Zugriff erweitert No
Bedingung Durchsuchen
Anzahl der Waffen 2
Armgruppe

Etikette: Treatment

Art: Experimental

Beschreibung: Patient will undergo CD133+ cells transplantation at stable compensated state. 5 dose GCSF (Neupogen) 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.

Etikette: Control

Art: Active Comparator

Beschreibung: Non-Transplant Arm: Patients will receive 5 doses of GCSF (Neupogen)

Studiendesign Info

Zuweisung: Randomized

Interventionsmodell: Parallel Assignment

Beschreibung des Interventionsmodells: 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

Hauptzweck: Treatment

Maskierung: Single (Outcomes Assessor)

Maskierungsbeschreibung: 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.

Quelle: ClinicalTrials.gov