Ignite Creation Date:
2024-05-06 @ 1:02 PM
Last Modification Date:
2024-10-26 @ 1:07 PM
Study NCT ID:
NCT03911037
Status:
UNKNOWN
Last Update Posted:
2019-07-19
First Post:
2019-04-06
Brief Title:
GCSF Therapy in Decompensated Cirrhosis - A Double Blinded RCT
Sponsor:
Post Graduate Institute of Medical Education and Research Chandigarh
Organization:
PGIMER
Study Overview
Official Title:
Granulocyte Colony Stimulating Factor Therapy In Decompensated Cirrhosis Of Liver A Double Blinded Single Centre Randomised Controlled Trial
Status:
UNKNOWN
Status Verified Date:
2019-07
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Cirrhosis of liver is a leading cause of morbidity and mortality worldwide Complications like ascites spontaneous bacterial peritonitis variceal bleed hepatic encephalopathy hepatorenal syndrome HRS and hepatocellular carcinoma HCC portend a poor prognosis and further decreases survival in these patients The major causes of cirrhosis include excessive alcohol consumption viral hepatitis and non- alcoholic fatty liver disease
Currently the only definitive treatment option for cirrhosis is liver transplantation which is limited in its applicability due to donor shortage exorbitant costs and lack of widespread availability Moreover it requires lifelong immunosuppression and has considerable long term side effects including chronic renal failure post-transplant lymphoproliferative disease and cardiovascular complications
The ability of stem cells to differentiate into multiple cellular lineages makes one speculate that stem cells can be used for tissue repair and regeneration when tissue-resident stem cells become overwhelmed It has been shown that in response to acute or chronic liver damage bone marrow derived stem cells can spontaneously populate the liver and differentiate into hepatic cells thereby contributing to hepatic regeneration Thus apart from hepatocytes and intrahepatic stem cells bone marrow derived stem cells also participate in the liver regeneration process
Currently there are two methods to mobilize stem cells from the bone marrow to the liver One is administration of cytokines like granulocyte-colony stimulating factor G-CSF and the other is the isolation of stem cells from the marrow and their injection into the hepatic artery or portal vein after purification The latter is probably more cumbersome and may be potentially risky due to the underlying coagulation abnormalities in cirrhotic patients Improved liver histology and survival has been noted in patients with cirrhosis following mobilization of bone marrow stem cells by granulocyte-colony stimulating factor G-CSF
Three recent studies have demonstrated G-CSF induced mobilization of bone marrow stem cells CD34 cells in peripheral blood and their subsequent increase in liver tissue and improved survival in patients with alcoholic hepatitis and ACLF However there is a paucity of data on whether G-CSF improves survival and prognosis in patients with decompensated cirrhosis
Verma Singh et al have shown in an open label trial that there was significantly better 12 month transplant free survival in GCSF Growth hormone standard medical therapy group and G CSF standard medical therapy group as compared to standard medical therapy group alone CD 34 cells at day 6 of therapy increased as compared to baseline There was also a significant decrease of clinical scores improvement in nutrition better control of ascites reduction in liver stiffness lesser episodes of infection as well as improvement in QOL scores in the treatment groups having G CSF as compared to baseline
In a recent study by Newsome et al a multicentre open label randomized phase 2 trial patients were randomized to standard care treatment with subcutaneous G CSF or treatment with G CSF for 5 days followed by leukaphersis and IV infusion of CD 133 positive haematopoietic stem cells They did not find any difference in MELD score over time in all 3 treatment groups Serious adverse effects were more common in the G CSF groups than in standard treatment group
In a study by Kedarisetty CK et al a significantly larger proportion of patients with decompensated cirrhosis given a combination of G-CSF Darbopoietin α survived for 12 months more than patients given only placebo 68 vs 269 P 0001 The combination therapy also reduced liver severity scores and sepsis to a greater extent than placebo
In view of the conflicting results of the above studies and no studies on the use of multiple courses of GCSF in patients with decompensated cirrhosis in a double blind manner the present study was undertaken to assess the safety and efficacy of G-CSF in patients with decompensated cirrhosis in the form of a double blinded RCT
Currently the only definitive treatment option for cirrhosis is liver transplantation which is limited in its applicability due to donor shortage exorbitant costs and lack of widespread availability Moreover it requires lifelong immunosuppression and has considerable long term side effects including chronic renal failure post-transplant lymphoproliferative disease and cardiovascular complications
The ability of stem cells to differentiate into multiple cellular lineages makes one speculate that stem cells can be used for tissue repair and regeneration when tissue-resident stem cells become overwhelmed It has been shown that in response to acute or chronic liver damage bone marrow derived stem cells can spontaneously populate the liver and differentiate into hepatic cells thereby contributing to hepatic regeneration Thus apart from hepatocytes and intrahepatic stem cells bone marrow derived stem cells also participate in the liver regeneration process
Currently there are two methods to mobilize stem cells from the bone marrow to the liver One is administration of cytokines like granulocyte-colony stimulating factor G-CSF and the other is the isolation of stem cells from the marrow and their injection into the hepatic artery or portal vein after purification The latter is probably more cumbersome and may be potentially risky due to the underlying coagulation abnormalities in cirrhotic patients Improved liver histology and survival has been noted in patients with cirrhosis following mobilization of bone marrow stem cells by granulocyte-colony stimulating factor G-CSF
Three recent studies have demonstrated G-CSF induced mobilization of bone marrow stem cells CD34 cells in peripheral blood and their subsequent increase in liver tissue and improved survival in patients with alcoholic hepatitis and ACLF However there is a paucity of data on whether G-CSF improves survival and prognosis in patients with decompensated cirrhosis
Verma Singh et al have shown in an open label trial that there was significantly better 12 month transplant free survival in GCSF Growth hormone standard medical therapy group and G CSF standard medical therapy group as compared to standard medical therapy group alone CD 34 cells at day 6 of therapy increased as compared to baseline There was also a significant decrease of clinical scores improvement in nutrition better control of ascites reduction in liver stiffness lesser episodes of infection as well as improvement in QOL scores in the treatment groups having G CSF as compared to baseline
In a recent study by Newsome et al a multicentre open label randomized phase 2 trial patients were randomized to standard care treatment with subcutaneous G CSF or treatment with G CSF for 5 days followed by leukaphersis and IV infusion of CD 133 positive haematopoietic stem cells They did not find any difference in MELD score over time in all 3 treatment groups Serious adverse effects were more common in the G CSF groups than in standard treatment group
In a study by Kedarisetty CK et al a significantly larger proportion of patients with decompensated cirrhosis given a combination of G-CSF Darbopoietin α survived for 12 months more than patients given only placebo 68 vs 269 P 0001 The combination therapy also reduced liver severity scores and sepsis to a greater extent than placebo
In view of the conflicting results of the above studies and no studies on the use of multiple courses of GCSF in patients with decompensated cirrhosis in a double blind manner the present study was undertaken to assess the safety and efficacy of G-CSF in patients with decompensated cirrhosis in the form of a double blinded RCT
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None