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Granulocyte Colony Stimulating Factor And Growth Hormone In Cirrhosis Of Liver: An Open Label Study

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ClinicalTrials.gov Identifier: NCT02451033
Recruitment Status : Completed
First Posted : May 21, 2015
Last Update Posted : August 29, 2017
Sponsor:
Information provided by (Responsible Party):
Dr.Virendra Singh, Postgraduate Institute of Medical Education and Research

Brief Summary:

Cirrhosis of liver is a leading cause of morbidity and mortality worldwide . Complications including ascites, spontaneous bacterial peritonitis (SBP), variceal bleed, hepatic encephalopathy, hepatorenal syndrome (HRS) and development of hepatocellular carcinoma (HCC) have poor prognosis and further decreases the survival in these patients. It has been believed that cirrhosis is irreversible and that treatment should focus on preventing the progression of liver fibrosis/dysfunction and its complications.

Currently the only effective treatment is liver transplantation, an increasingly limited and expensive resource especially in developing countries. Furthermore, transplantation comes with a requirement for lifelong immunosuppression, and considerable long-term side effects that include chronic renal failure, post-transplant lymphoproliferative disease, and cardiovascular complications.

Short of liver transplant, recently, reports of unexpected plasticity in adult bone marrow have raised hopes that stem cell therapy may offer exciting therapeutic possibilities for patients with end stage liver diseases. 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. Animal and human studies suggested that such cells might contribute to the regeneration after different kinds of liver injuries . In animal models, after liver injury, bone marrow-derived circulating pluripotent cells have been reported to participate in liver repopulation with both non-parenchymal cells and hepatocytes. This repopulation process, however, seems to be highly dependent on the type of liver injury and experimental conditions. Fusion with hematopoietic cells has been substantiated as a mechanism by which hepatocytes can regenerate, and studies have demonstrated improved liver histology and survival 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 acute on chronic liver failure (ACLF) . However there is insufficient data on whether G-CSF improves survival and prognosis in patients with cirrhosis.

Also, Malnutrition is commonly seen (60-70%) in cirrhotics and have adverse prognosis on its outcome . The protein catabolic state of cirrhosis is associated with severe growth hormone (GH) resistance, with low levels of insulin-like growth factor (IGF)-I and its major binding protein (IGFBP)-3 . GH therapy in cirrhosis have been shown to improve nitrogen economy and to improve the GH resistance in a small pilot study. Also, GH therapy of short duration has shown to increase IGF1 levels, IGFBP-3 levels in patients of cirrhosis . GH therapy has also shown to improve liver regeneration and protein synthesis after hepatectomy in patients of HCC with cirrhosis . However there is scarcity of data on clinical impact of long term administration of GH therapy in patients of cirrhosis.


Condition or disease Intervention/treatment Phase
Cirrhosis Drug: standard medical therapy Drug: G-CSF Drug: Growth Hormone Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Granulocyte Colony Stimulating Factor And Growth Hormone In Cirrhosis Of Liver: An Open Label Study
Actual Study Start Date : May 2015
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016


Arm Intervention/treatment
Active Comparator: standard medical therapy
Standard medical therapy
Drug: standard medical therapy
diuretics, albumin infusion, antibiotics, nutrition, and variceal banding wherever needed

Active Comparator: G-CSF
Standard medical therapy plus G-CSF at the dosage of 5 µg/Kg subcutaneously every 12 hr for five consecutive days then every 3 monthly for 3 days till 1 year.
Drug: standard medical therapy
diuretics, albumin infusion, antibiotics, nutrition, and variceal banding wherever needed

Drug: G-CSF
G-CSF at the dosage of 5 µg/Kg subcutaneously every 12 hr for five consecutive days then every 3 monthly for 3 days till 1 year

Active Comparator: G-CSF plus growth hormone
Standard medical therapy plus G-CSF plus Growth Hormone therapy. Growth Hormone will be given in low dose of 1unit sc daily for 1 year.
Drug: standard medical therapy
diuretics, albumin infusion, antibiotics, nutrition, and variceal banding wherever needed

Drug: G-CSF
G-CSF at the dosage of 5 µg/Kg subcutaneously every 12 hr for five consecutive days then every 3 monthly for 3 days till 1 year

Drug: Growth Hormone
Growth Hormone in low dose of 1unit sc daily for 1 year




Primary Outcome Measures :
  1. Transplant free survival [ Time Frame: 1 year ]
    Survival at 1 year from the onset of therapy


Secondary Outcome Measures :
  1. haematopoietic stem cell mobilization [ Time Frame: 1 year ]
    Mobilisation of CD34+ cells in peripheral blood

  2. safety as measured by adverse effects of G-CSF, GH and combination in cirrhosis of liver [ Time Frame: 1 year ]
    Adverse effects of G-CSF, GH and combination in cirrhosis of liver

  3. Clinical/biochemical improvement in liver function profile [ Time Frame: 1 year ]
    Improvement in prognostic scores - MELD score, and Child score



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Decompensated Cirrhosis of liver.

Exclusion Criteria:

  • Acute on chronic liver failure
  • Spleen diameter of larger than 180 mm
  • Diagnosis of concomitant hepatocellular carcinoma or other active malignancy
  • Upper gastrointestinal bleed due to portal hypertension in the previous 7 days
  • Recent episode of portal vein thrombosis
  • Severe renal dysfunction creatinine (>1.5mg/dl)
  • Severe cardiac dysfunction
  • Uncontrolled diabetes or diabetic retinopathy
  • Acute infection or disseminate intravascular coagulation
  • Active alcohol abuse in last 3months
  • Known hypersensitivity to G-CSF and GH
  • Human immunodeficiency virus seropositivity
  • Pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02451033


Locations
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India
Dept. of Hepatology, PGIMER, Chandigarh
Chandigarh, India, 160012
Department of Hepatology,Postgraduate Institute of Medical Education and Research
Chandigarh, India
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research
Investigators
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Principal Investigator: Virendra Singh, MD;DM Professor of Hepatology,PGIMER,Chandigarh

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Dr.Virendra Singh, Professor of Hepatology, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT02451033     History of Changes
Other Study ID Numbers: G-CSF and GH in cirrhosis
First Posted: May 21, 2015    Key Record Dates
Last Update Posted: August 29, 2017
Last Verified: August 2017

Keywords provided by Dr.Virendra Singh, Postgraduate Institute of Medical Education and Research:
Regenerative medicine

Additional relevant MeSH terms:
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Liver Cirrhosis
Pathologic Processes
Liver Diseases
Fibrosis
Digestive System Diseases
Hormones
Lenograstim
Sargramostim
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Adjuvants, Immunologic
Immunologic Factors