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

NCT02451033 | Completed Phase 2 DMC

• 1 other identifier: G-CSF and GH in cirrhosis
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 2

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.

Conditions

Cirrhosis

Keywords

Regenerative medicine

Outcome Measures

Primary Outcomes (1)

• Transplant free survival

  Survival at 1 year from the onset of therapy

  1 year

Secondary Outcomes (3)

• haematopoietic stem cell mobilization

  1 year

• safety as measured by adverse effects of G-CSF, GH and combination in cirrhosis of liver

  1 year

• Clinical/biochemical improvement in liver function profile

  1 year

Study Arms (3)

standard medical therapy

ACTIVE COMPARATOR

Standard medical therapy

Drug: standard medical therapy

G-CSF

ACTIVE COMPARATOR

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; Drug: G-CSF

G-CSF plus growth hormone

ACTIVE COMPARATOR

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; Drug: G-CSF; Drug: Growth Hormone

Interventions

standard medical therapy DRUG

diuretics, albumin infusion, antibiotics, nutrition, and variceal banding wherever needed

G-CSF; G-CSF plus growth hormone; standard medical therapy

G-CSF DRUG

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

G-CSF; G-CSF plus growth hormone

Growth Hormone DRUG

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

G-CSF plus growth hormone

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Decompensated Cirrhosis of liver.

You may not qualify if:

• 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

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (2)

Dept. of Hepatology, PGIMER, Chandigarh

Chandigarh, 160012, India

Location

Department of Hepatology,Postgraduate Institute of Medical Education and Research

Chandigarh, India

Location

Related Publications (2)

• Kaur A, Verma N, Singh B, Kumar A, Kumari S, De A, Sharma RR, Singh V. Quantitative liver SPECT/CT is a novel tool to assess liver function, prognosis, and response to treatment in cirrhosis. Front Med (Lausanne). 2023 Mar 22;10:1118531. doi: 10.3389/fmed.2023.1118531. eCollection 2023.

  PMID: 37035316 DERIVED

• Verma N, Kaur A, Sharma R, Bhalla A, Sharma N, De A, Singh V. Outcomes after multiple courses of granulocyte colony-stimulating factor and growth hormone in decompensated cirrhosis: A randomized trial. Hepatology. 2018 Oct;68(4):1559-1573. doi: 10.1002/hep.29763. Epub 2018 Jul 25.

  PMID: 29278428 DERIVED

MeSH Terms

Conditions

Fibrosis

Interventions

Granulocyte Colony-Stimulating Factor; Growth Hormone

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Virendra Singh, MD;DM

  Professor of Hepatology,PGIMER,Chandigarh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Hepatology

Study Record Dates

• First Submitted: May 12, 2015
• First Posted: May 21, 2015
• Study Start: May 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: August 29, 2017

Record last verified: 2017-08

Locations

IN (2)