A Trial to Study the Influence of Growth Factors on Bone Marrow and Hepatic Regeneration in Patients With Decompensated Cirrhosis.

This will be a randomized double blind study which will be conducted on patients admitted to Department of Hepatology from June 2013 to may 2014 at ILBS, New Delhi. Patients not having any exclusion criteria will undergo bone marrow examination and liver biopsy at the baseline.

60 patients of decompensated cirrhosis will be randomised into two limbs- limb A (30 patients) will receive G-CSF and erythropoietin while those on limb B (30 patients) will receive G-CSF alone. The drugs will be given for 2 months and patient will be followed for 1 year. G-CSF will be given at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every 3rd day till day 60 (total 22 doses). Erythropoietin will be given s/c at dose of 500 IU/Kg twice a week for 2 months.

Follow up will be done on days 0,3,7,14,28, day 42 (6 weeks), day 60 (2 months), day 90 (3 months), day 180 (6 months), day 270 (9 months); and day 360 (1 year).

Study Overview

• Status: Completed
• Conditions: Decompensated Cirrhosis
• Intervention / Treatment: Drug: G-CSF; Drug: G-CSF+Erythropoetin

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects aged 18-65 years
• All patients who are known to have cirrhosis of liver with portal hypertension and are compensated on presentation with no features of ascites/ jaundice/ bleed/ HE/ HRS.
• Only patients with alcoholic cirrhosis and cryptogenic cirrhosis (etiology work up negative) will be enrolled in the study.

Exclusion Criteria:

• Sepsis ( Any culture positive: blood, urine, any other obvious source of infection: UTI, LRTI)
• Variceal bleed in the past 3 months
• Autoimmune disorders
• HCC (Hepatocellular Carcinoma)
• Multi organ failure
• Any features of decompensation in form of ascites/Jaundice/ HE (grade 3 or 4) / HRS
• HIV seropositivity
• Essential hypertension
• Pregnancy
• Refusal to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: G-CSF + Erythropoietin	Drug: G-CSF
ACTIVE_COMPARATOR: G-CSF	Drug: G-CSF+Erythropoetin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary end point will be transplant free survival rate at 1 year in patients with decompensated cirrhosis.	1 Year

Secondary Outcome Measures

Outcome Measure	Time Frame
Histopathological evidence of hepatic regeneration and mobilization of CD34/stem cells	1 Year
Histopathological evidence of contribution of bone marrow precursor cells in hepatic regeneration and the markers predicting positive response to growth factors	1 Year
Development of new complications such as appearance or worsening of hepatic encephalopathy, hepatorenal syndrome and sepsis.	1 Year
Improvement in severity assessment scores and safety profile of G-CSF (Growth-Colony Stimulating Factor) + EPO (Erythropoetin)dual therapy vs. G-CSF alone.	1 Year
Transplant free survival at 6 months in both groups	6 months

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India
• Investigators: Principal Investigator: Dr Lovkesh Anand, MD, Institute of Liver & Biliary Sciences.

Publications and helpful links

General Publications

• Kumar D, Maheshwari D, Nautiyal N, Shubham S, Rooge S, Anand L, Vyas A, Kumari R, Sharma S, Bihari C, Mohanty S, Maiwall R, Kumar A, Sarin SK. Defects in energy metabolism are associated with functional exhaustion of bone marrow mesenchymal stem cells in cirrhosis. Am J Stem Cells. 2022 Feb 15;11(1):12-27. eCollection 2022.
• Anand L, Bihari C, Kedarisetty CK, Rooge SB, Kumar D, Shubham S, Kumar G, Sahney A, Sharma MK, Maiwall R, Kumar A, Sarin SK. Early cirrhosis and a preserved bone marrow niche favour regenerative response to growth factors in decompensated cirrhosis. Liver Int. 2019 Jan;39(1):115-126. doi: 10.1111/liv.13923. Epub 2018 Aug 10.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: July 15, 2013
• First Submitted That Met QC Criteria: July 17, 2013
• First Posted (ESTIMATE): July 18, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): November 22, 2016
• Last Update Submitted That Met QC Criteria: November 21, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Hematinics; Lenograstim; Epoetin Alfa
• Other Study ID Numbers: ILBS-Hepatic Regeneration -001