We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

G-CSF in Decompensated Cirrhosis: an Open Label Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03415698
Recruitment Status : Unknown
Verified January 2018 by Dr.Virendra Singh, Postgraduate Institute of Medical Education and Research.
Recruitment status was:  Recruiting
First Posted : January 30, 2018
Last Update Posted : January 30, 2018
Sponsor:
Information provided by (Responsible Party):
Dr.Virendra Singh, Postgraduate Institute of Medical Education and Research

Tracking Information
First Submitted Date  ICMJE January 11, 2018
First Posted Date  ICMJE January 30, 2018
Last Update Posted Date January 30, 2018
Actual Study Start Date  ICMJE July 2016
Estimated Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2018)
Survival [ Time Frame: One year ]
Survival at 1 year after start of therapy
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2018)
  • Hemopoieticstem cell mobilisation [ Time Frame: One Year ]
    Mobilisation of CD 34+ cells in peripheral blood
  • Clinical improvement in liver functions [ Time Frame: One Year ]
    Occurrence of decompensations namely ascites, hepatic encephalopathy and variceal bleed
  • Biochemical improvement in liver functions [ Time Frame: One year ]
    Improvment in MELD score
  • Improvement in nutritional status [ Time Frame: One Year ]
    Nutritional status will be assesses by skeletal muscle index measurement using CT scan measurements at L3 level
  • Improvement in quality of life [ Time Frame: One year ]
    Quality of life will be assessed using SF-36V2 Health Survey questionnaire
  • Safety of G-CSF as assessed by its adverse effects [ Time Frame: One Year ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE G-CSF in Decompensated Cirrhosis: an Open Label Trial
Official Title  ICMJE Granulocyte Colony Stimulating Factor in Decompensated Cirrhosis: an Open Label Study
Brief Summary

Globally, cirrhosis is the fifth commonest cause of mortality. Its natural history is typified by an initial, largely asymptomatic, "compensated" phase followed by "decompensation" due to complications of raised portal pressures and hepatocellular dysfunction.

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. The need for long term immunosuppression and its attendant complications are a further drawback. The ability of stem cells to differentiate into multiple cellular lineages makes one speculate that they can be used for tissue repair and regeneration when tissue-resident stem cells become overwhelmed. Bone marrow derived stem cells have amazing plasticity. They can "home" to the liver in response to injury and help in liver regeneration by trans-differentiation, cell fusion and augmentation of tissue- resident stem cell mediated repair. Two methods are available for the mobilisation of stem cells from the bone marrow to the liver. One involves the administration of cytokines like granulocyte-colony stimulating factor (G-CSF) and the other is the isolation of stem cells from the marrow followed by 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 .

G-CSF has been shown to mobilise bone marrow stem cells and even increase survival in patients of severe alcoholic steatohepatitis and ACLF. There is conflicting evidence on the role of G-CSF in decompensated cirrhosis with some studies showing improved survival while others have shown a lack of clinical or biochemical benefit. Many of these studies have used a single course of G-CSF. Verma et al, in a recent study published in 2018, elegantly demonstrated the beneficial effect of multiple courses of G-CSF in improving mortality and transplant free survival in decompensated cirrhotics.

The investigators too speculate that multiple cycles of G-CSF could result in better outcomes in decompensated cirrhosis by causing more prolonged and sustained stem cell homing to the liver. Thus, this study is being undertaken to further evaluate the safety and efficacy of multiple cycles of G-CSF in decompensated cirrhotics.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cirrhosis, Liver
Intervention  ICMJE
  • Drug: G-CSF
    G-CSF will be administered at the dosage of 5 µg/Kg subcutaneously every 12 hr for five consecutive days. four such cycles will be administered at three monthly intervals.
  • Drug: Standard Medical Therapy
    Nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics.
Study Arms  ICMJE
  • Active Comparator: Standard Medical Therapy
    Standard medical therapy will include nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins, antibiotics. fresh frozen plasma and packed red-cell transfusions (as required)
    Intervention: Drug: Standard Medical Therapy
  • Active Comparator: G-CSF + Standard Medical Therapy
    G-CSF at the dosage of 5 µg/Kg subcutaneously every 12 hr will be administered for five consecutive days. Four such cycles at 3 monthly intervals will be administered.
    Interventions:
    • Drug: G-CSF
    • Drug: Standard Medical Therapy
Publications * De A, Kumari S, Singh A, Kaur A, Sharma R, Bhalla A, Sharma N, Kalra N, Singh V. Multiple Cycles of Granulocyte Colony-Stimulating Factor Increase Survival Times of Patients With Decompensated Cirrhosis in a Randomized Trial. Clin Gastroenterol Hepatol. 2021 Feb;19(2):375-383.e5. doi: 10.1016/j.cgh.2020.02.022. Epub 2020 Feb 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: January 23, 2018)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2018
Estimated Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Decompensated Cirrhosis of liver irrespective of etiology

Exclusion Criteria:

  • Acute on chronic liver failure (fulfilling either APASL or CANONIC criteria of ACLF)
  • Splenic diameter of more than 18 cm
  • Concomitant HCC or other active malignancy
  • Upper gastrointestinal bleeding in the previous 7 days
  • Portal vein thrombosis
  • Severe renal dysfunction as defined by creatnine > 1.5mg/dl
  • Severe cardiac dysfunction
  • Uncontrolled diabetes (Hb A 1c ≥ 9) or diabetic retinopathy
  • Acute infection or disseminate intravascular coagulation
  • Active alcohol abuse in last 3 months
  • Known hypersensitivity to G-CSF
  • HIV co-infection
  • Pregnancy
  • Refusal to give informed consent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE India
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03415698
Other Study ID Numbers  ICMJE GCSF in cirrhosis
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Dr.Virendra Singh, Postgraduate Institute of Medical Education and Research
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Postgraduate Institute of Medical Education and Research
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Virendra Singh, DM Professor, Department of Hepatology, PGIMER, Chandigarh
PRS Account Postgraduate Institute of Medical Education and Research
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP