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G-CSF in Decompensated Cirrhosis: an Open Label Trial

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ClinicalTrials.gov Identifier: NCT03415698
Recruitment Status : 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

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.


Condition or disease Intervention/treatment Phase
Cirrhosis, Liver Drug: G-CSF Drug: Standard Medical Therapy Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Granulocyte Colony Stimulating Factor in Decompensated Cirrhosis: an Open Label Study
Actual Study Start Date : July 2016
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis

Arm Intervention/treatment
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)
Drug: Standard Medical Therapy
Nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics.

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.
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.




Primary Outcome Measures :
  1. Survival [ Time Frame: One year ]
    Survival at 1 year after start of therapy


Secondary Outcome Measures :
  1. Hemopoieticstem cell mobilisation [ Time Frame: One Year ]
    Mobilisation of CD 34+ cells in peripheral blood

  2. Clinical improvement in liver functions [ Time Frame: One Year ]
    Occurrence of decompensations namely ascites, hepatic encephalopathy and variceal bleed

  3. Biochemical improvement in liver functions [ Time Frame: One year ]
    Improvment in MELD score

  4. 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

  5. Improvement in quality of life [ Time Frame: One year ]
    Quality of life will be assessed using SF-36V2 Health Survey questionnaire

  6. Safety of G-CSF as assessed by its adverse effects [ Time Frame: One Year ]


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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 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

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): NCT03415698


Contacts
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Contact: Virendra Singh, DM 7087009338 virendrasingh100@hotmail.com
Contact: Arka De, MD 9999816539 arkascore@gmail.com

Locations
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India
Post Graduate Institute of Medical Education and Research Recruiting
Chandigarh, India, 160012
Contact: Virendra Singh, DM    7087009338    virendrasingh100@hotmail.com   
Contact: Arka De, MD    9999816539    arkascore@gmail.com   
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research
Investigators
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Principal Investigator: Virendra Singh, DM Professor, Department of Hepatology, PGIMER, Chandigarh

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Responsible Party: Dr.Virendra Singh, Professor of Hepatology, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT03415698     History of Changes
Other Study ID Numbers: GCSF in cirrhosis
First Posted: January 30, 2018    Key Record Dates
Last Update Posted: January 30, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

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

Additional relevant MeSH terms:
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Fibrosis
Liver Cirrhosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs