G-CSF in Decompensated Cirrhosis: an Open Label Trial

NCT03415698 | Unknown Phase 2

• 1 other identifier: GCSF in cirrhosis
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Cirrhosis, Liver

Keywords

Regenerative medicine

Outcome Measures

Primary Outcomes (1)

• Survival

  Survival at 1 year after start of therapy

  One year

Secondary Outcomes (6)

• Hemopoieticstem cell mobilisation

  One Year

• Clinical improvement in liver functions

  One Year

• Biochemical improvement in liver functions

  One year

• Improvement in nutritional status

  One Year

• Improvement in quality of life

  One year

Study Arms (2)

Standard Medical Therapy

ACTIVE COMPARATOR

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

G-CSF + Standard Medical Therapy

ACTIVE COMPARATOR

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; Drug: Standard Medical Therapy

Interventions

G-CSF DRUG

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.

G-CSF + Standard Medical Therapy

Standard Medical Therapy DRUG

Nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics.

G-CSF + Standard Medical Therapy; Standard Medical Therapy

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 irrespective of etiology

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Post Graduate Institute of Medical Education and Research

Chandigarh, 160012, India

RECRUITING

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

• 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.

  PMID: 32088302 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; 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

Study Officials

• Virendra Singh, DM

  Professor, Department of Hepatology, PGIMER, Chandigarh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Virendra Singh, DM

CONTACT

7087009338; virendrasingh100@hotmail.com

Arka De, MD

CONTACT

9999816539; arkascore@gmail.com

Study Design

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

Study Record Dates

• First Submitted: January 11, 2018
• First Posted: January 30, 2018
• Study Start: July 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: December 1, 2018
• Last Updated: January 30, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)