G-CSF in Decompensated Cirrhosis: an Open Label Trial

Post Graduate Institute of Medical Education and Research, Chandigarh

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Cirrhosis, Liver

Treatments: Drug: Standard Medical Therapy; Drug: G-CSF

Study type: Interventional

Funder types: Other

Identifiers

NCT03415698

GCSF in cirrhosis

Details and patient eligibility

About

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 2 patient groups

Standard Medical Therapy

Active Comparator group

Description:

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)

Treatment:

Drug: Standard Medical Therapy

G-CSF + Standard Medical Therapy

Active Comparator group

Description:

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.

Treatment:

Drug: Standard Medical Therapy

Drug: G-CSF