Clinical trial NCT03415698: G-CSF in Decompensated Cirrhosis: an Open Label Trial
Official title: Granulocyte Colony Stimulating Factor in Decompensated Cirrhosis: an Open Label Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Cirrhosis, Liver
Keywords: Regenerative medicine
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2018-01-30
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Survival
timeFrame: One year
Secondary outcomes:
measure: Hemopoieticstem cell mobilisation
timeFrame: One Year
measure: Clinical improvement in liver functions
timeFrame: One Year
measure: Biochemical improvement in liver functions
timeFrame: One year
measure: Improvement in nutritional status
timeFrame: One Year
measure: Improvement in quality of life
timeFrame: One year
measure: Safety of G-CSF as assessed by its adverse effects
timeFrame: One Year
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Education and Research
Study officials:
affiliation: Professor, Department of Hepatology, PGIMER, Chandigarh
name: Virendra Singh, DM
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.