Clinical trial NCT07002827: Effect of Single vs Repeated Cycles of a Combination of Granulocyte Colony Stimulating Factor and Darbepoetin vs Standard Medical Treatment on Immunometabolic Profile in Patient With Early Decompensated Cirrhosis.
Official title: Effect of Single vs Repeated Cycles of a Combination of Granulocyte Colony Stimulating Factor and Darbepoetin vs Standard Medical Treatment on Immunometabolic Profile in Patient With Early Decompensated Cirrhosis -A Pilot Randomised Controlled Trial.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Decompensated Liver Cirrhosis
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2025-06-04
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Exogenous growth factor-mobilized bone marrow (BM) stem cells(G-CSF) and DARBEPOETIN use have shown a differential response in the management of decompensated cirrhosis (DC) with improved survival, CTP and MELD scores. This study was designed to evaluate potential clinical benefit of repeated cycles of granulocyte-colony stimulating factor (G-CSF) and DARBEPOETIN versus single cycle on delta change in immunometabolic profile of patients at 6 months assessed in terms of -Change in innate immunity -Monocyte, neutrophils -distribution , function and bioenergetic adaptation .

Detailed description: Aim: To study the efficacy of single vs repeated cycle of Granulocyte Colony Stimulating Factor+ darbopoetin vs standard medical treatmenton immunometabolic profile in patient with early decompensated cirrhosis

Study population:

* Age 18-70 years
* Early decompensated cirrhosis MELD \< 16 , CTP \< 9B
* Uncomplicated ascites
* A Prospective Randomized Controlled Trial.
* Single Centre.
* Open label.
* Block Randomization will be done , it will be implemented by IWRS method.
* The study will be conducted in Department of Hepatology, ILBS.

Eligibility criteria: Inclusion Criteria:

1. Age 18-70 years
2. Decompensated cirrhosis patients
3. Uncomplicated ascites,
4. CTP ≤ 9B and MELD \<16
5. BM Hematopoietic stem cell reserve \> 0.4
6. Given informed consent

Exclusion Criteria:

1. Patients with age less than 18 years or more than 65 years
2. Lack of informed consent
3. Patients with a history of serious allergic reactions to the active component, filgrastim, other human granulocyte colony-stimulating factors, or any of the ingredients
4. Evidence of alcoholic hepatitis/active alcohol abuse last intake ≤ 3 months
5. Suspected autoimmune hepatitis (ANA/ASMA-positive in titers 1:80 and/ or IgG 1.5 times upper limit of normal),
6. Hemolytic anaemia -Sickle cell disease or thalassemia
7. Patients with Grade III ascites /complicated ascites
8. Patients with large spleen (size ≥ 15cm)
9. Recent variceal bleeding in less than 42 days
10. Patients with any focus of sepsis as proven by culture positivity or presence of spontaneous Bacterial Peritonitis (SBP)
11. H/o Seizures
12. Hepatocellular Carcinoma (HCC) or other malignancy
13. Acute Kidney Injury (AKI) with serum Creatinine \>1.5 mg/ dl,
14. Multi-organ failure,
15. Hepatic Encephalopathy or prior history of HE in less than 6months
16. HIV seropositivity,
17. Uncontrolled essential hypertension, CAD /Stroke
18. Massive hydrothorax
19. Pregnancy
20. Viral etiology of liver disease
21. Chronic kidney disease
22. Portal vein thrombosis
23. Planned for LT
24. Bone marrow hematopoietic stem cells \< 0.4

Primary outcomes:
measure: Change in innate immunity between the groups.
timeFrame: 6 months
Secondary outcomes:
measure: Proportion of participants developed new-onset of LRE (such as ascites, HE, AKI, bleed and sepsis) or show mortality in all the groups.
timeFrame: 6 months
measure: Cumulative incidence of second decompensation in all the groups.
timeFrame: 6 months & 1 year
measure: Transplant-free survival.
timeFrame: 6 months & 1 year
measure: Number of participants with improvement in liver disease severity indices (CTP).
timeFrame: 6 months
measure: Number of participants with improvement in liver disease severity indices (MELD).
timeFrame: 6 months
measure: Number of participants with change in adaptive immunity(T-cell, B-cell and NK cells distribution only )
timeFrame: 6 months
measure: Number of participants with change in inflammation (a panel of pro and anti-inflammatory cytokines).
timeFrame: 6 months
measure: Change in gcsf levels and EPO levels at baseline and completion of each cycle.
timeFrame: 6 months
measure: Proportion of participants completing treatment without major adverse effects;
timeFrame: 6 months
measure: Number of participants with change in peripheral blood CD34+ Hematopoietic Stem Cells count at 6months.
timeFrame: 6 months
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of Liver & Biliary Sciences (ILBS)
state: Delhi
Study officials:
affiliation: Institute of Liver and Biliary Sciences
name: Dr Manoj Kumar Sharma, DM
role: STUDY_DIRECTOR
References: