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.

Not Applicable

Not yet recruiting

• Conditions: Decompensated Liver Cirrhosis
• Interventions: Drug: Lactulose; Drug: Darbepoetin; Biological: Albumin; Drug: G-CSF

• Registration Number: NCT07002827
• Lead Sponsor: Institute of Liver and Biliary Sciences, India

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.

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-03
• Study First Submitted QC: 2025-05-26
• Last Update Submitted: 2025-05-26
• Study Start: 2025-05-30
• Study First Posted: 2025-06-04
• Last Update Posted: 2025-06-04
• Primary Completion: 2026-04-30
• Study Completion: 2026-04-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Medical treatment	Lactulose	Standard medical therapy including lactulose, bowel enema and albumin will be continued in both groups.
Standard Medical treatment	Albumin	Standard medical therapy including lactulose, bowel enema and albumin will be continued in both groups.
Single cycle of G-CSF + darbepoetin and standard medical treatment	Darbepoetin	* G-CSF will be given at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30. * Darbepoetin will be given s/c at dose of 40 mcg once a week (total 4 doses) for 1 month. * Standard medical therapy including lactulose, bowel enema and albumin will be continued in both groups.
Single cycle of G-CSF + darbepoetin and standard medical treatment	G-CSF	* G-CSF will be given at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30. * Darbepoetin will be given s/c at dose of 40 mcg once a week (total 4 doses) for 1 month. * Standard medical therapy including lactulose, bowel enema and albumin will be continued in both groups.
Single cycle of G-CSF + darbepoetin and standard medical treatment	Lactulose	* G-CSF will be given at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30. * Darbepoetin will be given s/c at dose of 40 mcg once a week (total 4 doses) for 1 month. * Standard medical therapy including lactulose, bowel enema and albumin will be continued in both groups.
Single cycle of G-CSF + darbepoetin and standard medical treatment	Albumin	* G-CSF will be given at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30. * Darbepoetin will be given s/c at dose of 40 mcg once a week (total 4 doses) for 1 month. * Standard medical therapy including lactulose, bowel enema and albumin will be continued in both groups.
Three cycles of G-CSF + darbepoetin and standard medical treatment (1-month, 3-month, and 5-month)	Darbepoetin	* G-CSF will be given at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30. * Darbepoetin will be given s/c at dose of 40 mcg once a week (total 4 doses) for 1 month. * Standard medical therapy including lactulose, bowel enema and albumin will be continued in both groups.
Three cycles of G-CSF + darbepoetin and standard medical treatment (1-month, 3-month, and 5-month)	G-CSF	* G-CSF will be given at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30. * Darbepoetin will be given s/c at dose of 40 mcg once a week (total 4 doses) for 1 month. * Standard medical therapy including lactulose, bowel enema and albumin will be continued in both groups.
Three cycles of G-CSF + darbepoetin and standard medical treatment (1-month, 3-month, and 5-month)	Lactulose	* G-CSF will be given at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30. * Darbepoetin will be given s/c at dose of 40 mcg once a week (total 4 doses) for 1 month. * Standard medical therapy including lactulose, bowel enema and albumin will be continued in both groups.
Three cycles of G-CSF + darbepoetin and standard medical treatment (1-month, 3-month, and 5-month)	Albumin	* G-CSF will be given at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30. * Darbepoetin will be given s/c at dose of 40 mcg once a week (total 4 doses) for 1 month. * Standard medical therapy including lactulose, bowel enema and albumin will be continued in both groups.

Primary Outcome Measures

Name	Time	Method
Change in innate immunity between the groups.	6 months	Innate immunity -Monocyte, neutrophils -distribution , function and bioenergetic adaptation

Secondary Outcome Measures

Name	Time	Method
Proportion of participants developed new-onset of LRE (such as ascites, HE, AKI, bleed and sepsis) or show mortality in all the groups.	6 months
Cumulative incidence of second decompensation in all the groups.	6 months & 1 year
Transplant-free survival.	6 months & 1 year
Number of participants with improvement in liver disease severity indices (CTP).	6 months
Number of participants with improvement in liver disease severity indices (MELD).	6 months
Number of participants with change in adaptive immunity(T-cell, B-cell and NK cells distribution only )	6 months
Number of participants with change in inflammation (a panel of pro and anti-inflammatory cytokines).	6 months
Change in gcsf levels and EPO levels at baseline and completion of each cycle.	6 months
Proportion of participants completing treatment without major adverse effects;	6 months
Number of participants with change in peripheral blood CD34+ Hematopoietic Stem Cells count at 6months.	6 months

Trial Locations

Locations (1)

Institute of Liver & Biliary Sciences (ILBS); 🇮🇳 New Delhi, Delhi, India