search
Back to results

Granulocyte Colony Stimulating Factor Four Week Plus N-Acetyl Cysteine in Severe Alcoholic Hepatitis

Primary Purpose

Alcoholic Hepatitis

Status
Completed
Phase
Phase 4
Locations
India
Study Type
Interventional
Intervention
Standard Medical Therapy
G-CSF
G-CSF and NAC
Sponsored by
Postgraduate Institute of Medical Education and Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcoholic Hepatitis focused on measuring alcoholic hepatitis, alcoholic liver disease, regeneration

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria: • Alcoholic hepatitis patients(More than 10 years of heavy alcohol consumption (mean intake ≈ 100 g/day);Elevated aspartate aminotransferase level (but <500 IU per millilitre) and Ratio ofAST/ALT≥2 times;Elevated serum total bilirubin level ≥ 5 mgdL (86 μmol/L);Elevated INR(≥1.5) and;Neutrophilia. Patient with Maddrey's DF of≥ 32 will be included in the study, with or without biopsy) Exclusion Criteria: Age < 18 and > 75 years Hepatocellular carcinoma or portal vein thrombosis Refusal to participate in the study Serum creatinine >1.0 mg% Hepatic encephalopathy- grade 3 or 4 Upper gastrointestinal bleed in last ten days Uncontrolled bacterial infection Human immunodeficiency virus, Hepatitis B virus, Hepatitis C virus seropositivity, Autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha1-antitrypsin deficiency Pregnancy Glucocorticoid treatment Significant co-morbidity Previous known hypersensitivity to G-CSF/NAC

Sites / Locations

  • Dept of Hepatology, PGIMER

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

Standard Medical therapy

G-CSF

G-CSF and NAC

Arm Description

Standard medical therapy involves primary treatment with normal hospital nutrition (1800 to 2000 kcal per day). Diuretics, sodium restriction and albumin for treatment of ascites or fresh frozen plasma for coagulopathy or antibiotics for any focus of infection as spontaneous bacterial peritonitis (SBP), pneumonia, cellulitis, and urinary tract infection as indicated.

Standard Medical Therapy plus G-CSF- 5μg/Kg s.c every 12 hours for 5 consecutive days

Standard Medical Therapy plus G-CSF with intravenous NAC (day 1: NAC at 150, 50, and 100 mg/kg in 250, 500, and 1000 ml of 5% glucose solution over 30 minutes, 4 hours, and 16 hours, respectively; days 2 through 5: 100 mg/kg/day in 1000 ml of 5% glucose solution followed by oral NAC from days 6 to 28)

Outcomes

Primary Outcome Measures

Survival at the end of 90 days

Secondary Outcome Measures

Number of CD34+ cells in peripheral blood
Change in MELD score
Change in modified Maddrey's Discriminant Function at 90 days.
Modified Maddrey's Discriminant Function will be calculated using the following formula: [4.6 × (prothrombin time of patient - prothrombin time of control) + serum bilirubin in mg/dl] Modified Maddrey's Discriminant Function is a validated and well-established parameter for assessing the severity and prognosis of alcoholic hepatitis.
Change in Child Turcotte Pugh score
Number of participants with treatment-related adverse events in the different treatment groups

Full Information

First Posted
April 17, 2023
Last Updated
April 29, 2023
Sponsor
Postgraduate Institute of Medical Education and Research
search

1. Study Identification

Unique Protocol Identification Number
NCT05840640
Brief Title
Granulocyte Colony Stimulating Factor Four Week Plus N-Acetyl Cysteine in Severe Alcoholic Hepatitis
Official Title
Granulocyte Colony Stimulating Factor Four Week Plus N-Acetyl Cysteine in Severe Alcoholic Hepatitis
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
October 1, 2017 (Actual)
Primary Completion Date
February 28, 2021 (Actual)
Study Completion Date
February 28, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Postgraduate Institute of Medical Education and Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Alcoholic hepatitis is related to very high mortality rate. About 40% of the patients died within first 6 months after the detection of the clinical syndrome. Therefore, it is very essential for proper diagnosis and early treatment . In response to acute or chronic liver damage, bone marrow derived stem cells can spontaneously populate liver and differentiate into hepatic cells. Animal and human studies suggested that injured hepatocyte may be replaced by pluripotent bone marrow cells. However, this hepatocyte repopulation is highly dependent on varieties of liver injury and therapeutic conditions. The studies have suggested Granulocyte-colony stimulating factors (G-CSF) can regenerate hepatocyte by fusing with hematopoietic cells, thereby enhancing the liver histology and survival rate. G-CSF is a cytokine capable to regulate a number of functions in neutrophils. In three recent studies mobilization of bone marrow stem cells induced by G-CSF was observed in patients with alcoholic hepatitis. In two of these studies there was a survival benefit with the use of G-CSF. Alcoholism leads to decrease in endogenous antioxidant potential. Alcoholic liver disease (ALD) patients show low endogenous antioxidants. Chronic ethanol consumption cause selective deficiency in the availability of reduced glutathione (GSH) in mitochondria has been reported. This is due to impaired functioning of GSH transporter from cytosol to mitochondrial matrix. The effect on glutathione replenishing potential by N-acetyl cysteine (NAC) can be used to reduce oxidative stress, which also has excellent safety profile. Therefore, NAC can be used for severe alcoholic hepatitis treatment due to its therapeutic potential factor. NAC also inhibit apoptosis and pro-inflammatory cytokine production. In a study high doses of intravenous N-acetyl cysteine therapy for 14 days conferred neither survival benefits nor early biological improvement in severe acute alcoholic hepatitis patients with adequate nutritional support.However, these results must be viewed with caution, since the study suffered from a lack of power. In a recent study, NAC and corticosteroids combination therapy benefits among patients with severe acute alcoholic hepatitis in 1 month survival, although the final outcome at 6 month survival was not improved. There are no studies on the use of combination therapy of 4 weeks of NAC plus G-CSF in patient with severe alcoholic hepatitis. Therefore the investigators plan to study the safety and efficacy of combination therapy of G-CSF and 4 weeks of NAC in the patients with alcoholic hepatitis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholic Hepatitis
Keywords
alcoholic hepatitis, alcoholic liver disease, regeneration

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Open label randomized
Masking
None (Open Label)
Allocation
Randomized
Enrollment
66 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard Medical therapy
Arm Type
Active Comparator
Arm Description
Standard medical therapy involves primary treatment with normal hospital nutrition (1800 to 2000 kcal per day). Diuretics, sodium restriction and albumin for treatment of ascites or fresh frozen plasma for coagulopathy or antibiotics for any focus of infection as spontaneous bacterial peritonitis (SBP), pneumonia, cellulitis, and urinary tract infection as indicated.
Arm Title
G-CSF
Arm Type
Experimental
Arm Description
Standard Medical Therapy plus G-CSF- 5μg/Kg s.c every 12 hours for 5 consecutive days
Arm Title
G-CSF and NAC
Arm Type
Experimental
Arm Description
Standard Medical Therapy plus G-CSF with intravenous NAC (day 1: NAC at 150, 50, and 100 mg/kg in 250, 500, and 1000 ml of 5% glucose solution over 30 minutes, 4 hours, and 16 hours, respectively; days 2 through 5: 100 mg/kg/day in 1000 ml of 5% glucose solution followed by oral NAC from days 6 to 28)
Intervention Type
Drug
Intervention Name(s)
Standard Medical Therapy
Intervention Description
Standard medical therapy involves primary treatment with normal hospital nutrition (1800 to 2000 kcal per day). Diuretics, sodium restriction and albumin for treatment of ascites or fresh frozen plasma for coagulopathy or antibiotics for any focus of infection as spontaneous bacterial peritonitis (SBP), pneumonia, cellulitis, and urinary tract infection as indicated.
Intervention Type
Drug
Intervention Name(s)
G-CSF
Intervention Description
standard medical therapy plus G-CSF- 5μg/Kg s.c every 12 hours for 5 consecutive days
Intervention Type
Drug
Intervention Name(s)
G-CSF and NAC
Intervention Description
Standard Medical Therapy plus G-CSF with intravenous NAC (day 1: NAC at 150, 50, and 100 mg/kg in 250, 500, and 1000 ml of 5% glucose solution over 30 minutes, 4 hours, and 16 hours, respectively; days 2 through 5: 100 mg/kg/day in 1000 ml of 5% glucose solution followed by oral NAC from days 6 to 28)
Primary Outcome Measure Information:
Title
Survival at the end of 90 days
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Number of CD34+ cells in peripheral blood
Time Frame
6 days
Title
Change in MELD score
Time Frame
90 days
Title
Change in modified Maddrey's Discriminant Function at 90 days.
Description
Modified Maddrey's Discriminant Function will be calculated using the following formula: [4.6 × (prothrombin time of patient - prothrombin time of control) + serum bilirubin in mg/dl] Modified Maddrey's Discriminant Function is a validated and well-established parameter for assessing the severity and prognosis of alcoholic hepatitis.
Time Frame
90 days
Title
Change in Child Turcotte Pugh score
Time Frame
90 days
Title
Number of participants with treatment-related adverse events in the different treatment groups
Time Frame
90 days

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: • Alcoholic hepatitis patients(More than 10 years of heavy alcohol consumption (mean intake ≈ 100 g/day);Elevated aspartate aminotransferase level (but <500 IU per millilitre) and Ratio ofAST/ALT≥2 times;Elevated serum total bilirubin level ≥ 5 mgdL (86 μmol/L);Elevated INR(≥1.5) and;Neutrophilia. Patient with Maddrey's DF of≥ 32 will be included in the study, with or without biopsy) Exclusion Criteria: Age < 18 and > 75 years Hepatocellular carcinoma or portal vein thrombosis Refusal to participate in the study Serum creatinine >1.0 mg% Hepatic encephalopathy- grade 3 or 4 Upper gastrointestinal bleed in last ten days Uncontrolled bacterial infection Human immunodeficiency virus, Hepatitis B virus, Hepatitis C virus seropositivity, Autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha1-antitrypsin deficiency Pregnancy Glucocorticoid treatment Significant co-morbidity Previous known hypersensitivity to G-CSF/NAC
Facility Information:
Facility Name
Dept of Hepatology, PGIMER
City
Chandigarh
ZIP/Postal Code
160012
Country
India

12. IPD Sharing Statement

Learn more about this trial

Granulocyte Colony Stimulating Factor Four Week Plus N-Acetyl Cysteine in Severe Alcoholic Hepatitis

We'll reach out to this number within 24 hrs