Alcoholic Hepatitis Clinical Trial
Official title:
Granulocyte Colony Stimulating Factor Four Week Plus N-Acetyl Cysteine in Severe Alcoholic Hepatitis
Verified date | April 2023 |
Source | Postgraduate Institute of Medical Education and Research |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 66 |
Est. completion date | February 28, 2021 |
Est. primary completion date | February 28, 2021 |
Accepts healthy volunteers | No |
Gender | Male |
Age group | 18 Years to 75 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
India | Dept of Hepatology, PGIMER | Chandigarh |
Lead Sponsor | Collaborator |
---|---|
Postgraduate Institute of Medical Education and Research |
India,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Survival at the end of 90 days | 90 days | ||
Secondary | Number of CD34+ cells in peripheral blood | 6 days | ||
Secondary | Change in MELD score | 90 days | ||
Secondary | 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. |
90 days | |
Secondary | Change in Child Turcotte Pugh score | 90 days | ||
Secondary | Number of participants with treatment-related adverse events in the different treatment groups | 90 days |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04066179 -
Efficacy of Monotherapy vs Combination Therapy of Corticosteroids With GCSF in Severe Alcoholic Hepatitis Patients.
|
N/A | |
Completed |
NCT03732586 -
Effect of Omega 5 Fatty Acid as an Adyuvant Treatment to Prednisone in Patients With Severe Alcoholic Hepatitis
|
N/A | |
Completed |
NCT01476995 -
Prognostic Indicators as Provided by the EPIC ClearView
|
N/A | |
Completed |
NCT00962442 -
N-Acetylcysteine in Severe Acute Alcoholic Hepatitis
|
Phase 3 | |
Not yet recruiting |
NCT06307522 -
MRG-001 in Patients With Alcoholic Hepatitis
|
Phase 2 | |
Recruiting |
NCT05018481 -
HA35 Moderate Alcoholic Hepatitis (AH) Study
|
Early Phase 1 | |
Completed |
NCT04544020 -
Changes in gUt micRobiota After Enteral Feeding (in Alcoholic Hepatitis)
|
||
Recruiting |
NCT04088370 -
Peripheral Blood Mononuclear Cells Response In Healthy Controls, Heavy Drinkers, and Patients With Alcoholic Hepatitis
|
||
Completed |
NCT04235855 -
EUS Guided Liver Biopsy - Will it Give Better Yield, More Tissue With Less Complication?
|
N/A | |
Active, not recruiting |
NCT02344680 -
Liver Fibrosis in Zambian HIV-HBV Co-infected Patients
|
||
Completed |
NCT00851981 -
Randomized, Controlled Trial of S-adenosylmethionine in Alcoholic Liver Disease
|
Phase 2 | |
Completed |
NCT04084522 -
Effect of Saturated Fat (Desi Ghee) on Gut-Liver Axis in Alcoholic Hepatitis
|
N/A | |
Recruiting |
NCT03069300 -
N-ACetylcysteine to Reduce Infection and Mortality for Alcoholic Hepatitis
|
Phase 3 | |
Terminated |
NCT02039219 -
Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH)
|
Phase 2 | |
Completed |
NCT01245257 -
Effects of Prednisolone and Pentoxifylline on the Regulation of Urea Synthesis in Alcoholic Hepatitis
|
N/A | |
Completed |
NCT02019056 -
Efficacy and Safety of MG in the Patients With Alcoholic Fatty Liver Disease and Alcoholic Hepatitis
|
Phase 2 | |
Completed |
NCT00388323 -
Adipose Tissue Involvement in Alcohol-induced Liver Inflammation in Human
|
N/A | |
Recruiting |
NCT03845205 -
Alcohol Treatment Outcomes Following Early vs. Standard Liver Transplant for SAH
|
N/A | |
Recruiting |
NCT03703674 -
GCSF in Alcoholic Hepatitis
|
Phase 4 | |
Active, not recruiting |
NCT02473341 -
Comparison of Bovine Colostrum Versus Placebo in Treatment of Severe Alcoholic Hepatitis: A Randomized Double Blind Controlled Trial
|
Phase 3 |