Alcoholic HepatitisPhase 4NCT05840640
Granulocyte Colony Stimulating Factor Four Week Plus N-Acetyl Cysteine in Severe Alcoholic Hepatitis
A Phase 4 study testing Standard Medical Therapy, G-CSF and G-CSF and NAC in people with Alcoholic Hepatitis, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial 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 . Read more about this study
- Who is it for?
- Ages 18 to 75 years, men only
- Conditions the study is for
- Alcoholic Hepatitis
- What is being tested?
- Standard Medical Therapy, G-CSF and G-CSF and NAC
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteIndia
- Study dates
- 1 Oct 2017to 28 Feb 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
- Conditions
- Alcoholic Hepatitis
- Being tested
- Standard Medical Therapy, G-CSF, G-CSF and NAC
- Keywords
- alcoholic hepatitis, alcoholic liver disease, regeneration
- Medical subject headings
- Hepatitis, Alcoholic, Liver Diseases, Alcoholic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard Medical TherapyDrug
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.
G-CSFDrug
standard medical therapy plus G-CSF- 5μg/Kg s.c every 12 hours for 5 consecutive days
G-CSF and NACDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| Standard Medical therapy | Active comparator | 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. Receives: Drug: Standard Medical Therapy |
| G-CSF | Experimental | Standard Medical Therapy plus G-CSF- 5μg/Kg s.c every 12 hours for 5 consecutive days Receives: Drug: Standard Medical Therapy; Drug: G-CSF |
| G-CSF and NAC | Experimental | 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) Receives: Drug: Standard Medical Therapy; Drug: G-CSF; Drug: G-CSF and NAC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival at the end of 90 days
Measured: 90 days
Secondary outcomes (5)
Number of CD34+ cells in peripheral blood
Measured: 6 days
Change in MELD score
Measured: 90 days
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.
Measured: 90 days
Change in Child Turcotte Pugh score
Measured: 90 days
Number of participants with treatment-related adverse events in the different treatment groups
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2023
- Study start1 Oct 2017
- Primary completion28 Feb 2021
- Study completion28 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcoholic HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Open label randomized
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr.Virendra Singh, Post Graduate Institute of Medical Education and Research, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05840640
- Sponsor's protocol ID
- GCSF IN SAH
- Status last verified
- Apr 2023
- First submitted
- 17 Apr 2023
- Last updated
- 3 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Granulocyte Colony Stimulating Factor Four Week Plus N-Acetyl Cysteine in Severe Alcoholic Hepatitis
- ClinicalTrials.gov ID
- NCT05840640
- Acronym / sponsor ID
- GCSF IN SAH
- Conditions
- Alcoholic Hepatitis
- Keywords
- alcoholic hepatitis, alcoholic liver disease, regeneration
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 28 Feb 2021 (actual)
- Study completion
- 28 Feb 2021 (actual)
- First posted
- 3 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Open label randomized
| Arm | Type | Receives |
|---|---|---|
| Standard Medical therapy | Active comparator | Drug: Standard Medical TherapyStandard 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. |
| G-CSF | Experimental | Drug: Standard Medical Therapy, Drug: G-CSFStandard Medical Therapy plus G-CSF- 5μg/Kg s.c every 12 hours for 5 consecutive days |
| G-CSF and NAC | Experimental | Drug: Standard Medical Therapy, Drug: G-CSF, Drug: G-CSF and NACStandard 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) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard Medical TherapyStandard 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. | Drug | G-CSF, G-CSF and NAC, Standard Medical therapy |
| G-CSFstandard medical therapy plus G-CSF- 5μg/Kg s.c every 12 hours for 5 consecutive days | Drug | G-CSF, G-CSF and NAC |
| G-CSF and NACStandard 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) | Drug | G-CSF and NAC |
Primary outcome
Survival at the end of 90 days
Time frame: 90 days
5 secondary outcomes
Number of CD34+ cells in peripheral blood
Time frame: 6 days
Change in MELD score
Time frame: 90 days
Change in modified Maddrey's Discriminant Function at 90 days.
Time frame: 90 days
Change in Child Turcotte Pugh score
Time frame: 90 days
Number of participants with treatment-related adverse events in the different treatment groups
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Standard Medical Therapy, G-CSF and G-CSF and NAC in people with Alcoholic Hepatitis, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival at the end of 90 days (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2023.