Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

GCSF in Alcoholic Hepatitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03703674
Recruitment Status : Recruiting
First Posted : October 12, 2018
Last Update Posted : October 12, 2018
Sponsor:
Information provided by (Responsible Party):
Dr.Virendra Singh, Postgraduate Institute of Medical Education and Research

Brief Summary:

Alcoholic hepatitis is related to very high mortality rate. About 40% of the patients are 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 has 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 this studies there was a survival benefit with the use of G-CSF.

Therefore we plan to study the safety and efficacy of G-CSF in the patients with alcoholic hepatitis.


Condition or disease Intervention/treatment Phase
Alcoholic Hepatitis Drug: GCSF Phase 4

Detailed Description:

Detailed Description:

Patients with severe alcoholic hepatitis, admitted to Department of Hepatology PGIMER, Chandigarh will be included in the study.

METHODS

This will be an open label trial. A randomization code is generated by random number table. The patients will be randomized to receive standard medical therapy (SMT) only as control and therapy of G-CSF as case. There will be one control and one case as below:

1) SMT (control) 2) G-CSF (case): G-CSF 5 mcg/kg every 12 hourly for consecutive 5 days This will be a single time therapy. Patients will be admitted in the department of hepatology and will be assessed everyday clinically as well as by laboratory tests during therapy to assess safety and effects of treatment.

  1. Total leukocytes count will be assessed daily.
  2. Circulating CD 34 positive cells will be measured on day 0 and 6 of G-CSF therapy.
  3. In addition, ultrasonography will be performed at day 1 and 6 in order to evaluate difference in spleen size and portal vein flow.
  4. Biochemical, coagulation, and hematological parameters (Liver function tests, Renal Function Tests, Prothrombin Time, International Normalised Ratio, etc.) will be monitored periodically, daily for 1 week, then weekly for 1month and monthly for three month.

All patients will be followed at weekly interval for 1 month and then monthly for 3 months.

Outcome:

Primary Objectives:

Survival at 3 months

Secondary Objectives:

Mobilisation of CD34 positive cells in peripheral blood.Clinical/biochemical improvement in liver function profile.Improvement in prognostic scores-Maddrey's Discriminant function, MELD score, and Child score.

Safety and efficacy of G-CSF in alcoholic hepatitis


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Granulocyte Colony Stimulating Factor in Alcoholic Hepatitis
Actual Study Start Date : November 19, 2017
Estimated Primary Completion Date : November 18, 2020
Estimated Study Completion Date : November 18, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Standard Medical Therapy
Drug: standard medical therapy Standard medical therapy involves primary treatment and 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: GCSF
Granulocyte-colony stimulating factors (G-CSF)

Experimental: G-CSF + Standard Medical Therapy

Drug: standard medical therapy Standard medical therapy involves primary treatment and 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- 5 μg/Kg s.c every 12 hours for 5 consecutive days

Drug: GCSF
Granulocyte-colony stimulating factors (G-CSF)




Primary Outcome Measures :
  1. Survival at 3 months [ Time Frame: 90 DAYS ]

Secondary Outcome Measures :
  1. Mobilisation of CD34 positive cells in peripheral blood. [ Time Frame: 6 DAYS ]
  2. Improvement in MELD score [ Time Frame: 90 DAYS ]
  3. Improvement in Maddrey's Discriminant Function. [ Time Frame: 90 Days ]
  4. Improvement in Child Turcotte Pugh score. [ Time Frame: 90 Days ]
  5. Number of participants with treatment-related adverse events in the different groups. [ Time Frame: 90 Days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Alcoholic hepatitis patients:

    1. More than 10 years of heavy alcohol consumption (mean intake ≈ 100 g/day).
    2. Elevated aspartate aminotransferase level (but <500 IU per millilitre) and Ratio ofAST/ALT≥2 times
    3. Elevated serum total bilirubin level ≥ 5 mgdL (86 μmol/L)
    4. Elevated INR(≥1.5) and
    5. Neutrophilia. Patient with Maddrey's DF of ≥ 32 will be included in the study, with or without biopsy.

Exclusion Criteria:

  • 1. Age < 18 and > 75 years 2. Hepatocellular carcinoma or portal vein thrombosis 3. Refusal to participate in the study 4. Serum creatinine>1.0 mg% 5. Hepatic encephalopathy- grade 3 or 4 6. Upper gastrointestinal bleed in last ten days 7. Uncontrolled bacterial infection 8. Human immunodeficiency virus, Hepatitis B virus, Hepatitis C virus seropositivity, Autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha1-antitrypsin deficiency 9. Pregnancy 10. Glucocorticoid treatment 11. Significant co-morbidity 12. Previous known hypersensitivity to G-CSF

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03703674


Contacts
Layout table for location contacts
Contact: Virendra Singh, DM 7087009338 virendrasingh100@hotmail.com

Locations
Layout table for location information
India
Post Graduate Institute of Medical Education and Research Recruiting
Chandigarh, India, 160012
Contact: Virendra Singh    7087009338    virendrasingh100@hotmail.com   
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research

Layout table for additonal information
Responsible Party: Dr.Virendra Singh, Professor of Hepatology, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT03703674     History of Changes
Other Study ID Numbers: GCSF IN ALCOHOLIC HEPATITIS
First Posted: October 12, 2018    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatitis
Hepatitis A
Hepatitis, Alcoholic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Sargramostim
Lenograstim
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic