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Comparison of Bovine Colostrum Versus Placebo in Treatment of Severe Alcoholic Hepatitis: A Randomized Double Blind Controlled Trial (BASH)

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ClinicalTrials.gov Identifier: NCT02473341
Recruitment Status : Recruiting
First Posted : June 16, 2015
Last Update Posted : August 31, 2020
Sponsor:
Information provided by (Responsible Party):
Prof. Sandeep S Sidhu, Dayanand Medical College and Hospital

Brief Summary:

Severe Alcoholic hepatitis, defined by modified Maddrey's Discriminant Function (DF) ≥32, is associated with significant morbidity and mortality.(1,2) Of the various treatment modalities evaluated for treatment of Severe Alcoholic hepatitis, corticosteroids have been the most extensively studied.(1) Five out of 13 randomized controlled trials, and four out of 5 meta-analysis have shown a survival benefit with corticosteroids, especially in patients with DF ≥32 and/ or encephalopathy.(1-4) However, the role of corticosteroids in Severe Alcoholic hepatitis still remains controversial.(5-6) Corticosteroid therapy is not considered the ideal option by most authors because their beneficial effect seems to be confined to a highly select minority group in which the inhibitory effect of corticosteroids on liver inflammation is not outweighed by side effects such as weakened defence against infections, anti-anabolic effects, and possible ulcer promoting effects.(6) Corticosteroids are usually contraindicated in those with DF > 54 or MELD >24 (7) .Also corticosteroids are contraindicated in those with renal failure, gastro-intestinal bleed, pancreatitis and active sepsis. Therefore, there have been constant efforts to evaluate new therapies for Severe Alcoholic hepatitis (SAH). In a recent trial, combination of glucocorticoids plus N-acetylcysteine was found to improve one month survival in patients with Severe Alcoholic hepatitis, compared with glucocorticoids alone. However, the 6 month survival similar in both the groups.(8) Human colostrum and bovine colostrum are rich in protein, immunoglobulin, lactoferrin and growth factors. Recent studies suggest that colostrum components, immunoglobulin and growth factor benefits physically active person as well as in the treatment of autoimmune disorders. It is used for the treatment of a wide variety of gastrointestinal conditions, including non-steroidal anti-inflammatory drug-induced gut injury, Helicobacter pylori infection, immune deficiency related diarrhea as well as infective diarrhea.(9,10,11) It has also been sucessfully used to significantly decrease the level of Endotoxemia - lower levels of Lipopolysaccharides.

We plan to compare the efficacy of bovine colostrum versus Placebo (Pasteurized milk powder) alone in treatment of severe alcoholic hepatitis. Bovine Colostrum is rich in protein, immunoglobulin, lactoferrin and growth factors. Recent studies suggest that Colostrum components, immunoglobulin and growth factor benefits physically active person and in treatment of autoimmune disorders. It is used for the treatment of a wide variety of gastrointestinal conditions, including non-steroidal anti-inflammatory drug-induced gut injury, H pylori infection, immune deficiency related diarrhea as well as infective diarrhea.(9) The guidelines by American College of Gastroenterology (10) and other authors (11) have suggested that a combination of Corticosteroids and other drugs, which have different mechanisms of action, may be more beneficial for reducing mortality in severe alcoholic hepatitis. Hence, the investigators plan to compare the efficacy of combined therapy of Corticosteroids and Bovine colostrum versus Corticosteroids alone in treatment of severe alcoholic hepatitis.


Condition or disease Intervention/treatment Phase
Alcoholic Hepatitis Drug: Bovine Colostrum Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 174 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Comparison of Bovine Colostrum Versus Placebo in Treatment of Severe Alcoholic Hepatitis: A Randomized Double Blind Controlled Trial
Actual Study Start Date : November 14, 2017
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Bovine colostrum

Protein 1.5 gm/kg/day, energy (kcal) 30-40/day, B complex vitamins daily. Pasteurized Bovine colostrum as a freeze dried powder (20 gm thrice a day) for 4 weeks.

+ Antibiotics + Diuretics +Terlipressin for HRS + acid suppression for prophylaxis against gastrointestinal hemorrhage + EVL for variceal bleed +drugs for HE if indicated

Drug: Bovine Colostrum

Protein 1.5 gm/kg/day, energy (kcal) 30-40/day, B complex vitamins daily. Pasteurized Bovine colostrum as a freeze dried powder (20 gm thrice a day) for 4 weeks.

+ Antibiotics + Diuretics +Terlipressin for HRS + acid suppression for prophylaxis against gastrointestinal hemorrhage + EVL for variceal bleed +drugs for HE if indicated


Placebo Comparator: Placebo

Protein 1.5 gm/kg/day, energy (kcal) 30-40/day, B complex vitamins daily. Placebo (Pasteurised Milk Powder) 20 gms thrice a day for 4 weeks

+ Antibiotics + Diuretics + drugs for HE + Terlipressin for HRS + acid suppression for prophylaxis against gastrointestinal hemorrhage + EVL for variceal bleed + if indicated.

Drug: Placebo

Protein 1.5 gm/kg/day, energy (kcal) 30-40/day, B complex vitamins daily. Placebo (Pasteurised Milk Powder) 20 gms thrice a day for 4 weeks

+ Antibiotics + Diuretics + drugs for HE + Terlipressin for HRS + acid suppression for prophylaxis against gastrointestinal hemorrhage + EVL for variceal bleed + if indicated.





Primary Outcome Measures :
  1. Survival [ Time Frame: 3 month ]
    Survival at 3 month


Secondary Outcome Measures :
  1. Change in mDF levels [ Time Frame: one month ]
    Change in mDF levels will be measured at baseline and after 30 days of treatment

  2. Change in Endotoxin levels [ Time Frame: one month ]
    Change in Endotoxin levels will be measured at baseline and after 4 weeks of treatment

  3. Change in Cytokines levels [ Time Frame: one month ]
    Change in Cytokines levels will be measured at baseline and after 30 days of treatment

  4. Number of episodes of sepsis [ Time Frame: 1 month ]
    Number of episodes of sepsis (bacteremia, Pneumonia, SBP, Cellulitis, UTI)

  5. Survival [ Time Frame: 1 month ]
    Survival at 1 month



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Alcoholic hepatitis Jaundice < 3 months Bilirubin > 5 mg/dl PTI (INR) Increased: >1.4 Leucocytosis >> 11,000/micro L. AST< 300 IU/l ; AST/ALT >2
  2. Hepatic Encephalopathy
  3. Men and women age > 18 years and above
  4. DF>32
  5. MELD≥21
  6. Actively consuming alcohol within 6 weeks of entry into the study
  7. Patient with controlled upper GI bleed, resolved sepsis and acute kidney injury can be enrolled
  8. Voluntary informed consent

Exclusion Criteria

  1. Failure to obtain informed consent
  2. Jaundice more than 3 months
  3. AST>500 IU/L, ALT>300 IU/L
  4. Other concomitant causes of liver disease: viral hepatitis, autoimmune liver disease, metabolic liver disease, vascular liver disease
  5. HIV positive
  6. Cow milk allergy or severe lactose intolerance
  7. Active Gastrointestinal bleeding
  8. Acute kidney injury at time of randomization with Creatinine> 1.5 mg/dL
  9. Evidence of acute pancreatitis or biliary obstruction
  10. Subjects who are pregnant or lactating
  11. Significant systemic cardio-pulmonary illness (what if on ventilator for HE or respiratory failure) - These are terminally ill patients, hence be excluded
  12. Patients requiring the use of vasopressors or inotropic support in 12 hours prior to randomization
  13. Treatment for alcoholic hepatitis within 1 month of study entry with corticosteroids use>1 week.
  14. Any patient who has received any investigational drug or device within 30 days entering into the study.
  15. Patient who withdraw consent

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): NCT02473341


Contacts
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Contact: Sandeep Singh Sidhu, DM +919814025085 sandeepsidhu1963@gmail.com
Contact: Omesh Goyal, DM +919914821155 goyalomesh@yahoo.co.in

Locations
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India
Department of Gastroenterology, D.M.C. and Hospital Recruiting
Ludhiana, Punjab, India, 141001
Contact: Sandeep S Sidhu, DM    919814025085    dmcgastro@in.com   
Contact: Omesh Goyal, DM    919914821155    goyalomesh@yahoo.co.in   
Principal Investigator: Sandeep S Sidhu, D.M.         
Principal Investigator: Omesh Goyal, D.M.         
Sponsors and Collaborators
Dayanand Medical College and Hospital
Investigators
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Principal Investigator: Sandeep S Sidhu, DM Dayanand Medical College and Hospital, Ludhiana, Punjab, India
Principal Investigator: Dharmesh Kapoor, DM Gleneagles Global Hospital, Hyderabad
Principal Investigator: Saroj K Sinha, DM PGI Hospital, Chandigarh, India
Principal Investigator: Sandeep Nijhawan, DM SMS Hospital, Jaipur, India
Principal Investigator: Usha Dutta, DM PGI Hospital, Chandigarh, India
Publications of Results:

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Responsible Party: Prof. Sandeep S Sidhu, Prof. Sandeep Singh Sidhu, Dayanand Medical College and Hospital
ClinicalTrials.gov Identifier: NCT02473341    
Other Study ID Numbers: BASH
First Posted: June 16, 2015    Key Record Dates
Last Update Posted: August 31, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prof. Sandeep S Sidhu, Dayanand Medical College and Hospital:
Bovine Colostrum
Corticosteriods
Endotoxin
MELD
mDF
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis
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