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

• Status: Recruiting
• Trial end date: 2021-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dayanand Medical College and Hospital
• Treatments: Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Vitamins

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