Efficacy Of Bovine Colostrum In The Treatment Of Severe Alcohol-Associated Hepatitis: A Randomized Controlled Trial

NCT02473341 · tracked via the Priya Life Science India tracker

Sponsor

Dayanand Medical College and Hospital

Phase

Phase 3

Started

2017-11-14

Last updated

2026-07-21

Condition(s) studied

Alcoholic Hepatitis

Investigational drug(s) / intervention(s)

Bovine ColostrumPlacebo

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: 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.

Study summary

Severe alcohol-associated hepatitis (sAH)is associated with hepatocellular necrosis, inflammation, hyperactivated immune system, paradoxical immune exhaustion, leaky gut, and alteration in the gut microbiome. The leading cause of mortality is a bacterial infection with multi-organ failure.

Pentoxifylline was ineffective and Interleukin-1-based therapies - Anakinra and Canakinumab have not improved survival rates. The granulocyte colony-stimulating factor has shown mixed results. Indian studies improved 90-day survival, while Western studies on Pegfilgrastim have been negative. Corticosteroids decrease the mortality for only a month. In a recent study on Severe alcohol-associated hepatitis, Larsucosterol, a DNA methyltransferase inhibitor, was associated with non-significant improvement in 90-day mortality: 14.7 % (30 mg/day) and 16.67 % (90 mg/day) versus 24.27% on Methylprednisolone. Thus, a more durable treatment of severe alcohol-associated hepatitis is needed.

Bovine Colostrum contains many bioactive components such as immunoglobulin G, A, and M (70 - 80 % of total protein), Lactoferrin and Short-chain fatty acids. Bovine Colostrum has 30-100 times higher Lactoferrin concentration than milk. IgG and Lactoferrin synergistically neutralise lipopolysaccharide/ Endotoxin and act on mucosa-associated lymphoid tissue of the leaky gut, transforming it into healthy mucosa.

Fewer bacteria and Endotoxins - Pathogen-associated molecular patterns enter the portal circulation to interact with Toll-Like Receptor - 4 of the Liver Kupffer cells. Proinflammatory cytokines such as interleukins-1,6,8 and tumour necrosis factor-alpha, generation decreases, mitigating hepatocyte inflammation, necrosis, and cell death. We therefore conducted a multicenter, phase 3, double-blind, randomized, placebo-controlled trial to determine whether Bovine Colostrum, in addition to standard medical therapy, improves 90-day survival among patients with sAH. Secondary objectives were to assess its effects on liver disease severity, endotoxemia, systemic inflammatory markers, sepsis, and safety.

Eligibility

Sex

ALL

Min age

18 Years

Max age

75 Years

Healthy volunteers

Inclusion Criteria: * Onset of jaundice within prior 8 weeks * Ongoing consumption of \> 40 (female) or 60 (males) g alcohol/day for 6 months or more, with less than 60 days of abstinence before the onset of jaundice * Aspartate aminotransferase \> 50, aspartate aminotransferase/alanine aminotransferase \> 1.5, and both values \< 400 IU/L * Serum bilirubin (total) \> 3.0 mg/dL * Liver biopsy confirmation in patients with confounding factors including possible ischemic hepatitis (eg, severe upper gastrointestinal bleed, hypotension, or cocaine use within 7 days); possible DILI; uncertain alcohol use assessment (eg, patient denies excessive alcohol use); and atypical laboratory tests (eg, AST \< 50 IU/mL or \> 400 IU/mL, AST/ALT ratio \< 1.5), antinuclear antibody \> 1:160 or SMA \> 1:80 * Maddrey's discriminant function ≥ 32 assuming a control prothrombin time of 12 seconds * Model for End-stage Liver Disease score \> 20 Exclusion Criteria * Uncontrolled infections * Multiorgan failure * Uncontrolled upper gastrointestinal bleeding. "However, patients with recent Upper Gastro Intestinal bleeding, without significant hypotension that is controlled for \>48 hours, will be included in the study." * Preexisting kidney injury with serum creatinine \> 2.5 mg/dL * Other underlying liver diseases including hepatitis B infection,\* autoimmune liver diseases, Wilson disease, suspected drug-induced liver injury\* * Hepatocellular carcinoma or other active malignancies except skin cancer * Pregnancy * Uncontrolled drug addiction * Cow milk allergy or severe lactose intol

Primary outcome measure(s)

Survival — 3 month
Survival at 3 month

Trial sites (5)

Facility	City	Region
Department of Gastroenterology, Dayanand Medical College and Hospital	Ludhiana	Punjab
Post Graduate Medical Institute of Medical Education and Research	Chandigarh	India
Department of Hepatology, Global Hospital	Hyderabad	India
Sawai Man Singh Medical College	Jaipur	India
All India Institute of Medical Sciences	New Delhi	India

Other trials for the same condition

Randomized Controlled Trial of Mycophenolate Mofetil Versus Steroid Therapy in Alcoholic Hepatitis Starting soon

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

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