Efficacy of Combination Therapy of Glucocorticoids and Bovine Colostrum in Treatment of Severe Alcoholic Hepatitis.

NCT02265328 | Completed Phase 2 DMC

• 1 other identifier: COBS-2014
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Severe Alcoholic hepatitis (SAH), defined by modified Maddrey's Discriminant Function (DF) ≥32, is associated with significant morbidity and mortality. Of the various treatment modalities evaluated for treatment of SAH, corticosteroids have been the most extensively studied. Five out of 13 RCTs, and four out of 5 meta-analysis have shown a survival benefit with corticosteroids, especially in patients with DF ≥32 and/ or encephalopathy.However, the role of corticosteroids in SAH still remains somewhat controversial. Corticosteroid therapy is not considered the ideal option by all authors because their beneficial effect seems to be confined to a highly selected 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. Also corticosteroids are contraindicated in patients with renal failure, gastro-intestinal (GI) bleed, pancreatitis and active sepsis. Therefore, there have been constant efforts to evaluate new therapies for SAH. In a recent trial, combination of glucocorticoids plus N-acetylcysteine was found to improve one month survival in patients with SAH, compared with glucocorticoids alone. However the 6 month survival was not different in both groups. Human Colostrum (HC) and Bovine Colostrum (BC) are rich in protein, immunoglobulin, lactoferrin and growth factors. Recent studies suggest that colostrum components, Lactroferrin, 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. The guidelines by American College of Gastroenterology and other authors have suggested that a combination of CS and other drugs, which have different mechanisms of action, may be more beneficial for reducing mortality in SAH. Hence, we plan to conduct this pilot study to investigate the efficacy of a novel combination of corticosteroids, and Bovine colostrum in the treatment of SAH.

Conditions

Severe Alcoholic Hepatitis in 'Extremis'- Defined by mDF>54

Keywords

Severe Alcoholic Hepatitis in 'Extremis'; Bovine Colostrum; Glucocorticoids

Outcome Measures

Primary Outcomes (1)

• Change in mDf Value from baseline to 8 weeks

  2 month

Secondary Outcomes (2)

• Change in Endotoxin level from baseline to 8 weeks

  2 month

• Cytokines Levels (αTNF, IL 6, IL 8) from baseline to 8 weeks.

  2 month

Study Arms (1)

Bovine colostrum + prednisolone

EXPERIMENTAL

1. Enteral nutrition: Protein 1.5 gm/kg/day, energy (kcal) 40/kg/day, carbohydrate 67-80%, Fat 20-33%. 2. Oral prednisolone 40mg/day × 4 weeks and tapered to \<40mg/day for next 4 weeks. If Lilli score \> 0.45 after 7 days, then GC would be stopped and patients will be counselled for liver transplantation. 3. Oral Bovine colostrum (200 ml (20 gram) TDS × 2 months.

Dietary Supplement: Bovine colostrum; Dietary Supplement: Enteral Nutrition; Other: prednisolone

Interventions

Bovine colostrum DIETARY_SUPPLEMENT

Oral Bovine colostrum 200 ml (20 gram) TDS × 2 months

Bovine colostrum + prednisolone

Enteral Nutrition DIETARY_SUPPLEMENT

Enteral nutrition: Protein 1.5 gm/kg/day, energy (kcal) 40/kg/day, carbohydrate 67-80%, Fat 20-33%.

Bovine colostrum + prednisolone

prednisolone OTHER

Oral prednisolone 40mg/day × 4 weeks and tapered to \<40mg/day for next 4 weeks. (If Lilli score \> 0.45 after 7 days, then prednisolone would be stopped)

Also known as: Wysolone, Predicort

Bovine colostrum + prednisolone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Severe Alcoholic hepatitis (mDF \> 54)
• Age 18-65 Year
• \. Actively consuming alcohol within 6 weeks of entry into the study

You may not qualify if:

• Failure to obtain informed consent
• Active infection or sepsis
• Other concomitant causes of liver disease: viral hepatitis, autoimmune liver disease, metabolic liver disease, vascular liver disease
• HIV positive
• Cow milk allergy or severe lactose intolerance
• Active Gastrointestinal bleeding
• Acute kidney injury at time of randomization with Creatinine \> 1.5 mg/dL
• Evidence of acute pancreatitis or biliary obstruction
• Subjects who are pregnant or lactating
• Significant systemic cardio-pulmonary illness
• Patients requiring the use of vasopressors or inotropic support in 12 hours prior to randomization
• Treatment for alcoholic hepatitis within 1 month of study entry with corticosteroids use\>1 week.
• Any patient who has received any investigational drug or device within 30 days entering into the study

Sponsors & Collaborators

• Dayanand Medical College and Hospital: lead

Study Sites (1)

Dyanand Medical College and Hospital

Ludhiana, Punjab, 141001, India

Location

MeSH Terms

Interventions

Enteral Nutrition; Prednisolone

Intervention Hierarchy (Ancestors)

Feeding Methods; Therapeutics; Nutritional Support; Nutrition Therapy; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Sandeep S Sidhu, MD,DM

  Dayanand Medical College and Hospital

  PRINCIPAL INVESTIGATOR

• Omesh Goyal, MD,DM

  Dayanand Medical College and Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Sandeep S sidhu

Study Record Dates

• First Submitted: September 8, 2014
• First Posted: October 15, 2014
• Study Start: September 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: June 1, 2015
• Last Updated: September 15, 2015

Record last verified: 2015-09

Locations

IN (1)