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Effect of Saturated Fat (Desi Ghee) on Gut-Liver Axis in Alcoholic Hepatitis (SFAH)

Primary Purpose

Alcoholic Hepatitis

Status
Completed
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Saturated Fat- Desi Ghee (Clarified Butter)
Soyabean Oil
Sponsored by
Institute of Liver and Biliary Sciences, India
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcoholic Hepatitis focused on measuring Alcoholic Hepatitis, Gut Microbiota, Dysbiosis, Malnutrition, Saturated Fat

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

All patients with Severe Alcoholic Hepatitis

  • Aged between 18-60 years
  • Having Maddrey Score of >32
  • Last Intake of alcohol from 1 day to 60days
  • Patients who agree for complete alcohol abstinence from the day of enrollment

Exclusion Criteria:

Patients with-

  • Maddrey Score of <32 and >100
  • Comorbidities- Diabetes, Hypertension, Coronary Artery Disease, Chronic Kidney Disease, Hypothyroid
  • Continuing Alcohol intake- Non-compliant patients
  • Constipation
  • On Laxatives until 1 month prior to study
  • On probiotics until 1 month prior to study

Sites / Locations

  • Institute of Liver and Biliary Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Standard Treatment Group

Intervention Arm

Arm Description

In addition to standard pharmacological treatment, this group would receive a diet comprising of 35-40 kcal. The total distribution of the calories would be as 55-60% from carbohydrates, 20% from protein and 30% from fat, a fixed amount of 50g of oil would be given and the remaining amount of fat would be met by the invisible dietary fat. The source of visible dietary fat would be refined soyabean oil. This group would not receive any fat in the form of Desi ghee or butter or any nutritional supplement other than the prescribed diet. The diet would be explained to the patient by individual diet charts.

In addition to standard pharmacological treatment, this group would receive a diet comprising of 35-40kcal and 1.2-1.5gm protein per kg ideal body weight per day. The total distribution of the calories would be as 55-60% from carbohydrates, 20% from protein and 30-35% from fat, a fixed amount of 50g of ghee would be given in 3 divided doses of 30 ml to be taken raw, 20 ml to be used for cooking and the remaining amount of fat would be met by the invisible dietary fat. The source of visible fat would be exclusively Desi ghee. This group would not receive any fat in the form of butter or any other oil or any other nutritional supplement other than the prescribed diet. The diet would be explained to the patient by individual diet charts.

Outcomes

Primary Outcome Measures

To determine the improvement in cirrhosis dysbiosis ratio (CDR) associated with saturated fat in patients with severe alcoholic hepatitis.
The stool sample of the patients would be processed by 16s ribosomal RNA Gene sequencing to observe the diversity, abundance an evenness of the microbial community and thereafter Cirrhosis dysbiosis ratio (CDR) would be calculated at the starting and the end of the study i.e at baseline and at the end of two months.

Secondary Outcome Measures

To study the serum endotoxin (lipoploysacchride) levels in patients with severe alcoholic hepatitis
The collected blood sample would be assessed for endotoxin levels by using Toxin Sensor TM Chromogenic LAL Endotoxin Assay Kit

Full Information

First Posted
August 31, 2019
Last Updated
March 29, 2022
Sponsor
Institute of Liver and Biliary Sciences, India
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1. Study Identification

Unique Protocol Identification Number
NCT04084522
Brief Title
Effect of Saturated Fat (Desi Ghee) on Gut-Liver Axis in Alcoholic Hepatitis
Acronym
SFAH
Official Title
Effect of Saturated Fat (Desi Ghee) on Gut-Liver Axis in Alcoholic Hepatitis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
October 1, 2019 (Actual)
Primary Completion Date
January 31, 2022 (Actual)
Study Completion Date
January 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Liver and Biliary Sciences, India

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The pathogenesis of the alcoholic liver disease (ALD) is a complex interplay of various etiopathological factors other than direct alcohol toxicity. These factors include inflammation & oxidative stress, dysbiosis, intestinal hyperpermeability, and endotoxemia. Dietary fats not only improve nutritional status in ALD but specific properties of saturated fats (SF) have the potential to favourably modulate these causative factors. This project has two parts, in the animal study 10 groups of murine model of alcoholic hepatitis (AH) would be given SF in the form of Desi Ghee and in the human study patients with AH would be randomized into two groups, one with SF ( Desi Ghee) and the other with usual unsaturated fat (cooking oil). In all effect of SF on gut microbiota, hepatic steatosis, TLR-4 expression, serum adiponectin, endotoxin levels, intestinal tight junction proteins and inflammatory markers in murine models of AH, along with hepatic morbidity & lipid profile, in patients with ALD would be studied.
Detailed Description
Alcohol is one of the predominant causes of liver diseases and liver-related deaths worldwide. 10% of heavy drinkers consuming more than 30g /day of alcohol for 5 years develop alcoholic liver disease (ALD). The liver acts as a major organ in alcohol metabolism. Alcohol is metabolized to acetaldehyde, the key toxin in alcohol mediated liver injury which gets converted to reactive oxygen species (ROS) through oxidative pathway thus leading to hepatocyte injury. Several experimental and human studies have shown that alcohol also causes intestinal bacterial overgrowth, intestinal mucosal damage and enhances intestinal permeability, leading to translocation of bacteria and their by-products (like LPS) in the portal circulation. Bacteria further stimulate the production of ROS and pro-inflammatory cytokines like TNF-alpha, IL-6, & chemokines, thus further damaging the liver. Alcohol intake not only causes bacterial overgrowth but also brings a qualitative change in the type of bacteria. The number of gram-negative bacteria like Enterobacteriaceae / Proteobacteria - E.Coli, Firmicutes -Enterococcocus, Bacteriodetes- Fusobacteria and Staphylococaceae -Staphylococcus increase whereas the number of gram-positive bacteria viz. Firmicutes -Lactobacillus, Ruminococcaceae, Lachnospiraceae; Actinobacteria -Bifidobacterium decrease. This change is termed dysbiosis. Thus alcohol-related liver injury is potentiated by alcohol-induced gut barrier dysfunction and ensuing cascade of events, involving dysbiosis. Studies suggest that probiotic administration decreased alcohol-induced dysbiosis, TNF- alpha & IL-6 levels, and improves gut leakiness & liver inflammation. Probiotics also restore the level of lactobacilli thus creating more acidic environment, lowering the intestinal pH & stabilizing mucosal barrier, thereby preventing microbial translocation & blocking TLR-4 signaling cascade and attenuating liver injury. Hence there is evidence that suggests to targeting dysbiosis improves alcohol-related liver disease. Studies have also shown that lactobacilli use saturated fat (SF) for its growth and supplementing SF improves gut lactobacilli levels and subsequently decreases the progression of ALD. Low levels of microbial long-chain saturated fat caused due to alcohol compromise the growth of lactobacillus and hence disrupt gut barrier integrity. A large multicentre epidemiologic study in chronic alcoholics with comparable per capita alcohol intake has shown that intake of saturated fat is associated with lower mortality rates as compared to unsaturated fats (USF) Diet rich in SF has been found to prevent ethanol-induced changes viz. an increase in proteobacteria & liver steatosis, which were actually increased with the consumption of USF. Yet another study reported that the SF diet improved intestinal tight junction expression and alleviated intestinal inflammation caused due to ethanol intake. Supplementation of long-chain fatty SF to ethanol injured mice with increased intestinal permeability restored metabolic homeostasis with decreased intestinal bad bacteria levels where supposedly saturated fat serves as a vitamin B substitute and promotes the growth of lactobacilli species which ameliorates alcoholic liver injury. Alcohol induced disruption in the intestinal tight junction protein levels, endotoxemia and hepatic LPS signaling were found to be alleviated by SF in the form of medium chain triglycerides. Dietary SF (e.g., palm oil or MCT oil) reversed the established experimental ALD in rats, and improved liver histological changes despite continued intragastric ethanol administration. Hence the supplementation of SF in ALD is a logical manoeuvre within the nutritional therapy of this disease, as almost 90% of these patients are malnourished primarily due to a reduced diet intake. Fats are concentrated source of energy which makes the food palatable, hence making the attainment of higher calorie (35-40 kcal/kg body weight/day) target possible. With this background use of SF in ALD is a promising modality in the medical armamentarium, given the fact that nutrition remains the cornerstone of the overall therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholic Hepatitis
Keywords
Alcoholic Hepatitis, Gut Microbiota, Dysbiosis, Malnutrition, Saturated Fat

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
As it is a nutritional intervention masking of the either of participants or investigator or other investigator is not possible
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard Treatment Group
Arm Type
Placebo Comparator
Arm Description
In addition to standard pharmacological treatment, this group would receive a diet comprising of 35-40 kcal. The total distribution of the calories would be as 55-60% from carbohydrates, 20% from protein and 30% from fat, a fixed amount of 50g of oil would be given and the remaining amount of fat would be met by the invisible dietary fat. The source of visible dietary fat would be refined soyabean oil. This group would not receive any fat in the form of Desi ghee or butter or any nutritional supplement other than the prescribed diet. The diet would be explained to the patient by individual diet charts.
Arm Title
Intervention Arm
Arm Type
Active Comparator
Arm Description
In addition to standard pharmacological treatment, this group would receive a diet comprising of 35-40kcal and 1.2-1.5gm protein per kg ideal body weight per day. The total distribution of the calories would be as 55-60% from carbohydrates, 20% from protein and 30-35% from fat, a fixed amount of 50g of ghee would be given in 3 divided doses of 30 ml to be taken raw, 20 ml to be used for cooking and the remaining amount of fat would be met by the invisible dietary fat. The source of visible fat would be exclusively Desi ghee. This group would not receive any fat in the form of butter or any other oil or any other nutritional supplement other than the prescribed diet. The diet would be explained to the patient by individual diet charts.
Intervention Type
Dietary Supplement
Intervention Name(s)
Saturated Fat- Desi Ghee (Clarified Butter)
Intervention Description
Desi Ghee which is also known as clarified butter contains around 70% of saturated fat. in India it is one of the important culinary items which promotes longevity and protects against various diseases, attributing numerous health benefits. Ghee consumption has also significant hypolipidemic and hypocholesterolemic effects.
Intervention Type
Dietary Supplement
Intervention Name(s)
Soyabean Oil
Intervention Description
Soyabean Oil consists of around 84% of unsaturated fat and is the most widely used source of unsaturated fat used in the area.
Primary Outcome Measure Information:
Title
To determine the improvement in cirrhosis dysbiosis ratio (CDR) associated with saturated fat in patients with severe alcoholic hepatitis.
Description
The stool sample of the patients would be processed by 16s ribosomal RNA Gene sequencing to observe the diversity, abundance an evenness of the microbial community and thereafter Cirrhosis dysbiosis ratio (CDR) would be calculated at the starting and the end of the study i.e at baseline and at the end of two months.
Time Frame
2 months
Secondary Outcome Measure Information:
Title
To study the serum endotoxin (lipoploysacchride) levels in patients with severe alcoholic hepatitis
Description
The collected blood sample would be assessed for endotoxin levels by using Toxin Sensor TM Chromogenic LAL Endotoxin Assay Kit
Time Frame
2 months
Other Pre-specified Outcome Measures:
Title
To study the serum pro- inflammatory marker, TNF-alpha in patients with severe alcoholic hepatitis
Description
The collected blood sample would be assessed for TNF- alpha levels by using Quantikine ELISA kit
Time Frame
2 months
Title
To study the serum pro- inflammatory marker, IL-6 in patients with severe alcoholic hepatitis
Description
The collected blood sample would be assessed for IL-6 levels by using Quantikine ELISA kit
Time Frame
2 months
Title
To study the serum pro- inflammatory marker, NF-kB in patients with severe alcoholic hepatitis
Description
The collected blood sample would be assessed for NF-kB levels by using Quantikine ELISA kit
Time Frame
2 months
Title
To study the serum anti- inflammatory marker,adiponectin in patients with severe alcoholic hepatitis
Description
The collected blood sample would be assessed for adiponectin levels by using Quantikine ELISA kit
Time Frame
2 months
Title
To study the serum anti- inflammatory marker, IL-10 in patients with severe alcoholic hepatitis
Description
The collected blood sample would be assessed for IL-10 levels by using Quantikine ELISA kit
Time Frame
2 months
Title
To observe the expression of gut microbiome specific genes in patients with severe alcoholic hepatitis
Description
The stool sample collected would be assessed for Fab genes (G and F) expression using 16s ribosomal gene sequencing.
Time Frame
2 months
Title
To observe Clinical benefit in patients of severe alcoholic hepatitis
Description
Clinical benefit in terms of resolution of signs & symptoms to be observed.
Time Frame
2 months
Title
To observe Clinical benefit in patients of severe alcoholic hepatitis
Description
Clinical benefit in terms of improvement in Bilirubin levels to be observed
Time Frame
2 months
Title
To observe Clinical benefit in patients of severe alcoholic hepatitis
Description
Clinical benefit in terms of reduction of AST & ALT levels to be observed
Time Frame
2 months
Title
To observe Clinical benefit in patients of severe alcoholic hepatitis
Description
Clinical benefit in terms of reduction Maddrey Score to be observed
Time Frame
2 months
Title
To observe the Nutritional status in patients with Severe Alcoholic hepatitis
Description
Body composition analysis by BIA (Bioelectrical impedance analysis) for nutritional screening of the patients
Time Frame
2 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All patients with Severe Alcoholic Hepatitis Aged between 18-60 years Having Maddrey Score of >32 Last Intake of alcohol from 1 day to 60days Patients who agree for complete alcohol abstinence from the day of enrollment Exclusion Criteria: Patients with- Maddrey Score of <32 and >100 Comorbidities- Diabetes, Hypertension, Coronary Artery Disease, Chronic Kidney Disease, Hypothyroid Continuing Alcohol intake- Non-compliant patients Constipation On Laxatives until 1 month prior to study On probiotics until 1 month prior to study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr. Jaya Benjamin, PhD
Organizational Affiliation
Associate Professor
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Liver and Biliary Sciences
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110070
Country
India

12. IPD Sharing Statement

Plan to Share IPD
No
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17718394
Citation
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Results Reference
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19645728
Citation
Mutlu E, Keshavarzian A, Engen P, Forsyth CB, Sikaroodi M, Gillevet P. Intestinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats. Alcohol Clin Exp Res. 2009 Oct;33(10):1836-46. doi: 10.1111/j.1530-0277.2009.01022.x. Epub 2009 Jul 23.
Results Reference
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Links:
URL
https://www.ncbi.nlm.nih.gov/pubmed/
Description
Pubmed has been used for all the papers search.

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Effect of Saturated Fat (Desi Ghee) on Gut-Liver Axis in Alcoholic Hepatitis

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