NCT04084522

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Oct 2019

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 31, 2019

Completed
10 days until next milestone

First Posted

Study publicly available on registry

September 10, 2019

Completed
21 days until next milestone

Study Start

First participant enrolled

October 1, 2019

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2022

Completed
Last Updated

March 31, 2022

Status Verified

February 1, 2022

Enrollment Period

2.3 years

First QC Date

August 31, 2019

Last Update Submit

March 29, 2022

Conditions

Alcoholic Hepatitis

Keywords

Alcoholic HepatitisGut MicrobiotaDysbiosisMalnutritionSaturated Fat

Outcome Measures

Primary Outcomes (1)

  • 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.

    2 months

Secondary Outcomes (1)

  • To study the serum endotoxin (lipoploysacchride) levels in patients with severe alcoholic hepatitis

    2 months

Other Outcomes (11)

  • To study the serum pro- inflammatory marker, TNF-alpha in patients with severe alcoholic hepatitis

    2 months

  • To study the serum pro- inflammatory marker, IL-6 in patients with severe alcoholic hepatitis

    2 months

  • To study the serum pro- inflammatory marker, NF-kB in patients with severe alcoholic hepatitis

    2 months

  • +8 more other outcomes

Study Arms (2)

Standard Treatment Group

PLACEBO COMPARATOR

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.

Dietary Supplement: Soyabean Oil

Intervention Arm

ACTIVE COMPARATOR

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.

Dietary Supplement: Saturated Fat- Desi Ghee (Clarified Butter)

Interventions

Saturated Fat- Desi Ghee (Clarified Butter)DIETARY_SUPPLEMENT

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 Arm
Soyabean OilDIETARY_SUPPLEMENT

Soyabean Oil consists of around 84% of unsaturated fat and is the most widely used source of unsaturated fat used in the area.

Standard Treatment Group

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Institute of Liver and Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location

Related Publications (11)

  • Edenberg HJ. The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Res Health. 2007;30(1):5-13.

    PMID: 17718394BACKGROUND

  • Keshavarzian A, Farhadi A, Forsyth CB, Rangan J, Jakate S, Shaikh M, Banan A, Fields JZ. Evidence that chronic alcohol exposure promotes intestinal oxidative stress, intestinal hyperpermeability and endotoxemia prior to development of alcoholic steatohepatitis in rats. J Hepatol. 2009 Mar;50(3):538-47. doi: 10.1016/j.jhep.2008.10.028. Epub 2008 Dec 29.

    PMID: 19155080BACKGROUND

  • 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.

    PMID: 19645728BACKGROUND

  • Su GL, Rahemtulla A, Thomas P, Klein RD, Wang SC, Nanji AA. CD14 and lipopolysaccharide binding protein expression in a rat model of alcoholic liver disease. Am J Pathol. 1998 Mar;152(3):841-9.

    PMID: 9502426BACKGROUND

  • Hritz I, Mandrekar P, Velayudham A, Catalano D, Dolganiuc A, Kodys K, Kurt-Jones E, Szabo G. The critical role of toll-like receptor (TLR) 4 in alcoholic liver disease is independent of the common TLR adapter MyD88. Hepatology. 2008 Oct;48(4):1224-31. doi: 10.1002/hep.22470.

    PMID: 18792393BACKGROUND

  • Nanji AA, Jokelainen K, Tipoe GL, Rahemtulla A, Dannenberg AJ. Dietary saturated fatty acids reverse inflammatory and fibrotic changes in rat liver despite continued ethanol administration. J Pharmacol Exp Ther. 2001 Nov;299(2):638-44.

    PMID: 11602676BACKGROUND

  • Kirpich IA, Petrosino J, Ajami N, Feng W, Wang Y, Liu Y, Beier JI, Barve SS, Yin X, Wei X, Zhang X, McClain CJ. Saturated and Unsaturated Dietary Fats Differentially Modulate Ethanol-Induced Changes in Gut Microbiome and Metabolome in a Mouse Model of Alcoholic Liver Disease. Am J Pathol. 2016 Apr;186(4):765-76. doi: 10.1016/j.ajpath.2015.11.017.

    PMID: 27012191BACKGROUND

  • Kirpich IA, Solovieva NV, Leikhter SN, Shidakova NA, Lebedeva OV, Sidorov PI, Bazhukova TA, Soloviev AG, Barve SS, McClain CJ, Cave M. Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury: a pilot study. Alcohol. 2008 Dec;42(8):675-82. doi: 10.1016/j.alcohol.2008.08.006.

    PMID: 19038698BACKGROUND

  • Chen P, Torralba M, Tan J, Embree M, Zengler K, Starkel P, van Pijkeren JP, DePew J, Loomba R, Ho SB, Bajaj JS, Mutlu EA, Keshavarzian A, Tsukamoto H, Nelson KE, Fouts DE, Schnabl B. Supplementation of saturated long-chain fatty acids maintains intestinal eubiosis and reduces ethanol-induced liver injury in mice. Gastroenterology. 2015 Jan;148(1):203-214.e16. doi: 10.1053/j.gastro.2014.09.014. Epub 2014 Sep 16.

    PMID: 25239591BACKGROUND

  • Kirpich IA, Feng W, Wang Y, Liu Y, Barker DF, Barve SS, McClain CJ. The type of dietary fat modulates intestinal tight junction integrity, gut permeability, and hepatic toll-like receptor expression in a mouse model of alcoholic liver disease. Alcohol Clin Exp Res. 2012 May;36(5):835-46. doi: 10.1111/j.1530-0277.2011.01673.x. Epub 2011 Dec 7.

    PMID: 22150547BACKGROUND

  • Zhong W, Li Q, Xie G, Sun X, Tan X, Sun X, Jia W, Zhou Z. Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats. Am J Physiol Gastrointest Liver Physiol. 2013 Dec;305(12):G919-32. doi: 10.1152/ajpgi.00226.2013. Epub 2013 Oct 10.

    PMID: 24113767BACKGROUND

Related Links

MeSH Terms

Conditions

Hepatitis, AlcoholicDysbiosisMalnutrition

Interventions

Ghee

Condition Hierarchy (Ancestors)

HepatitisLiver DiseasesDigestive System DiseasesLiver Diseases, AlcoholicAlcohol-Induced DisordersAlcohol-Related DisordersSubstance-Related DisordersChemically-Induced DisordersPathologic ProcessesPathological Conditions, Signs and SymptomsNutrition DisordersNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

ButterDietary FatsFatsLipidsDairy ProductsFoodDiet, Food, and NutritionPhysiological PhenomenaFood and Beverages

Study Officials

  • Dr. Jaya Benjamin, PhD

    Associate Professor

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Masking Details
As it is a nutritional intervention masking of the either of participants or investigator or other investigator is not possible
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 31, 2019

First Posted

September 10, 2019

Study Start

October 1, 2019

Primary Completion

January 31, 2022

Study Completion

January 31, 2022

Last Updated

March 31, 2022

Record last verified: 2022-02

Data Sharing

IPD Sharing
Will not share

Locations

IN(1)