Efficacy and Safety of a Probiotic Composition as Adjunct in MAFL Management

Efficacy and Safety of a Probiotic Composition as Adjunct Treatment in the Comprehensive Management of Metabolism-Associated Hepatic Steatosis in Adults

Some studies have shown beneficial results with probiotics on hepatic function of subjects with fatty liver, but significant variability has been noted among probiotic formulations. This study aims at providing a comprehensive characterization of the effect of a particular probiotic formula in hepatic function of said subjects.

Study Overview

• Status: Completed
• Conditions: Non Alcoholic Fatty Liver
• Intervention / Treatment: Dietary supplement: Probiotic composition; Other: Placebo

Detailed Description

Some studies have shown beneficial results with probiotics on hepatic function of subjects with Non-Alcoholic Fatty Liver (NAFL) also known as Metabolism-Associated Fatty Liver (MAFL). However, meta-analyses have found significant variability among probiotic formulations. In fact, many probiotic properties are thought to be strain-specific.

This study aims at providing a comprehensive characterization of a particular probiotic formula containing Lactoplantibacillus plantarum (formerly Lactobacillus plantarum) and Levilactobacillus brevis (formerly Lactobacillus brevis) in hepatic function of individuals with NAFL. The study will assess hepatic stiffness via transient elastography (Fibroscan), hepatic function via liver enzymes in serum (ALT, AST, GGT) and liver-specific inflammation via cytokeratin18 in serum, as well as some general metabolic and inflammatory markers.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Mexico city, Mexico, 14080
    • Hospital General Dr. Manuel Gea González

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Hepatic Steatosis associated with Metabolism (MAFL, also known as Non-Alcoholic Fatty Liver or NAFL) with Controlled Attenuation Parameter (CAP) value of > 269 dB / m when evaluated by Fibroscan transient elastography
• Alanine aminotransferase (ALT) levels at least 35% above the upper limit of reference values
• BMI between 25 and 40 kg / m2
• Signing of the informed consent and understanding of the procedures to be carried out
• Not willing to change their current dietary habits (hypercaloric and hyperlipemic)

Exclusion Criteria:

• Treatment of NAFL or NASH (Non-Alcoholic Steato-Hepatitis) for at least 3 months prior to the study, with high dose vitamin E (≥200 mg / day), high dose omega-3 (≥500 mg / day), pioglitazone, bile acid sequestrants, statins, GLP-1 agonists, and / or DPP4 inhibitors ("gliptins"), and not having shown a significant biochemical and ultrasonographic improvement
• History of chronic alcohol or drug abuse
• Diagnosis of infectious hepatitis or HIV infection
• Diagnosis of hemochromatosis
• Celiac disease, inflammatory bowel disease, chronic or recurrent diarrhea
• Chronic use of laxatives.
• Pancreatic failure, thyroid dysfunction, severe liver disease, biliary dysfunction (including cholecystectomy and blood bilirubin abnormalities)
• Uncontrolled diabetes or hypertriglyceridemia greater than 500mg / dL
• History of regular use (> 3 days) of oral or parenteral antibiotics one month prior to the study
• Current use of systemic corticosteroids, androgens, clopidogrel, digoxin, acenocoumarol, warfarin, phenytoin, topiramate, lithium, tricyclic antidepressants, monoamine oxidase inhibitors, second generation antipsychotics, amiodarone, tamoxifen, and/or diltiazem.
• Intake of other probiotics, plant-derived sterols, beta-glucans, red rice yeast (Monascus purpureus), or milk thistle extract (Silybum marianum) or its active ingredients (silymarin, silybin) on a regular basis (> 7 days) in the 15 days prior to entering the study.
• History of angina or cardiovascular events, cancer, or immunosuppression
• Chronic, moderate-to-heavy smoking (> 5 cigarettes a day)
• History of gastro-intestinal surgery in the previous year.
• Debilitating diseases (advanced liver or kidney disease, severe depression, psychotic symptoms, neurological diseases).
• Current pregnancy (positive urine test), or planning to become pregnant during the course of the study.
• Breastfeeding at the time of eligibility assessment
• Subjects having participated in a clinical study within 1 month prior to eligibility assessment
• Current use of 4 or more concomitant medications of any type

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Probiotic composition; A capsule containing a mix of probiotic strains (1.5 x 10^9 CFU/capsule ) administered once daily for 4 months	Dietary supplement: Probiotic composition; Mixture of two Lactoplantibacillus plantarum strains (formerly Lactobacillus plantarum) and one Levilactobacillus brevis strain (formerly Lactobacillus brevis), in a maltodextrin carrier (E1400)
Placebo Comparator: Placebo; A capsule containing placebo administered once daily for 4 months	Other: Placebo; Maltodextrin (E1400, qs)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in alanine amino transferase (ALT)	Change in serum levels (international units/L) of alanine amino transferase (ALT) across the study. Sample obtained through blood sampling	change month 2 from baseline
Change in alanine amino transferase (ALT)	Change in serum levels (international units/L) of alanine amino transferase (ALT) across the study. Sample obtained through blood sampling	change month 4 from baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hepatic steatosis	Change in the severity of the degree of hepatic steatosis measured by transient elastography with controlled attenuation parameter (Fibroscan CAP®)	change month 2 from baseline
Change in hepatic steatosis	Change in the severity of the degree of hepatic steatosis measured by transient elastography with controlled attenuation parameter (Fibroscan CAP®)	change month 4 from baseline
Change in Fibroscan-AST score	Change in the values of the Fibroscan-AST score (FAST, ranging 0-1), where higher values indicate a worse condition	change month 2 from baseline
Change in Fibroscan-AST score	Change in the values of the Fibroscan-AST score (FAST, ranging 0-1), where higher values indicate a worse condition	change month 4 from baseline
Change in Fatty Liver Index	Change in the values of the Fatty Liver Index (FLI, ranging 0-100), where higher values indicate a worse condition	change month 2 from baseline
Change in Fatty Liver Index	Change in the values of the Fatty Liver Index (FLI, ranging 0-100), where higher values indicate a worse condition	change month 4 from baseline
Change in Hepatic Steatosis Index	Change in the values of the Hepatic Steatosis Index (HSI, ranging 0-100), where higher values indicate a worse condition	change month 2 from baseline
Change in Hepatic Steatosis Index	Change in the values of the Hepatic Steatosis Index (HSI, ranging 0-100), where higher values indicate a worse condition	change month 4 from baseline
Change in Cholesterol	Change in LDL cholesterol, oxidized LDL-cholesterol, HDL-cholesterol, non-HDL cholesterol, total cholesterol. Sample obtained through blood sampling.	change month 2 from baseline
Change in Cholesterol	Change in LDL cholesterol, oxidized LDL-cholesterol, HDL-cholesterol, non-HDL cholesterol, total cholesterol. Sample obtained through blood sampling.	change month 4 from baseline
Change in leptin serum parameters	Change in leptin. Sample obtained through blood sampling.	change month 2 from baseline
Change in leptin serum parameters	Change in leptin. Sample obtained through blood sampling.	change month 4 from baseline
Change in adiponectin serum parameters	Change in adiponectin. Sample obtained through blood sampling.	change month 2 from baseline
Change in adiponectin serum parameters	Change in adiponectin. Sample obtained through blood sampling.	change month 4 from baseline
Change in HOMA serum parameters	Change in HOMA (Homeostatic Model Assessment). Sample obtained through blood sampling.	change month 2 from baseline
Change in HOMA serum parameters	Change in HOMA (Homeostatic Model Assessment). Sample obtained through blood sampling.	change month 4 from baseline
Change in glucose serum parameters	Change in glucose. Sample obtained through blood sampling.	change month 2 from baseline
Change in glucose serum parameters	Change in glucose. Sample obtained through blood sampling.	change month 4 from baseline
Change in glycosylated hemoglobin serum parameters	Change in glycosylated hemoglobin (Hb1Ac). Sample obtained through blood sampling.	change month 2 from baseline
Change in glycosylated hemoglobin serum parameters	Change in glycosylated hemoglobin (Hb1Ac). Sample obtained through blood sampling.	change month 4 from baseline
Change in insulin serum parameters	Change in insulin. Sample obtained through blood sampling.	change month 2 from baseline
Change in insulin serum parameters	Change in insulin. Sample obtained through blood sampling.	change month 4 from baseline
Change in Triglycerides serum parameters	Change in Triglycerides. Sample obtained through blood sampling.	change month 2 from baseline
Change in Triglycerides serum parameters	Change in Triglycerides. Sample obtained through blood sampling.	change month 4 from baseline
Change in ferritin serum parameters	Change in ferritin. Samples obtained through blood sampling	change month 2 from baseline
Change in ferritin serum parameters	Change in ferritin. Samples obtained through blood sampling	change month 4 from baseline
Change in C-reactive protein serum parameters	Change in ferritin. Samples obtained through blood sampling	change month 2 from baseline
Change in C-reactive protein serum parameters	Change in ferritin. Samples obtained through blood sampling	change month 4 from baseline
Change in IL-1beta serum parameters	Change in IL-1beta. Samples obtained through blood sampling	change month 2 from baseline
Change in IL-1beta serum parameters	Change in IL-1beta. Samples obtained through blood sampling	change month 4 from baseline
Change in TNF-alpha serum parameters	Change in TNF-alpha. Samples obtained through blood sampling	change month 2 from baseline
Change in TNF-alpha serum parameters	Change in TNF-alpha. Samples obtained through blood sampling	change month 4 from baseline
Change in Cytokeratin-18 serum parameters	Change in Cytokeratin-18. Samples obtained through blood sampling	change month 2 from baseline
Change in Cytokeratin-18 serum parameters	Change in Cytokeratin-18. Samples obtained through blood sampling	change month 4 from baseline
Change in IL-17 serum parameters	Change in IL-17. Samples obtained through blood sampling	change month 4 from baseline
Change in IL-17 serum parameters	Change in IL-17. Samples obtained through blood sampling	change month 2 from baseline
Intestinal microbiota composition	Change in alpha and beta diversity of the gut microbiota as assessed by 16S bacterial gene analysis	change month 4 from baseline
Change in fat values	Change in the values of total body fat and visceral fat evaluated by impedance measurement	change month 2 from baseline
Change in fat values	Change in the values of total body fat and visceral fat evaluated by impedance measurement	change month 4 from baseline
Change in waist values	Change in the values of waist circumference evaluated by impedance measurement	change month 2 from baseline
Change in waist values	Change in the values of waist circumference evaluated by impedance measurement	change month 4 from baseline
Change in waist / height index	Change in the values of waist / height index, evaluated by impedance measurement	change month 2 from baseline
Change in waist / height index	Change in the values of waist / height index, evaluated by impedance measurement	change month 4 from baseline
Change in hip circumference values	Change in the hip circumference evaluated by impedance measurement	change month 2 from baseline
Change in hip circumference values	Change in the hip circumference evaluated by impedance measurement	change month 4 from baseline
Change in BMI values	Change in the values of Body Mass Index (BMI) evaluated by impedance measurement	change month 2 from baseline
Change in BMI values	Change in the values of Body Mass Index (BMI) evaluated by impedance measurement	change month 4 from baseline
Adverse events	Frequency of adverse events	Throughout study completion, an average of 4 months

Collaborators and Investigators

• Sponsor: AB Biotics, SA

Publications and helpful links

General Publications

• Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):506-14. doi: 10.1038/nrgastro.2014.66. Epub 2014 Jun 10.
• Ma YY, Li L, Yu CH, Shen Z, Chen LH, Li YM. Effects of probiotics on nonalcoholic fatty liver disease: a meta-analysis. World J Gastroenterol. 2013 Oct 28;19(40):6911-8. doi: 10.3748/wjg.v19.i40.6911.
• Loman BR, Hernandez-Saavedra D, An R, Rector RS. Prebiotic and probiotic treatment of nonalcoholic fatty liver disease: a systematic review and meta-analysis. Nutr Rev. 2018 Nov 1;76(11):822-839. doi: 10.1093/nutrit/nuy031.
• Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, Tiribelli C. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006 Nov 2;6:33. doi: 10.1186/1471-230X-6-33.
• Lee JH, Kim D, Kim HJ, Lee CH, Yang JI, Kim W, Kim YJ, Yoon JH, Cho SH, Sung MW, Lee HS. Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis. 2010 Jul;42(7):503-8. doi: 10.1016/j.dld.2009.08.002. Epub 2009 Sep 18.
• Newsome PN, Sasso M, Deeks JJ, Paredes A, Boursier J, Chan WK, Yilmaz Y, Czernichow S, Zheng MH, Wong VW, Allison M, Tsochatzis E, Anstee QM, Sheridan DA, Eddowes PJ, Guha IN, Cobbold JF, Paradis V, Bedossa P, Miette V, Fournier-Poizat C, Sandrin L, Harrison SA. FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol. 2020 Apr;5(4):362-373. doi: 10.1016/S2468-1253(19)30383-8. Epub 2020 Feb 3. Erratum In: Lancet Gastroenterol Hepatol. 2020 Apr;5(4):e3.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2021
• Primary Completion (Actual): December 13, 2021
• Study Completion (Actual): February 22, 2022

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: March 29, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): February 24, 2022
• Last Update Submitted That Met QC Criteria: February 23, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: NAFL; MAFL
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: ABB-MAFL21A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No