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

Non Alcoholic Fatty Liver Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04823676
• Other study ID #: ABB-MAFL21A
• Status: Completed
• Phase: N/A
• Start date: March 31, 2021
• Est. completion date: February 22, 2022

Study information

• Verified date: February 2022
• Source: AB Biotics, SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: February 22, 2022
• Est. primary completion date: December 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• Non Alcoholic Fatty Liver
• Non-alcoholic Fatty Liver Disease

Intervention

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)

Other:
• Placebo
Maltodextrin (E1400, qs)

Locations

Country	Name	City	State
Mexico	Hospital General Dr. Manuel Gea Gonzalez	Mexico city

Sponsors (1)

Lead Sponsor	Collaborator
AB Biotics, SA

Country where clinical trial is conducted

Mexico, 

References & Publications (6)

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. — View Citation

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 sco — View Citation

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. Epu — View Citation

Loman BR, Hernández-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. — View Citation

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. Review. — View Citation

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, Harri — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in leptin serum parameters	Change in leptin. Sample obtained through blood sampling.	change month 2 from baseline
Secondary	Change in leptin serum parameters	Change in leptin. Sample obtained through blood sampling.	change month 4 from baseline
Secondary	Change in adiponectin serum parameters	Change in adiponectin. Sample obtained through blood sampling.	change month 2 from baseline
Secondary	Change in adiponectin serum parameters	Change in adiponectin. Sample obtained through blood sampling.	change month 4 from baseline
Secondary	Change in HOMA serum parameters	Change in HOMA (Homeostatic Model Assessment). Sample obtained through blood sampling.	change month 2 from baseline
Secondary	Change in HOMA serum parameters	Change in HOMA (Homeostatic Model Assessment). Sample obtained through blood sampling.	change month 4 from baseline
Secondary	Change in glucose serum parameters	Change in glucose. Sample obtained through blood sampling.	change month 2 from baseline
Secondary	Change in glucose serum parameters	Change in glucose. Sample obtained through blood sampling.	change month 4 from baseline
Secondary	Change in glycosylated hemoglobin serum parameters	Change in glycosylated hemoglobin (Hb1Ac). Sample obtained through blood sampling.	change month 2 from baseline
Secondary	Change in glycosylated hemoglobin serum parameters	Change in glycosylated hemoglobin (Hb1Ac). Sample obtained through blood sampling.	change month 4 from baseline
Secondary	Change in insulin serum parameters	Change in insulin. Sample obtained through blood sampling.	change month 2 from baseline
Secondary	Change in insulin serum parameters	Change in insulin. Sample obtained through blood sampling.	change month 4 from baseline
Secondary	Change in Triglycerides serum parameters	Change in Triglycerides. Sample obtained through blood sampling.	change month 2 from baseline
Secondary	Change in Triglycerides serum parameters	Change in Triglycerides. Sample obtained through blood sampling.	change month 4 from baseline
Secondary	Change in ferritin serum parameters	Change in ferritin. Samples obtained through blood sampling	change month 2 from baseline
Secondary	Change in ferritin serum parameters	Change in ferritin. Samples obtained through blood sampling	change month 4 from baseline
Secondary	Change in C-reactive protein serum parameters	Change in ferritin. Samples obtained through blood sampling	change month 2 from baseline
Secondary	Change in C-reactive protein serum parameters	Change in ferritin. Samples obtained through blood sampling	change month 4 from baseline
Secondary	Change in IL-1beta serum parameters	Change in IL-1beta. Samples obtained through blood sampling	change month 2 from baseline
Secondary	Change in IL-1beta serum parameters	Change in IL-1beta. Samples obtained through blood sampling	change month 4 from baseline
Secondary	Change in TNF-alpha serum parameters	Change in TNF-alpha. Samples obtained through blood sampling	change month 2 from baseline
Secondary	Change in TNF-alpha serum parameters	Change in TNF-alpha. Samples obtained through blood sampling	change month 4 from baseline
Secondary	Change in Cytokeratin-18 serum parameters	Change in Cytokeratin-18. Samples obtained through blood sampling	change month 2 from baseline
Secondary	Change in Cytokeratin-18 serum parameters	Change in Cytokeratin-18. Samples obtained through blood sampling	change month 4 from baseline
Secondary	Change in IL-17 serum parameters	Change in IL-17. Samples obtained through blood sampling	change month 4 from baseline
Secondary	Change in IL-17 serum parameters	Change in IL-17. Samples obtained through blood sampling	change month 2 from baseline
Secondary	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
Secondary	Change in fat values	Change in the values of total body fat and visceral fat evaluated by impedance measurement	change month 2 from baseline
Secondary	Change in fat values	Change in the values of total body fat and visceral fat evaluated by impedance measurement	change month 4 from baseline
Secondary	Change in waist values	Change in the values of waist circumference evaluated by impedance measurement	change month 2 from baseline
Secondary	Change in waist values	Change in the values of waist circumference evaluated by impedance measurement	change month 4 from baseline
Secondary	Change in waist / height index	Change in the values of waist / height index, evaluated by impedance measurement	change month 2 from baseline
Secondary	Change in waist / height index	Change in the values of waist / height index, evaluated by impedance measurement	change month 4 from baseline
Secondary	Change in hip circumference values	Change in the hip circumference evaluated by impedance measurement	change month 2 from baseline
Secondary	Change in hip circumference values	Change in the hip circumference evaluated by impedance measurement	change month 4 from baseline
Secondary	Change in BMI values	Change in the values of Body Mass Index (BMI) evaluated by impedance measurement	change month 2 from baseline
Secondary	Change in BMI values	Change in the values of Body Mass Index (BMI) evaluated by impedance measurement	change month 4 from baseline
Secondary	Adverse events	Frequency of adverse events	Throughout study completion, an average of 4 months