Clinical trial NCT04823676: Efficacy and Safety of a Probiotic Composition as Adjunct in MAFL Management
Official title: Efficacy and Safety of a Probiotic Composition as Adjunct Treatment in the Comprehensive Management of Metabolism-Associated Hepatic Steatosis in Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non Alcoholic Fatty Liver
Keywords: NAFL
MAFL
Lead sponsor: AB Biotics, SA
Sponsor class: INDUSTRY
First posted: 2021-04-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in alanine amino transferase (ALT)
timeFrame: change month 2 from baseline
measure: Change in alanine amino transferase (ALT)
timeFrame: change month 4 from baseline
Secondary outcomes:
measure: Change in hepatic steatosis
timeFrame: change month 2 from baseline
measure: Change in hepatic steatosis
timeFrame: change month 4 from baseline
measure: Change in Fibroscan-AST score
timeFrame: change month 2 from baseline
measure: Change in Fibroscan-AST score
timeFrame: change month 4 from baseline
measure: Change in Fatty Liver Index
timeFrame: change month 2 from baseline
measure: Change in Fatty Liver Index
timeFrame: change month 4 from baseline
measure: Change in Hepatic Steatosis Index
timeFrame: change month 2 from baseline
measure: Change in Hepatic Steatosis Index
timeFrame: change month 4 from baseline
measure: Change in Cholesterol
timeFrame: change month 2 from baseline
measure: Change in Cholesterol
timeFrame: change month 4 from baseline
measure: Change in leptin serum parameters
timeFrame: change month 2 from baseline
measure: Change in leptin serum parameters
timeFrame: change month 4 from baseline
measure: Change in adiponectin serum parameters
timeFrame: change month 2 from baseline
measure: Change in adiponectin serum parameters
timeFrame: change month 4 from baseline
measure: Change in HOMA serum parameters
timeFrame: change month 2 from baseline
measure: Change in HOMA serum parameters
timeFrame: change month 4 from baseline
measure: Change in glucose serum parameters
timeFrame: change month 2 from baseline
measure: Change in glucose serum parameters
timeFrame: change month 4 from baseline
measure: Change in glycosylated hemoglobin serum parameters
timeFrame: change month 2 from baseline
measure: Change in glycosylated hemoglobin serum parameters
timeFrame: change month 4 from baseline
measure: Change in insulin serum parameters
timeFrame: change month 2 from baseline
measure: Change in insulin serum parameters
timeFrame: change month 4 from baseline
measure: Change in Triglycerides serum parameters
timeFrame: change month 2 from baseline
measure: Change in Triglycerides serum parameters
timeFrame: change month 4 from baseline
measure: Change in ferritin serum parameters
timeFrame: change month 2 from baseline
measure: Change in ferritin serum parameters
timeFrame: change month 4 from baseline
measure: Change in C-reactive protein serum parameters
timeFrame: change month 2 from baseline
measure: Change in C-reactive protein serum parameters
timeFrame: change month 4 from baseline
measure: Change in IL-1beta serum parameters
timeFrame: change month 2 from baseline
measure: Change in IL-1beta serum parameters
timeFrame: change month 4 from baseline
measure: Change in TNF-alpha serum parameters
timeFrame: change month 2 from baseline
measure: Change in TNF-alpha serum parameters
timeFrame: change month 4 from baseline
measure: Change in Cytokeratin-18 serum parameters
timeFrame: change month 2 from baseline
measure: Change in Cytokeratin-18 serum parameters
timeFrame: change month 4 from baseline
measure: Change in IL-17 serum parameters
timeFrame: change month 4 from baseline
measure: Change in IL-17 serum parameters
timeFrame: change month 2 from baseline
measure: Intestinal microbiota composition
timeFrame: change month 4 from baseline
measure: Change in fat values
timeFrame: change month 2 from baseline
measure: Change in fat values
timeFrame: change month 4 from baseline
measure: Change in waist values
timeFrame: change month 2 from baseline
measure: Change in waist values
timeFrame: change month 4 from baseline
measure: Change in waist / height index
timeFrame: change month 2 from baseline
measure: Change in waist / height index
timeFrame: change month 4 from baseline
measure: Change in hip circumference values
timeFrame: change month 2 from baseline
measure: Change in hip circumference values
timeFrame: change month 4 from baseline
measure: Change in BMI values
timeFrame: change month 2 from baseline
measure: Change in BMI values
timeFrame: change month 4 from baseline
measure: Adverse events
timeFrame: Throughout study completion, an average of 4 months
Other outcomes:
Locations:
city: Mexico city
country: Mexico
facility: Hospital General Dr. Manuel Gea Gonzalez
Study officials:
References:
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.
citation: 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.
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 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.
citation: 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.
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. Epub 2009 Sep 18.
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, 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.