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

Not Applicable
Completed
Conditions
Non Alcoholic Fatty Liver
Interventions
Other: Placebo
Dietary Supplement: Probiotic composition
Registration Number
NCT04823676
Lead Sponsor
AB Biotics, SA
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboA capsule containing placebo administered once daily for 4 months
Probiotic compositionProbiotic compositionA capsule containing a mix of probiotic strains (1.5 x 10\^9 CFU/capsule ) administered once daily for 4 months
Primary Outcome Measures
NameTimeMethod
Change in alanine amino transferase (ALT)change month 4 from baseline

Change in serum levels (international units/L) of alanine amino transferase (ALT) across the study. Sample obtained through blood sampling

Secondary Outcome Measures
NameTimeMethod
Change in Fatty Liver Indexchange month 4 from baseline

Change in the values of the Fatty Liver Index (FLI, ranging 0-100), where higher values indicate a worse condition

Change in leptin serum parameterschange month 4 from baseline

Change in leptin. Sample obtained through blood sampling.

Change in Hepatic Steatosis Indexchange month 4 from baseline

Change in the values of the Hepatic Steatosis Index (HSI, ranging 0-100), where higher values indicate a worse condition

Change in Cholesterolchange month 4 from baseline

Change in LDL cholesterol, oxidized LDL-cholesterol, HDL-cholesterol, non-HDL cholesterol, total cholesterol. Sample obtained through blood sampling.

Change in Fibroscan-AST scorechange month 4 from baseline

Change in the values of the Fibroscan-AST score (FAST, ranging 0-1), where higher values indicate a worse condition

Change in hepatic steatosischange month 4 from baseline

Change in the severity of the degree of hepatic steatosis measured by transient elastography with controlled attenuation parameter (Fibroscan CAP®)

Change in adiponectin serum parameterschange month 4 from baseline

Change in adiponectin. Sample obtained through blood sampling.

Change in HOMA serum parameterschange month 4 from baseline

Change in HOMA (Homeostatic Model Assessment). Sample obtained through blood sampling.

Change in glucose serum parameterschange month 4 from baseline

Change in glucose. Sample obtained through blood sampling.

Change in glycosylated hemoglobin serum parameterschange month 4 from baseline

Change in glycosylated hemoglobin (Hb1Ac). Sample obtained through blood sampling.

Change in C-reactive protein serum parameterschange month 4 from baseline

Change in ferritin. Samples obtained through blood sampling

Change in Cytokeratin-18 serum parameterschange month 4 from baseline

Change in Cytokeratin-18. Samples obtained through blood sampling

Intestinal microbiota compositionchange month 4 from baseline

Change in alpha and beta diversity of the gut microbiota as assessed by 16S bacterial gene analysis

Change in waist / height indexchange month 4 from baseline

Change in the values of waist / height index, evaluated by impedance measurement

Change in insulin serum parameterschange month 4 from baseline

Change in insulin. Sample obtained through blood sampling.

Change in Triglycerides serum parameterschange month 4 from baseline

Change in Triglycerides. Sample obtained through blood sampling.

Change in ferritin serum parameterschange month 4 from baseline

Change in ferritin. Samples obtained through blood sampling

Change in BMI valueschange month 4 from baseline

Change in the values of Body Mass Index (BMI) evaluated by impedance measurement

Change in IL-1beta serum parameterschange month 4 from baseline

Change in IL-1beta. Samples obtained through blood sampling

Change in waist valueschange month 4 from baseline

Change in the values of waist circumference evaluated by impedance measurement

Change in hip circumference valueschange month 4 from baseline

Change in the hip circumference evaluated by impedance measurement

Adverse eventsThroughout study completion, an average of 4 months

Frequency of adverse events

Change in TNF-alpha serum parameterschange month 4 from baseline

Change in TNF-alpha. Samples obtained through blood sampling

Change in IL-17 serum parameterschange month 2 from baseline

Change in IL-17. Samples obtained through blood sampling

Change in fat valueschange month 4 from baseline

Change in the values of total body fat and visceral fat evaluated by impedance measurement

Trial Locations

Locations (1)

Hospital General Dr. Manuel Gea Gonzalez

🇲🇽

Mexico city, Mexico

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