Non Alcoholic Fatty Liver
Conditions
Keywords
NAFL, MAFL
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.
Interventions
DIETARY_SUPPLEMENTProbiotic composition
Mixture of two Lactoplantibacillus plantarum strains (formerly Lactobacillus plantarum) and one Levilactobacillus brevis strain (formerly Lactobacillus brevis), in a maltodextrin carrier (E1400)
OTHERPlacebo
Maltodextrin (E1400, qs)
Sponsors
AB Biotics, SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Active and placebo capsules are indistinguishable in form, color and taste, and provided in coded boxes. List containing the correspondence between codes and treatment group assignment is prepared by a pharmacist not participating in the study and kept in a sealed envelope until the end of the study.
Intervention model description
Randomized, double-blind, placebo-controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in alanine amino transferase (ALT) | change month 2 from baseline | Change in serum levels (international units/L) of alanine amino transferase (ALT) across the study. Sample obtained through blood sampling |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in hepatic steatosis | change month 2 from baseline | Change in the severity of the degree of hepatic steatosis measured by transient elastography with controlled attenuation parameter (Fibroscan CAP®) |
| Change in Fibroscan-AST score | change month 2 from baseline | Change in the values of the Fibroscan-AST score (FAST, ranging 0-1), where higher values indicate a worse condition |
| Change in Fatty Liver Index | change month 2 from baseline | Change in the values of the Fatty Liver Index (FLI, ranging 0-100), where higher values indicate a worse condition |
| Change in Hepatic Steatosis Index | change month 2 from baseline | Change in the values of the Hepatic Steatosis Index (HSI, ranging 0-100), where higher values indicate a worse condition |
| Change in Cholesterol | change month 2 from baseline | Change in LDL cholesterol, oxidized LDL-cholesterol, HDL-cholesterol, non-HDL cholesterol, total cholesterol. Sample obtained through blood sampling. |
| Change in leptin serum parameters | change month 2 from baseline | Change in leptin. Sample obtained through blood sampling. |
| Change in adiponectin serum parameters | change month 2 from baseline | Change in adiponectin. Sample obtained through blood sampling. |
| Change in HOMA serum parameters | change month 2 from baseline | Change in HOMA (Homeostatic Model Assessment). Sample obtained through blood sampling. |
| Change in glucose serum parameters | change month 2 from baseline | Change in glucose. Sample obtained through blood sampling. |
| Change in glycosylated hemoglobin serum parameters | change month 2 from baseline | Change in glycosylated hemoglobin (Hb1Ac). Sample obtained through blood sampling. |
| Change in insulin serum parameters | change month 2 from baseline | Change in insulin. Sample obtained through blood sampling. |
| Change in ferritin serum parameters | change month 2 from baseline | Change in ferritin. Samples obtained through blood sampling |
| Change in Triglycerides serum parameters | change month 2 from baseline | Change in Triglycerides. Sample obtained through blood sampling. |
| Change in IL-1beta serum parameters | change month 2 from baseline | Change in IL-1beta. Samples obtained through blood sampling |
| Change in TNF-alpha serum parameters | change month 2 from baseline | Change in TNF-alpha. Samples obtained through blood sampling |
| Change in Cytokeratin-18 serum parameters | change month 2 from baseline | Change in Cytokeratin-18. Samples obtained through blood sampling |
| Change in IL-17 serum parameters | change month 4 from baseline | Change in IL-17. Samples obtained through blood sampling |
| Intestinal microbiota composition | change month 4 from baseline | Change in alpha and beta diversity of the gut microbiota as assessed by 16S bacterial gene analysis |
| Change in fat values | change month 2 from baseline | Change in the values of total body fat and visceral fat evaluated by impedance measurement |
| Change in waist values | change month 2 from baseline | Change in the values of waist circumference evaluated by impedance measurement |
| Change in waist / height index | change month 2 from baseline | Change in the values of waist / height index, evaluated by impedance measurement |
| Change in hip circumference values | change month 2 from baseline | Change in the hip circumference evaluated by impedance measurement |
| Change in BMI values | change month 2 from baseline | Change in the values of Body Mass Index (BMI) evaluated by impedance measurement |
| Adverse events | Throughout study completion, an average of 4 months | Frequency of adverse events |
| Change in C-reactive protein serum parameters | change month 2 from baseline | Change in ferritin. Samples obtained through blood sampling |
Countries
Mexico
Outcome results
None listed