Clinical trial NCT05523024: Effect of Probiotics or Berberine in Hepatic Steatosis Markers, Cardiometabolic and Microbiotic Profile in NAFL.
Official title: Effect of Probiotics or Berberine Supplementation on Hepatic Steatosis Markers, Cardiometabolic and Microbiotic Profile in NAFL - A Randomized Double- Blind Clinical Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Non Alcoholic Fatty Liver
Obesity
Keywords: NAFL; obesity; probiotics; berberine; microbiota;
Lead sponsor: Poznan University of Medical Sciences
Sponsor class: OTHER
First posted: 2022-08-31
Enrollment: 140
Sex: ALL
Minimum age (years): 40
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: Effect of oral selected Probiotics (PRO) and/or Berberine (BBR) supplementation on hepatic steatosis markers, cardiometabolic profile, and gut microbiota profile in the non-alcoholic fatty liver (NAFL) - a randomized double-blind clinical study.

Detailed description: Probiotics (PRO) and bioactive natural substances such as Berberine (BBR) can improve metabolic parameters in patients with obesity and metabolic disorders. In addition, they significantly affect the composition and function of gut microbiota (GM) and support anti-inflammation and antioxidant defense. These data have become the starting point for the proposed multidirectional approach, aimed at assessing the effect of PRO and/or BBR supplementation on:

* hepatic-related outcomes,
* changes in anthropometric measurements (body mass, BMI, body mass composition and fat mass % content),
* cardiometabolic profile (e.g. blood pressure, noninvasive markers of endothelial function, cardiometabolic biochemical parameters)
* microbiotic profile (gut microbiota composition, endotoxemia)
* the content of the minerals, in overweight/obese patients with nonalcoholic fatty liver (NAFL).

Eligibility criteria: Inclusion Criteria:

* age 40 to 60 years;
* women ≥1 year since last menstruation;
* body mass index (BMI): 27.0 kg/m2 to 34.9 kg/m2;
* abdominal obesity-related waist circumference \> 80 cm (women) and \>94 cm (men) (in accordance to International Diabetes Federation);
* stable body weight in the 3 months prior to the trial (permissible deviation is ± 3 kg);
* NAFL - diagnosed based on USG in accordance with PGE-NAFLD recommendation

Exclusion Criteria:

* history of following alternative diets within 3 months before the study;
* history of use of any dietary supplements in the 3 months before the study;
* history of intake of antibiotics, probiotics, prebiotics within 3 months before the study;
* secondary form of obesity, pharmacological treatment for obesity (in the 3 months before the study), history of bariatric surgery;
* another liver diseases: high risk of NASH (assessed on the FIB-4, according to the PGE-NAFLD recommendation), autoimmune hepatitis, hepatitis B and C, toxic hepatitis, cirrhosis, Wilson's disease, hemochromatosis;
* other gastrointestinal disorders, especially: IBD, celiac disease, gastritis and duodenitis, pancreatic disorders, gastrointestinal symptoms suggestive of IBS;
* clinically significant acute inflammatory process (elevated hsCRP);
* abnormal kidney function (GFR \<60mL/min/1,73m2);
* T2D;
* dyslipidemia or hypertension - requiring the introduction and/or change of pharmacological treatment in the 6 months before the trial or during intervention;
* pump inhibitors, anticoagulants, drugs causing metabolic alteration, e.g., SFAs (second-generation antipsychotics);
* diseases requiring nutritional requirement and chronic supplementation;
* alcohol (\>30g/d for men and \>20g/d for women), nicotine or drug abuse;
* mental disorders, including eating disorders;
* cancer, autoimmune diseases;
* any other condition which may influence on final results of the study or pose a risk for subjects health.

Primary outcomes:
measure: Changes in Fibrosis-4 (FIB-4) - Index for Liver Fibrosis.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in HSI - Hepatic Steatosis Index.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in NAFLD-LFS (liver fat score).
timeFrame: At the baseline and 12 weeks of treatment
Secondary outcomes:
measure: Changes in blood pressure.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in weight.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in waist circumference, hip circumference.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in waist to hip ratio.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in BMI.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in fat mass content in the body.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in pulse wave velocity (PWV).
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in pulse wave analysis (PWA).
timeFrame: At the baseline and 12 weeks of treatment
measure: Gut (taxonomic and functional) microbiota analysis in stool.
timeFrame: At the baseline and 12 weeks of treatment
measure: Short-chain fatty acids (SCFAs) concentration in stool.
timeFrame: At the baseline and 12 weeks of treatment
measure: Measurement of hair minerals (Fe, Mg, Ca, Cu, Zn) concentration.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in ALT, AST, GGT
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in non-esterified free fatty acids.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in lipids profile (TC, HDL, TG).
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in low-density lipoprotein (LDL).
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in fasting glucose level.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in fasting insulin level.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in insulin resistance index (HOMA-IR)
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in parameter of liver damage: cytokeratin 18.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in parameter of liver damage: Glutathione S-transferase (GST).
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in parameter of liver damage: collagen IV.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in parameter of liver damage: hyaluronic acid.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in hsCRP.
timeFrame: At the baseline and 12 weeks of treatment
measure: Changes in pentraxin 3.
timeFrame: At the baseline and 12 weeks of treatment
measure: Gut barrier integrity parameter: calprotectin.
timeFrame: At the baseline and 12 weeks of treatment
measure: Gut barrier integrity parameters: liver fatty acid-binding protein (L-FABP), intestinal fatty acid-binding protein (I-FABP).
timeFrame: At the baseline and 12 weeks of treatment
measure: Gut barrier integrity parameters: lipopolysaccharide (LPS).
timeFrame: At the baseline and 12 weeks of treatment
measure: Cardiometabolic risk.
timeFrame: At the baseline and 12 weeks of treatment
Other outcomes:
Locations:
city: Poznań
country: Poland
facility: 2 Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznań University of Medical Sciences,
Study officials:
affiliation: Poznan University of Medical Sciences, Poznan, Poland
name: Paweł Bogdański, Professor
role: PRINCIPAL_INVESTIGATOR
References: