Clinical trial NCT07025980: Effect of Sinbiotic With Multispecies Probiotics on Liver Parameters Liver Enzymes, Ultrasound, Elastography and Adipokines in Same Cases) in Patients With Metabolic Associated Steatotic Liver Disease.
Official title: Effect of Sinbiotic With Multispecies Probiotics on Liver Parameters in Patients With Metabolic Associated Steatotic Liver Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis)
Diabetes Mellitus
Hypertension
Hyperlipidaemia
Keywords: elastography; human LRG1, liver enzymes, metabolic- dysfuncion steatotic liver disease, metabolic syndrome; probiotics, treatment
Lead sponsor: General Hospital Šibenik, Croatia
Sponsor class: OTHER
Collaborators: name: General Hospital Šibenik, Croatia
name: General Hospital Zadar
name: University Hospital Dubrava
name: University Hospital Rijeka
name: Clinical Hospital Merkur
name: University Hospital Sestre Milosrdnice
name: University Hospital of Split
First posted: 2025-06-18
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, multicenter, double-blind clinical trial. If they meet the inclusion criteria at the next medical examination (study start-randomization period) upon entering the study, patients will be randomized into two groups in a 1:1 ratio, where one group will receive the test product (n=57) and the other/control group placebo (n=57).
Primary purpose: TREATMENT

Brief summary: Scientific hypothesis: the use of a synbiotic preparation with a multi-strain probiotic in patients with MASLD can lead to a decrease in non-invasive elastographic parameters of hepatic steatosis and fibrosis and an improvement in liver function.

The main objective of this study is to examine whether the test product affects the improvement of liver function measured by elastographic parameters or at least the prevention of further disease progression.

The goal of this clinical trial is to learn if sinbiotics works to improve liver function in adult patients with MASLD The main questions it aims to answer are:

Does sinbiotic lowers elastographic parameters od steatosis and fibrosis? Does it change liver function by lowering liver enzymes, blood lipids and sugar? Can sinbiotics lower CV risks and improve quality of life? Researchers will compare sinbiotic to a placebo (a look-alike substance that contains no drug) to see if sinbiotic works in MASLD patients.

Participants will:

Take sinbiotic or a placebo every day (td) for 9 months Visit the clinic once every 3 months for checkups, and at the begining and after 9 months for blood tests and US with elastography Keep a diary of their symptoms, diet, activity

Detailed description: This is a randomized, multicenter, double-blind 1:1 clinical study lasting 3 years, which is planned to begin on January 2, 2025. The study will include 114 patients of both sexes over the age of 18, who suffer from MASLD and are monitored in the gastroenterology and/or endocrinology outpatient department of the Šibenik-Knin County General Hospital and cooperating institutions (Sestara milosrdnica Clinical Hospital, Split Clinical Hospital, Dubrava Clinical Hospital, Merkur Clinical Hospital, Požega General and County Hospital, Zadar General Hospital, Rijeka Clinical Hospital). Patients will take the prepared preparation (synbiotic or placebo) for 36 weeks at a dose of 2x1 capsule per day. During the study, they will keep a diary of consumption and possible side effects, and every three months they will pick up coded packages of the preparation at the gastroenterology clinic of their institution. Cooperation will be checked by telephone calls and by reviewing the diary at monthly intervals, and more often if necessary. Patients will regularly take their usual chronic therapy, especially antihypertensives, antidiabetics, and hypolipidemics, they will be recommended appropriate physical activity during the week and a diet in accordance with the recommendations of professional societies, and the use of herbal preparations and other dietary supplements is prohibited. Serum samples will be taken from the patients at the beginning of the study and at the end of the intervention for routine biochemical tests, and for the ELISA test of human LRG1 and adiponectin in some centers (after 9 months of using the test preparation or placebo). In addition to the above, an ultrasound of the liver, Fibrocan, and in some centers elastography on an Aloka Arietta ultrasound system will be performed in the same interval. All patients will have their BMI, waist circumference, and arterial pressure values measured using a standard method, and they will complete a questionnaire on quality of life and the SCORE2 CV risk table.

Eligibility criteria: Inclusion Criteria:

* MASLD confirmed by ultrasound and elastography with CAP \> 260 dB/m/MHz;
* other causes of chronic liver disease excluded and/or diagnosis confirmed by liver biopsy,
* presence of metabolic syndrome according to the definition of the International Diabetes Federation (IDF): waist circumference for women over 80 cm or over 94 cm for men, and at least two of the other criteria (treated hypertensive or blood pressure \> 130/85 mmHg determined during inclusion; treated diabetic or newly detected fasting serum glucose levels \> 5.6 mmol/l; treated dyslipidemia or newly detected serum triglyceride levels \> 1.7 mmol/L or HDL \< 1.29 mmol/L for women/\< 1.03 mmol/L for men),
* signed informed consent.

Exclusion Criteria:

* pregnancy,
* significant alcohol intake (\>30g/day in men, \>20g/day in women),
* presence of autoimmune, viral, cholestatic (primary biliary cholangitis, primary sclerosing cholangitis, obstructive biliary tree diseases) or metabolic (hemochromatosis, Wilson) causes of chronic liver disease, transplant patients, malignant diseases, free fluid in the abdomen, significant small bowel resections,
* signs of liver cirrhosis or LSM\>13 kPa measured TE,
* use of medications that can promote the development of steatosis (e.g. corticosteroids, high doses of estrogen, methotrexate, amiodarone, valproate), and medications that can affect the composition of the microbiota for at least 3 months before the start of the study (antibiotics and probiotics),
* inability to reliably measure CAP and LSM (IQR/median\>30%),
* severe psychiatric patients in whom cooperation and consent are questionable.

Primary outcomes:
measure: change in the controlled attenuated coefficient CAP (dB/m/MHZ) for steatosis
timeFrame: at baseline and after 270 days of intervention*
measure: change in liver stiffness measurement (LSM) (kPa) measured by transient elastography for fibrosis
timeFrame: at baseline and after 270 days of intervention
Secondary outcomes:
measure: change in serum levels of aspartate aminotransferase AST (U/L), alanine transferase ALT (U/L), gamma-glutamyl transferase GGT (U/L), ferritin (ng/ml)
timeFrame: at baseline and after 270 days
measure: change in serum levels of glucose (mmol/l) and fasting insulin (pmol/L), calculation of insulin resistance using the Homeostatic Model Assessment for Insulin Resistance formula HOMA-IR (glucose (mmol/l) x insulin (pmol/L)/22.5)
timeFrame: at baseline and after 270 days
measure: change in serum levels of cholesterol (mmol/L), triglycerides (mmol/L), HDL-cholesterol (mmol/L) and LDL-cholesterol (mmol/L)
timeFrame: at baseline and after 270 days
measure: change in waist circumference (cm) and body mass index (BMI=body weight (kg)/body height2(m)), kg/m2)
timeFrame: at baseline and after 270 days
measure: change in blood pressure (mmHg) measured by standard method
timeFrame: at baseline and after 270 days
measure: change in human Leucin-rich alpha-2-gylcoprotein 1 (LRG1) (ng/ml)
timeFrame: at baseline and after 270 days
measure: change in fecal calprotectin (ug/g)
timeFrame: at baseline and after 270 days
measure: change in controlled attenuated coefficient ATT (dB/cm/MHZ) for steatosis
timeFrame: at baseline and after 270 days of intervention*
measure: change in liver stiffness (Elastography) E (kPa) measured by 2D SWE for fibrosis
timeFrame: at baseline and after 270 days of intervention
measure: change in cardiovascular risk according to the European Society of Cardiology SCORE-2 tables
timeFrame: at baseline and after 270 days
measure: change in quality of life according to the validated WHO SF-36 Quality of Life Questionnaire
timeFrame: at baseline and after 270 days
measure: change in serum adiponectin levels (ng/ml)
timeFrame: at baseline and after 270 days (only on Sibenik patients)
Other outcomes:
Locations:
city: Šibenik
country: Croatia
facility: General Hospital Sibenik-Knin County
Study officials:
affiliation: GH Sibenik-Knin County, Medical Faculty University of Rijeka, Croatia
name: Marko Skelin, ass.prof.dr.sc, mag.pharm.
role: STUDY_CHAIR
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