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.

NCT ID: NCT07025980

Last Updated: 2025-06-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-01
• Study Completion Date: 2029-07-31

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.

Conditions

MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis); Diabetes Mellitus; Hypertension; Hyperlipidaemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

test group

Test group (n 57) The test product is a ready-to-use preparation PROBalansHepatocare, manufactured by PharmaS d.o.o., which contains 8 strains of live cultures of microorganisms (Bifidobacteriumbreve BBR8, Bifidobacteriuminfantis SP37, Bifidobacteriumlongum SP54, Lactobacillus acidophilus LA1, Lactobacillus bulgaricus LB2, Lactobacillus paracasei IMC502®, Lactobacillus plantarum BG 112, Streptococcusthermophilus SP4) with about 100 billion bacteria (50x109 CFU/capsule) in two capsules per day. In addition, the test product contains 100 mg of fructooligosaccharides, 210 mg of Ca-butyrate, and 10 ug (400 IU) of vitamin D in each capsule.

Group Type: EXPERIMENTAL

The test product is a ready-to-use sinbiotic preparation of multispecies probiotics, ca-butyrate and FOS

Intervention Type: DIETARY_SUPPLEMENT

The test product is a ready-to-use preparation PROBalansHepatocare, manufactured by PharmaS d.o.o., which contains 8 strains of live cultures of microorganisms (Bifidobacteriumbreve BBR8, Bifidobacteriuminfantis SP37, Bifidobacteriumlongum SP54, Lactobacillus acidophilus LA1, Lactobacillus bulgaricus LB2, Lactobacillus paracasei IMC502®, Lactobacillus plantarum BG 112, Streptococcusthermophilus SP4) with about 100 billion bacteria (50x109 CFU/capsule) in two capsules per day. In addition, the test product contains 100 mg of fructooligosaccharides, 210 mg of Ca-butyrate, and 10 ug (400 IU) of vitamin D in each capsule.

Placebo

Placebo group (n 57)The placebo is identical to the test product in all aspects (organoleptic), but contains only excipients (cellulose; hydroxypropyl-methyl cellulose) and 10 ug (400 IU) of vitamin D.

Group Type: PLACEBO_COMPARATOR

Placebo Drug

Intervention Type: DIETARY_SUPPLEMENT

Contains only excipients (cellulose; hydroxypropyl-methyl cellulose) and 10 ug (400 IU) of vitamin D. They do not contain dyes, flavors or preservatives, and contain traces of soy and milk, the levels of which do not affect people who are lactose intolerant.

Interventions

The test product is a ready-to-use sinbiotic preparation of multispecies probiotics, ca-butyrate and FOS

The test product is a ready-to-use preparation PROBalansHepatocare, manufactured by PharmaS d.o.o., which contains 8 strains of live cultures of microorganisms (Bifidobacteriumbreve BBR8, Bifidobacteriuminfantis SP37, Bifidobacteriumlongum SP54, Lactobacillus acidophilus LA1, Lactobacillus bulgaricus LB2, Lactobacillus paracasei IMC502®, Lactobacillus plantarum BG 112, Streptococcusthermophilus SP4) with about 100 billion bacteria (50x109 CFU/capsule) in two capsules per day. In addition, the test product contains 100 mg of fructooligosaccharides, 210 mg of Ca-butyrate, and 10 ug (400 IU) of vitamin D in each capsule.

Intervention Type: DIETARY_SUPPLEMENT

Placebo Drug

Contains only excipients (cellulose; hydroxypropyl-methyl cellulose) and 10 ug (400 IU) of vitamin D. They do not contain dyes, flavors or preservatives, and contain traces of soy and milk, the levels of which do not affect people who are lactose intolerant.

Intervention Type: DIETARY_SUPPLEMENT

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

General Hospital Šibenik, Croatia

OTHER

Sponsor Role: collaborator

General Hospital Zadar

OTHER

Sponsor Role: collaborator

University Hospital Dubrava

OTHER

Sponsor Role: collaborator

University Hospital Rijeka

OTHER

Sponsor Role: collaborator

Clinical Hospital Merkur

OTHER

Sponsor Role: collaborator

University Hospital Sestre Milosrdnice

OTHER

Sponsor Role: collaborator

University Hospital of Split

OTHER

Sponsor Role: collaborator

Eva Cubric

OTHER

Sponsor Role: lead

Responsible Party

Eva Cubric

doctor medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Marko Skelin, ass.prof.dr.sc, mag.pharm.

Role: STUDY_CHAIR

GH Sibenik-Knin County, Medical Faculty University of Rijeka, Croatia

Locations

General Hospital Sibenik-Knin County

Šibenik, Croatia, Croatia

Countries

Croatia

Central Contacts

Eva Cubric, doctor of medicine

Role: CONTACT

gastroenterologija@bolnica-sibenik.hr

+38522641465

Marko Skelin, doctor of science, magh.pharm

Role: CONTACT

marko.skelin@uniri.hr

+38522641641

Facility Contacts

Eva Cubric, doctor of medicine

Role: primary

gastroenterologija@bolnica-sibenik.hr

+38522641465

Marko Skelin, PHD, mag.pharm

Role: backup

marko.skelin@uniri.hr

+38522641641

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Other Identifiers

01-22682/1-23

Identifier Type: -

Identifier Source: org_study_id