MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis)Phase 2NCT07025980

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.

A Phase 2 study testing The test product is a ready-to-use sinbiotic preparation of multispecies probiotics, ca-butyrate and FOS in people with MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis) and Diabetes Mellitus, run by Eva Cubric at 1 site in Croatia.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis), Diabetes Mellitus, Hypertension
What is being tested?: The test product is a ready-to-use sinbiotic preparation of multispecies probiotics, ca-butyrate and FOS
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 114 participants
Where: 1 siteCroatia
Study dates: 1 Jul 2025to 31 Jul 2029
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Eva Cubric, doctor of medicine contact

+38522641465

gastroenterologija@bolnica-sibenik.hr

Marko Skelin, doctor of science, magh.pharm contact

+38522641641

marko.skelin@uniri.hr

Croatia1 site

General Hospital Sibenik-Knin County
Šibenik, Croatia, 22000
Eva Cubric, doctor of medicine, +38522641465, gastroenterologija@bolnica-sibenik.hr
Marko Skelin, PHD, mag.pharm, +38522641641, marko.skelin@uniri.hr

Other trials in Croatia

About this study

Official title: Effect of Sinbiotic With Multispecies Probiotics on Liver Parameters in Patients With Metabolic Associated Steatotic Liver Disease

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

Read the 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
Being tested: The test product is a ready-to-use sinbiotic preparation of multispecies probiotics, ca-butyrate and FOS, Placebo Drug
Keywords: elastography; human LRG1, liver enzymes, metabolic- dysfuncion steatotic liver disease, metabolic syndrome; probiotics, treatment
Medical subject headings: Diabetes Mellitus, Hypertension, Hyperlipidemias, Metabolic Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT07025980
Study group	Role	What they receive
test group	Experimental	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. Receives: Dietary Supplement: The test product is a ready-to-use sinbiotic preparation of multispecies probiotics, ca-butyrate and FOS
Placebo	Placebo comparator	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. Receives: Dietary Supplement: Placebo Drug

What is being measured

The primary outcome is the main question the study is designed to answer.

change in the controlled attenuated coefficient CAP (dB/m/MHZ) for steatosis
Measured: at baseline and after 270 days of intervention*
change in liver stiffness measurement (LSM) (kPa) measured by transient elastography for fibrosis
(1st and 2nd measured on FibroScan device, manufacturer Echosens, Paris, France)
Measured: at baseline and after 270 days of intervention

Secondary outcomes (12)

change in serum levels of aspartate aminotransferase AST (U/L), alanine transferase ALT (U/L), gamma-glutamyl transferase GGT (U/L), ferritin (ng/ml)
Measured: at baseline and after 270 days
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)
Measured: at baseline and after 270 days
change in serum levels of cholesterol (mmol/L), triglycerides (mmol/L), HDL-cholesterol (mmol/L) and LDL-cholesterol (mmol/L)
Measured: at baseline and after 270 days
change in waist circumference (cm) and body mass index (BMI=body weight (kg)/body height2(m)), kg/m2)
Measured: at baseline and after 270 days
change in blood pressure (mmHg) measured by standard method
Measured: at baseline and after 270 days
change in human Leucin-rich alpha-2-gylcoprotein 1 (LRG1) (ng/ml)
ELISA test BIOSOURCE
Measured: at baseline and after 270 days
change in fecal calprotectin (ug/g)
Measured: at baseline and after 270 days
change in controlled attenuated coefficient ATT (dB/cm/MHZ) for steatosis
Measured: at baseline and after 270 days of intervention*
change in liver stiffness (Elastography) E (kPa) measured by 2D SWE for fibrosis
ATT and E measured on Aloka Arrieta US system, by FUJI; Tokyo, Japan
Measured: at baseline and after 270 days of intervention
change in cardiovascular risk according to the European Society of Cardiology SCORE-2 tables
SCORE-2 tables for high risk population
Measured: at baseline and after 270 days
change in quality of life according to the validated WHO SF-36 Quality of Life Questionnaire
Measured: at baseline and after 270 days
change in serum adiponectin levels (ng/ml)
ELISA human test, Biosource
Measured: at baseline and after 270 days (only on Sibenik patients)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jul 202531 Jul 2029

First posted18 Jun 2025
Study start1 Jul 2025 (estimated)
Primary completion31 Jul 2028 (estimated)
Study completion31 Jul 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (12)Papers the sponsor has linked to this study.
Other trials for MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
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).
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 114 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07025980
Sponsor's protocol ID: 01-22682/1-23
Status last verified: Jun 2025
First submitted: 10 Jun 2025
Last updated: 18 Jun 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: It will not be shared in public, but by the individual request, and only after the approval of each institution in collaboration (as Ethics Commities of each institution has demand)

Publications

Lukenda Zanko V, Domislovic V, Trkulja V, Krznaric-Zrnic I, Turk-Wensveen T, Krznaric Z, Filipec Kanizaj T, Radic-Kristo D, Bilic-Zulle L, Orlic L, Dinjar-Kujundzic P, Poropat G, Stimac D, Hauser G, Mikolasevic I. Vitamin D for treatment of non-alcoholic fatty liver disease detected by transient elastography: A randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2020 Nov;22(11):2097-2106. doi: 10.1111/dom.14129. Epub 2020 Aug 5.
PubMed 32613718
Fogacci F, Giovannini M, Di Micoli V, Grandi E, Borghi C, Cicero AFG. Effect of Supplementation of a Butyrate-Based Formula in Individuals with Liver Steatosis and Metabolic Syndrome: A Randomized Double-Blind Placebo-Controlled Clinical Trial. Nutrients. 2024 Jul 28;16(15):2454. doi: 10.3390/nu16152454.
PubMed 39125336
Silva RSD, Mendonca IP, Paiva IHR, Souza JRB, Peixoto CA. Fructooligosaccharides and galactooligosaccharides improve hepatic steatosis via gut microbiota-brain axis modulation. Int J Food Sci Nutr. 2023 Nov;74(7):760-780. doi: 10.1080/09637486.2023.2262779. Epub 2023 Nov 15.
PubMed 37771001
Duseja A, Acharya SK, Mehta M, Chhabra S; Shalimar; Rana S, Das A, Dattagupta S, Dhiman RK, Chawla YK. High potency multistrain probiotic improves liver histology in non-alcoholic fatty liver disease (NAFLD): a randomised, double-blind, proof of concept study. BMJ Open Gastroenterol. 2019 Aug 7;6(1):e000315. doi: 10.1136/bmjgast-2019-000315. eCollection 2019.
PubMed 31423319
Dong TS, Jacobs JP. Nonalcoholic fatty liver disease and the gut microbiome: Are bacteria responsible for fatty liver? Exp Biol Med (Maywood). 2019 Apr;244(6):408-418. doi: 10.1177/1535370219836739. Epub 2019 Mar 14.
PubMed 30871368
Khan A, Ding Z, Ishaq M, Bacha AS, Khan I, Hanif A, Li W, Guo X. Understanding the Effects of Gut Microbiota Dysbiosis on Nonalcoholic Fatty Liver Disease and the Possible Probiotics Role: Recent Updates. Int J Biol Sci. 2021 Feb 8;17(3):818-833. doi: 10.7150/ijbs.56214. eCollection 2021.
PubMed 33767591
Bozic D, Podrug K, Mikolasevic I, Grgurevic I. Ultrasound Methods for the Assessment of Liver Steatosis: A Critical Appraisal. Diagnostics (Basel). 2022 Sep 22;12(10):2287. doi: 10.3390/diagnostics12102287.
PubMed 36291976
Merriman RB, Ferrell LD, Patti MG, Weston SR, Pabst MS, Aouizerat BE, Bass NM. Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease. Hepatology. 2006 Oct;44(4):874-80. doi: 10.1002/hep.21346.
PubMed 17006934
Sanyal AJ, Williams SA, Lavine JE, Neuschwander-Tetri BA, Alexander L, Ostroff R, Biegel H, Kowdley KV, Chalasani N, Dasarathy S, Diehl AM, Loomba R, Hameed B, Behling C, Kleiner DE, Karpen SJ, Williams J, Jia Y, Yates KP, Tonascia J. Defining the serum proteomic signature of hepatic steatosis, inflammation, ballooning and fibrosis in non-alcoholic fatty liver disease. J Hepatol. 2023 Apr;78(4):693-703. doi: 10.1016/j.jhep.2022.11.029. Epub 2022 Dec 14.
PubMed 36528237
Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016 Aug;65(8):1038-48. doi: 10.1016/j.metabol.2015.12.012. Epub 2016 Jan 4.
PubMed 26823198
Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, Kleiner DE, Loomba R. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023 May 1;77(5):1797-1835. doi: 10.1097/HEP.0000000000000323. Epub 2023 Mar 17. No abstract available.
PubMed 36727674
Kobyliak N, Abenavoli L, Mykhalchyshyn G, Kononenko L, Boccuto L, Kyriienko D, Dynnyk O. A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial. J Gastrointestin Liver Dis. 2018 Mar;27(1):41-49. doi: 10.15403/jgld.2014.1121.271.kby.
PubMed 29557414

Interested in taking part?

Eva Cubric, doctor of medicine

+38522641465

gastroenterologija@bolnica-sibenik.hr

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
Active, not recruitingPhase 1/2
A Study to Evaluate ALN-CIDEB in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease or With Metabolic Dysfunction-Associated Steatohepatitis (MASLD/MASH)
Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Dysfunction-Associated Steatohepatitis
Recruiting
Exercise for an Aging Liver (EXALIVER)
MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease, MASH - Metabolic Dysfunction-Associated Steatohepatitis
RecruitingPhase 2
Study to Evaluate ALN-CIDEB in Adults With Fibrotic Metabolic Dysfunction-Associated Steatohepatitis (MASH)
Metabolic Dysfunction-Associated Steatohepatitis (MASH)
RecruitingPhase 3
A Study Evaluating the Efficacy and Safety of Pegozafermin in Participants With MASH and Fibrosis (ENLIGHTEN-Fibrosis)
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASH) / Nonalcoholic Steatohepatitis (NASH) With Fibrosis

All MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis) trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Sinbiotic With Multispecies Probiotics on Liver Parameters in Patients With Metabolic Associated Steatotic Liver Disease
ClinicalTrials.gov ID: NCT07025980
Acronym / sponsor ID: 01-22682/1-23
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
Phase: Phase 2
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 114 participants (estimated)
Lead sponsor: Eva CubricUniversity, hospital or other
Collaborators: General Hospital Šibenik, Croatia, General Hospital Zadar, University Hospital Dubrava, University Hospital Rijeka, Clinical Hospital Merkur, University Hospital Sestre Milosrdnice, University Hospital of Split
Study start: 1 Jul 2025 (estimated)
Primary completion: 31 Jul 2028 (estimated)
Study completion: 31 Jul 2029 (estimated)
First posted: 18 Jun 2025 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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:

Participants will:

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
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).

Arm	Type	Receives
test group	Experimental	Dietary Supplement: The test product is a ready-to-use sinbiotic preparation of multispecies probiotics, ca-butyrate and FOSTest 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.
Placebo	Placebo comparator	Dietary Supplement: Placebo DrugPlacebo 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.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (7 listed)

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),

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
The test product is a ready-to-use sinbiotic preparation of multispecies probiotics, ca-butyrate and FOSThe 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.	Dietary supplement	test group
Placebo DrugContains 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.	Dietary supplement	Placebo

Primary outcome

change in the controlled attenuated coefficient CAP (dB/m/MHZ) for steatosis
Time frame: at baseline and after 270 days of intervention*
change in liver stiffness measurement (LSM) (kPa) measured by transient elastography for fibrosis
Time frame: at baseline and after 270 days of intervention
(1st and 2nd measured on FibroScan device, manufacturer Echosens, Paris, France)

12 secondary outcomes

change in serum levels of aspartate aminotransferase AST (U/L), alanine transferase ALT (U/L), gamma-glutamyl transferase GGT (U/L), ferritin (ng/ml)
Time frame: at baseline and after 270 days
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)
Time frame: at baseline and after 270 days
change in serum levels of cholesterol (mmol/L), triglycerides (mmol/L), HDL-cholesterol (mmol/L) and LDL-cholesterol (mmol/L)
Time frame: at baseline and after 270 days
change in waist circumference (cm) and body mass index (BMI=body weight (kg)/body height2(m)), kg/m2)
Time frame: at baseline and after 270 days
change in blood pressure (mmHg) measured by standard method
Time frame: at baseline and after 270 days
change in human Leucin-rich alpha-2-gylcoprotein 1 (LRG1) (ng/ml)
Time frame: at baseline and after 270 days
change in fecal calprotectin (ug/g)
Time frame: at baseline and after 270 days
change in controlled attenuated coefficient ATT (dB/cm/MHZ) for steatosis
Time frame: at baseline and after 270 days of intervention*
change in liver stiffness (Elastography) E (kPa) measured by 2D SWE for fibrosis
Time frame: at baseline and after 270 days of intervention
change in cardiovascular risk according to the European Society of Cardiology SCORE-2 tables
Time frame: at baseline and after 270 days
change in quality of life according to the validated WHO SF-36 Quality of Life Questionnaire
Time frame: at baseline and after 270 days
change in serum adiponectin levels (ng/ml)
Time frame: at baseline and after 270 days (only on Sibenik patients)

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2025.
Background: PubMed 32613718Lukenda Zanko V, Domislovic V, Trkulja V, Krznaric-Zrnic I, Turk-Wensveen T, Krznaric Z, Filipec Kanizaj T, Radic-Kristo D, Bilic-Zulle L, Orlic L, Dinjar-Kujundzic P, Poropat G, Stimac D, Hauser G, Mikolasevic I. Vitamin D for treatment of non-alcoholic fatty liver disease detected by transient elastography: A randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2020 Nov;22(11):2097-2106. doi: 10.1111/dom.14129. Epub 2020 Aug 5.
Background: PubMed 39125336Fogacci F, Giovannini M, Di Micoli V, Grandi E, Borghi C, Cicero AFG. Effect of Supplementation of a Butyrate-Based Formula in Individuals with Liver Steatosis and Metabolic Syndrome: A Randomized Double-Blind Placebo-Controlled Clinical Trial. Nutrients. 2024 Jul 28;16(15):2454. doi: 10.3390/nu16152454.
Background: PubMed 37771001Silva RSD, Mendonca IP, Paiva IHR, Souza JRB, Peixoto CA. Fructooligosaccharides and galactooligosaccharides improve hepatic steatosis via gut microbiota-brain axis modulation. Int J Food Sci Nutr. 2023 Nov;74(7):760-780. doi: 10.1080/09637486.2023.2262779. Epub 2023 Nov 15.
Background: PubMed 31423319Duseja A, Acharya SK, Mehta M, Chhabra S; Shalimar; Rana S, Das A, Dattagupta S, Dhiman RK, Chawla YK. High potency multistrain probiotic improves liver histology in non-alcoholic fatty liver disease (NAFLD): a randomised, double-blind, proof of concept study. BMJ Open Gastroenterol. 2019 Aug 7;6(1):e000315. doi: 10.1136/bmjgast-2019-000315. eCollection 2019.
Background: PubMed 30871368Dong TS, Jacobs JP. Nonalcoholic fatty liver disease and the gut microbiome: Are bacteria responsible for fatty liver? Exp Biol Med (Maywood). 2019 Apr;244(6):408-418. doi: 10.1177/1535370219836739. Epub 2019 Mar 14.
Background: PubMed 33767591Khan A, Ding Z, Ishaq M, Bacha AS, Khan I, Hanif A, Li W, Guo X. Understanding the Effects of Gut Microbiota Dysbiosis on Nonalcoholic Fatty Liver Disease and the Possible Probiotics Role: Recent Updates. Int J Biol Sci. 2021 Feb 8;17(3):818-833. doi: 10.7150/ijbs.56214. eCollection 2021.
Background: PubMed 36291976Bozic D, Podrug K, Mikolasevic I, Grgurevic I. Ultrasound Methods for the Assessment of Liver Steatosis: A Critical Appraisal. Diagnostics (Basel). 2022 Sep 22;12(10):2287. doi: 10.3390/diagnostics12102287.
Background: PubMed 17006934Merriman RB, Ferrell LD, Patti MG, Weston SR, Pabst MS, Aouizerat BE, Bass NM. Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease. Hepatology. 2006 Oct;44(4):874-80. doi: 10.1002/hep.21346.
Background: PubMed 36528237Sanyal AJ, Williams SA, Lavine JE, Neuschwander-Tetri BA, Alexander L, Ostroff R, Biegel H, Kowdley KV, Chalasani N, Dasarathy S, Diehl AM, Loomba R, Hameed B, Behling C, Kleiner DE, Karpen SJ, Williams J, Jia Y, Yates KP, Tonascia J. Defining the serum proteomic signature of hepatic steatosis, inflammation, ballooning and fibrosis in non-alcoholic fatty liver disease. J Hepatol. 2023 Apr;78(4):693-703. doi: 10.1016/j.jhep.2022.11.029. Epub 2022 Dec 14.
Background: PubMed 26823198Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016 Aug;65(8):1038-48. doi: 10.1016/j.metabol.2015.12.012. Epub 2016 Jan 4.
Background: PubMed 36727674Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, Kleiner DE, Loomba R. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023 May 1;77(5):1797-1835. doi: 10.1097/HEP.0000000000000323. Epub 2023 Mar 17. No abstract available.
Results publication: PubMed 29557414Kobyliak N, Abenavoli L, Mykhalchyshyn G, Kononenko L, Boccuto L, Kyriienko D, Dynnyk O. A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial. J Gastrointestin Liver Dis. 2018 Mar;27(1):41-49. doi: 10.15403/jgld.2014.1121.271.kby.
Individual participant dataSharing planned: No. It will not be shared in public, but by the individual request, and only after the approval of each institution in collaboration (as Ethics Commities of each institution has demand)

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Eva Cubric, doctor of medicine contact

+38522641465

gastroenterologija@bolnica-sibenik.hr

Marko Skelin, doctor of science, magh.pharm contact

+38522641641

marko.skelin@uniri.hr

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

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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 18 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Eva Cubric, doctor of medicine (+38522641465, gastroenterologija@bolnica-sibenik.hr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

change in the controlled attenuated coefficient CAP (dB/m/MHZ) for steatosis (time frame: at baseline and after 270 days of intervention*). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07025980, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2025.