Daily probiotic mix for moderate MASLD in adults with overweight

Investigation of the Efficacy of a Probiotic Mixture in Subjects With Moderate Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Mechanistic Trial

This will see if taking a daily Lactiplantibacillus plantarum probiotic mix for 6 months can reduce liver fat and stiffness in adults 18–75 with moderate MASLD and BMI 25–42.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: AB Biotics, SA (industry)
• Locations: 1 site (Girona, Girona)
• Trial ID: NCT07193927 on ClinicalTrials.gov

What this trial studies

This is a randomized, placebo-controlled Phase 2 trial where participants are assigned to a probiotic capsule or a placebo daily for six months. Liver fat and stiffness will be tracked with FibroScan® CAP and FAST scores at baseline, 3 months, and 6 months, and blood and stool samples will be collected to measure lipids, glucose, inflammation, and gut microbiota changes. The trial focuses on adults with moderate MASLD, elevated ALT, and features of metabolic syndrome, with stable weight and medications prior to enrollment. The goal is to link changes in imaging-based liver measures with metabolic and microbiome markers to understand potential mechanisms of benefit.

Who should consider this trial

Good fit: Adults aged 18–75 with BMI 25–42 kg/m2, diagnosed moderate MASLD with FibroScan® CAP > 268 dB/m, elevated ALT (males >30 U/L, females >19 U/L), and at least three metabolic syndrome features who have had stable weight and medications before enrollment are the ideal candidates.

Not a fit: People without MASLD, with CAP below the threshold, with normal ALT, with unstable weight or recent medication changes, or with more advanced/other causes of liver disease are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, the probiotic could lower liver fat and stiffness and improve related metabolic markers like cholesterol, blood sugar, and inflammation.

How similar studies have performed: Previous small trials of probiotics in NAFLD/MASLD have shown mixed but sometimes favorable effects on liver enzymes and steatosis, so this approach has some prior, though not definitive, supporting evidence.

Eligibility criteria

Inclusion Criteria:

* Patients aged from 18 to 75 years old
* BMI 25 - 42kg/m2
* Diagnosed with MASLD and CAP value \> 268 dB/m evaluated by FibroScan®
* High ALT levels (\>30 U/L in males and \>19 U/L in females)
* Having at least three of the following features compatible with metabolic syndrome:

  i. Waist circumference ≥ 102 cm in males and ≥ 88 cm in females. ii. Fasting serum glucose (≥ 5.6 mmol/L or 100 mg/dl). iii. Glycated haemoglobin (HbA1c ≥ 5.7%/ 39 mmol/L). iv. Diagnosed or treated for type 2 diabetes. v. High blood pressure (≥ 130/85 mmHg). vi. High plasma triglycerides (≥ 1.70 mmol/L or 150 mg/dl). vii. Lower plasma of High-Density Lipoprotein (HDL cholesterol) (≤ 1.0 mmol/L or 40 mg/dl for males and ≤ 1.3 mmol/L or 50 mg/dl for females).
* Stable weight in the last 3 months (less than ± 4% weight variation).
* Stable medication or intake of food supplements for a medical condition that can affect study outcomes according to the Investigator's judgement in the last three months prior to study entry (bile salt sequestrants are not permitted).
* Not planning to change their dietary and lifestyle habits during the study.
* Willing and able to provide informed consent and comply with study procedures.

Exclusion Criteria:

* Fibrosis scores equal or higher than F2 (≥ 8.0 kPa).
* History of acute or chronic hepatitis A, B or C, autoimmune hepatitis, drug-induced liver diseases, severe liver diseases.
* Prior or pending liver transplantation.

Patients with at least one of the following concurrent conditions:

i. Type I diabetes ii. Uncontrolled type II diabetes (HbA1c \>8%) iii. Hypertriglyceridemia \> 350mg/dl iv. Human Immunodeficiency Virus (HIV) infection v. Diagnosis of hemochromatosis

* Current use of pioglitazone, SGLT-2 inhibitors, or approved drugs for MASLD or steatohepatitis within 8 weeks.
* Current use of bile salt sequestrants within 8 weeks.
* Significant gastrointestinal disease, such as inframmatory bowel disease (IBD, short bowel syndrome, chronic or recurrent diarrhoea, coeliac condition.
* Pancreatic failure, biliary dysfunction (including cholecystectomy and blood bilirubin abnormalities)
* Thyroid dysfunction, as assessed by the investigator (clinical criteria)
* History of:

  i. Cardiovascular disease (ischemic heart disease, heart failure, cerebrovascular disease, periphreal vascular disease).

ii. Cancer or immunosuppression. iii. Gastrointestinal surgery in the previous year (with the exception of appendicitis).

* Patients with a history of chronic alcohol or drug abuse: \> 14 units/week for females and \> 21 units/week for male
* Chronic and heavy smoking (\>20 cigarettes a day)
* Regular intake (\> 3 days/week) of other probiotics (including food complements or diary foods with other probiotic strains, e.g. Activia®, Actimel® or similar).
* Intake of nutraceuticals with an effect on hepatic function such as \> 500 mg/day omega-3 fatty acids, high-dose vitamin E supplements or milk thistle (sylibum marianum) extract ot their active ingredients (silymarin, silybin) regularly (\> 7 days) in the 15 days before study entry.
* Current use of systemic corticosteroids, androgens, clopidogrel, digoxin, acenocoumarol, warfarin, phenytoin, topiramate, lithium, tricyclic antidepressants, MAOIs or second-generation antipsychotics, amiodarone, tamixofen and/or diltiazem.
* History of use (\> 3 days) of oral or parenteral antibiotics one month before the study initiation.
* Chronic use of laxatives.
* Debilitating illnesses (advanced liver or kidney disease, severe depression, psychotic symptoms, neurological diseases).
* Current pregnancy (positive urine test) or planning to become pregnant during the study.
* Breastfeeding at the time of eligibility assessment.
* Patients who have participated in a clinical trial in the six-month period before the study.

Where this trial is running

Girona, Girona

• Hospital Universitari Dr. Josep Trueta — Girona, Girona, Spain (RECRUITING)

Study contacts

• Study coordinator: José Manuel Dr. Fernández-Real, PhD

Conditions: MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease, Fatty Liver Disease, Nonalcoholic, Overweight (BMI &gt, 25)