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

Официальное название

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

Обзор

The goal of this clinical trial is to evaluate whether a specific probiotic mixture can improve liver health in adults with moderate metabolic dysfunction-associated steatotic liver disease (MASLD). The main questions it aims to answer are: Can the probiotics improve liver fat and stiffness as measured by non-invasive imaging (FibroScan® CAP and FAST scores)? Does the probiotic affect other health markers like cholesterol, blood sugar, inflammation, and gut bacteria? Researchers will compare people taking the probiotic to those taking a placebo (a capsule with no active ingredients) to see if the probiotic has beneficial effects. Participants will: Be randomly assigned to take either the probiotic or placebo daily for 6 months. Attend 3 study visits (at the start, 3 months, and 6 months). Provide blood and stool samples. Undergo liver scans (FibroScan®). Complete a health and nutrition questionnaire. This study includes adults aged 18-65 with moderate MASLD and certain metabolic health conditions. Participants must not be pregnant, breastfeeding, or taking certain medications or supplements that could interfere with the study.

Вмешательства

• Пищевая добавка Lactiplantibacillus plantarum Probiotic Mixture
  A daily oral probiotic capsule containing three specific strains of Lactiplantibacillus plantarum (KABP011, KABP012, KABP013) 1,2 billion CFU with vitamin B1, designed to modulate gut microbiota and improve liver health in MASLD patients. It is compared to a placebo in a 6-month, double-blind, mechanistic trial.
• Пищевая добавка Placebo comparator containing maltodextrin
  Placebo comparator containing maltodextrin

Первичные конечные точки

• Changes in MASLD from baseline [Срок оценки: From enrollment to the end of treatment at 6 months.]

Вторичные конечные точки (12)

• Changes from baseline in Liver Fibrosis (kPa) [Срок оценки: From enrollment to the end of treatment at 6 months.]
• Changes form baseline in MASLD related index - FLI [Срок оценки: From enrollment to the end of treatment at 6 months.]
• Changes form baseline in MASLD related index - FIB-4 [Срок оценки: From enrollment to the end of treatment at 6 months.]
• Changes form baseline in MASLD related index - APRI [Срок оценки: From enrollment to the end of treatment at 6 months.]
• Changes from baseline in metabolic syndrome score (siMS) [Срок оценки: From enrollment to the end of treatment at 6 months.]
• Changes from baseline in weight (kg) [Срок оценки: From enrollment to the end of treatment at 6 months.]
• Changes from baseline in height (cm) [Срок оценки: From enrollment to the end of treatment at 6 months.]
• Changes from baseline in Body Mass Index (BMI) [Срок оценки: From enrollment to the end of treatment at 6 months.]
• Changes from baseline in waist circumference (cm) [Срок оценки: From enrollment to the end of treatment at 6 months.]
• Changes from baseline in hip circumference (cm) [Срок оценки: From enrollment to the end of treatment at 6 months.]
• Changes from baseline in waist/hip ratio [Срок оценки: From enrollment to the end of treatment at 6 months.]
• Changes from baseline in systolic and diastolic blood pressure. [Срок оценки: From entollment to the end of treatment at 6 months.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Испания · 1 центр

• Hospital Universitari Dr. Josep Trueta — Girona

Идентификаторы

NCT: NCT07193927 · AB-MASLD-25

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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