Clinical trial NCT05402449: To Evaluate the Beneficial Effect of Probiotics on NAFLD Patients and the Role of Gut Microbiota Modulation
Official title: To Evaluate the Clinical Efficacy of Probiotic in Patients With NAFLD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-Alcoholic Fatty Liver Disease
Keywords: Probiotic
Non-Alcoholic Fatty Liver Disease
gut microbiota
Lead sponsor: GenMont Biotech Incorporation
Sponsor class: INDUSTRY
Collaborators: name: Fu Jen Catholic University Hospital
First posted: 2022-06-02
Enrollment: 70
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Controlled Trail
Primary purpose: SUPPORTIVE_CARE

Brief summary: In this study, the improvement of the clinical status of early-stage non-alcoholic fatty liver disease (NAFLD) patients after the probiotic intervention will be assessed. And the mechanism of probiotics to prevent the progression of illness would be investigated. The chronic inflammation status, systemic oxidative stress, metabolism of carbohydrates and lipid, and gut microbiota of NAFLD patients will also be analyzed.

Detailed description: Uncontrolled NAFLD evolves in Non-Alcoholic SteatoHepatitis (NASH), cirrhosis and liver cancer. Early intervention to prevent the progression of illness of NAFLD is very important. From 2005 to 2018, 15 clinical trials concluded that multiple-strain probiotics significantly reduced the liver inflammation index and blood lipids in NAFLD patients. Many reports indicated that NAFLD-associated risk factors, such as chronic inflammation, oxidative stress, insulin resistance, dyslipidemia, and obesity are closely correlated with gut microbiota. Some substances (such as endotoxin and alcohol) produced by harmful gut bacteria caused the progression of the illness of NAFLD.

Three strains are Genmont® Normal Lactobacillus (GMNL) which were divided from natural environments, included Lactobacillus reuteri GMNL-263 (heat-killed) and GMNL-89 (alive) and Lactobacillus rhamnosus GMNL-74 ( alive). They are all isolated from the gastrointestinal tract of healthy Taiwanese and were known as common food material worldwide. The previous clinical research on probiotic consumption in type 2 Diabetes mellitus patients under normal drug treatment was conducted in Changhua Christian Hospital. Results showed that L. reuteri GMNL-263 was able to stabilize the weight and blood pressure of patients. L. reuteri GMNL-89 had a stable effect on glycated hemoglobin. There was no adverse reaction when probiotics combining with type 2 diabetes drugs. Meanwhile, L. rhamnosus GMNL-74 was observed to reduce weight gain in obese mice. In this clinical study, The anti-liver inflammation effect of consumption of Lactobacillus sachet in NAFLD patients will be demonstrated at baseline, 3 months and 6 months. In this clinical study, the anti-liver inflammation effect of consumption of Lactobacillus sachet in NAFLD patients will be demonstrated at baseline, 3 months and 6 months to understand the impact of the probiotics on NAFLD. Since the treatment of fatty liver should focus on controlling weight, blood sugar, and blood fat, the relevant clinical indexes will also be investigated.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Nonalcoholic fatty liver disease (NALFD) by ultrasound.
* The range of Alanine aminotransferase (ALT) blood test is 60-300 U/L

Exclusion Criteria:

* Alcoholic consumption (Female ≥ 10g/day or Male ≥ 20g/per)
* Patients with liver diseases, HBV(hepatitis B virus), HCV(hepatitis C virus), Primary Biliary Cholangitis.
* Autoimmune system disease
* Wilson's disease
* Hereditary hemochromatosis
* Patients with uncontrolled malignancy
* The subject had previously received weight reduction surgery
* Taking Antibiotics, probiotics, or any other drugs that affect NAFLD or glucose and lipid metabolism in past 2 months
* Pregnant or lactating female patients
* Patient who have severe allergy to soybeans or peanuts

Primary outcomes:
measure: Serum ALT (Alanine Aminotransferase) level at baseline
timeFrame: baseline
measure: Change from baseline in Serum ALT (Alanine Aminotransferase) level at 3-months
timeFrame: 3-months
measure: Change from baseline in Serum ALT (Alanine Aminotransferase) level at 6-months
timeFrame: 6-months
Secondary outcomes:
measure: Change from baseline in BMI (Body Mass index) at 3-months
timeFrame: 3-months
measure: Change from baseline in BMI (Body Mass index) at 6-months
timeFrame: 6-months
measure: Change from baseline in Waist and hip circumference at 3-months
timeFrame: 3-months
measure: Change from baseline in Waist and hip circumference at 6-months
timeFrame: 6-months
measure: Change from baseline in blood pressure at 3-months
timeFrame: 3-months
measure: Change from baseline in blood pressure at 6-months
timeFrame: 6-months
measure: Change from baseline in the progress of the non-alcoholic fatty liver disease at 3-months
timeFrame: 3-months
measure: Change from baseline in the progress of the non-alcoholic fatty liver disease at 6-months
timeFrame: 6-months
measure: Change from baseline in levels of AST(Aspartate Aminotransferase) at 3-months
timeFrame: 3-months
measure: Change from baseline in levels of AST(Aspartate Aminotransferase) at 6-months
timeFrame: 6-months
measure: Change from baseline in the level of γ-GT (γ-Glutamyl Transpeptidase) at 3-months
timeFrame: 3-months
measure: Change from baseline in the level of γ-GT (γ-Glutamyl Transpeptidase) at 6-months
timeFrame: 6-months
measure: Change from baseline in the level of BUN (Blood Urea Nitrogen) at 3-months
timeFrame: 3-months
measure: Change from baseline in the level of BUN (Blood Urea Nitrogen) at 6-months
timeFrame: 6-months
measure: Change from baseline in the level of CRE (Creatinine) at 3-months
timeFrame: 3-months
measure: Change from baseline in the level of CRE (Creatinine) at 6-months
timeFrame: 6-months
measure: Change from baseline in levels of FBS (Fasting Blood Sugar) at 3-months
timeFrame: 3-months
measure: Change from baseline in the level of FBS (Fasting Blood Sugar) at 6-months
timeFrame: 6-months
measure: Change from baseline in levels of HbA1c (Hemoglobin A1C) at 3-months
timeFrame: 3-months
measure: Change from baseline in levels of HbA1c (Hemoglobin A1C) at 6-months
timeFrame: 6-months
measure: Change from baseline in levels of serum insulin at baseline
timeFrame: 3-months
measure: Change from 3-months in levels of serum insulin at baseline
timeFrame: 6-months
measure: Change from Baseline in levels of HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) at 3-months
timeFrame: 3-months
measure: Change from baseline in levels of HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) at 6-months
timeFrame: 6-months
measure: Change from baseline in levels of TC (Total Cholesterol) at 3-months
timeFrame: 3-months
measure: Change from baseline in levels of TC (Total Cholesterol) at 6-months
timeFrame: 6-months
measure: Change from baseline in level of HDL (High density lipoprotein) at 3-months
timeFrame: 3-months
measure: Change from baseline in level of HDL (High density lipoprotein) at 6-months
timeFrame: 6-months
measure: Change from baseline in level of LDL (Low density lipoprotein) at 3-months
timeFrame: 3-months
measure: Change from baseline in level of LDL (Low density lipoprotein) at 6-months
timeFrame: 6-months
measure: Change from baseline in level of TG (Triglyceride) at 3-months
timeFrame: 3-months
measure: Change from baseline in level of TG (Triglyceride) at 6-months
timeFrame: 6-months
measure: Change from baseline in level of hs-CRP (high-sensitivity C-reactive protein) at 3-months
timeFrame: 3-months
measure: Change from baseline in level of hs-CRP (high-sensitivity C-reactive protein) at 6-months
timeFrame: 6-months
measure: Change from baseline in level of TNF-α (Tumor necrosis factor-α) at 3-months
timeFrame: 3-months
measure: Change from baseline in level of TNF-α (Tumor necrosis factor-α) at 6-months
timeFrame: 6-months
measure: Change from baseline in level of IL-1β (Interleukin-1 β) at 3-months
timeFrame: 3-months
measure: Change from baseline in level of IL-1β (Interleukin-1 β) at 6-months
timeFrame: 6-months
measure: Change from baseline in level of IL-6 (Interleukin-6) at 3-months
timeFrame: 3-months
measure: Change from baseline in level of IL-6 (Interleukin-6) at 6-months
timeFrame: 6-months
measure: Change from baseline in level of LPS (Lipopolysaccharides) at 3-months
timeFrame: 3-months
measure: Change from baseline in level of LPS (Lipopolysaccharides) at 6-months
timeFrame: 6-months
measure: Change from baseline in level of Leptin at 3-months
timeFrame: 3-months
measure: Change from baseline in level of Leptin at 6-months
timeFrame: 6-months
measure: Change from baseline in level of Adiponectin at 3-months
timeFrame: 3-months
measure: Change from baseline in level of Adiponectin at 6-months
timeFrame: 6-months
measure: Change from baseline in the level of SCFA (Short Chain Fatty Acids) at 6-months
timeFrame: 6-months
measure: Change from baseline in the level of TMAO (Trimethylamine N-oxide) at 6-months
timeFrame: 6-months
measure: Change from baseline in Self-questionnaire of Diet and lifestyle assessments at 6-months
timeFrame: 6-months
measure: Change from baseline in self-record of the International physical activity questionary (IPAQ) in physical assessment at 6-months
timeFrame: 6-months
measure: Change from baseline in gut microbiota at 6-months
timeFrame: 6-months
Other outcomes:
Locations:
city: New Taipei City
country: Taiwan
facility: Fu Jen Catholic University Hospital
Study officials:
affiliation: Fu Jen Catholic University Hospital
name: Chi-Yang Chang, PhD
role: PRINCIPAL_INVESTIGATOR
References: