Effects of Probiotics (P. Pentosaceus, L. Lactis or L. Helveticus) in NASH

Study Overview
=================
Brief Summary
-----------------
A study for evaluating the improvement effect of non-alcoholic steatohepatitis (NASH) of probiotics

Detailed Description
-----------------
Non-alcoholic fatty liver disease progresses to fatty liver, hepatitis, cirrhosis, and liver cancer, resulting in a high mortality rate. The prevalence of non-alcoholic fatty liver disease at home and abroad is a major social and economic burden. However, there is no cure for non-alcoholic fatty liver disease. Recently, intestinal axis theory related to the development of chronic liver disease and microbial community has emerged. Intake of probiotics is known to play a role in regulating gut microflora. Improvement of non-alcoholic fatty liver disease can be expected through administration of probiotics.

Official Title
-----------------
Effects of Probiotics (P. Pentosaceus, L. Lactis or L. Helveticus) in Patients With Nonalcoholic Hepatitis

Conditions
-----------------
Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
-----------------
* Dietary Supplement: Probiotics


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Those who agreed to participate in this study and signed a written consent Adult men and women over 20 Patients diagnosed with non-alcoholic fatty liver ※ Exclusion criteria for alcoholic liver disease Those who have an alcoholic drinking ability of at least 60g per day for at least one year before visiting (30g for women) 1 bottle of shochu 360 ml * 20% = 72 g, 1 bottle of beer 500 ml (330 ml for commercial use) * 5% = 25 (16.5 g) Patients with higher liver numbers than normal ※ Adult normal liver level range by enzyme AST, ALT: 40 or less ALP: 20-130 GOT: 0-30, GPT: 0-38 GGT: 10-62 (male), 7-35 (female) Exclusion Criteria: Those who have consumed probiotics (lactic acid bacteria, etc.), prebiotics (dietary fiber, fructooligosaccharide, etc.), new biotics, fermented milk, etc. within the past month. Those who have continuously taken antibiotics within the last 2 months or who are likely to take them during the study period Those who have continuously consumed medicines or health functional foods that affect liver function within the past month. Those who have participated in other clinical trials within the past 1 month (but not applicable to medical device clinical trials) If you have any of the following Alcoholic liver disease, hereditary metabolic disease, autoimmune hepatitis systemic inflammatory disease or immune disease Hepatocellular carcinoma Uncontrolled cardiopulmonary disease Other serious systemic disorders in the heart, lungs, blood, and endocrine system A person with a history of malignancy diagnosis within the last 5 years Pregnant or lactating women Persons who have hypersensitivity to the test drug / placebo or components contained in the test drug / placebo or have severe allergic reactions Those who are not suitable for the clinical trial because the investigator judges

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 62 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Evaluates the effect of probiotic improvement on non-alcoholic fatty liver disease in patients diagnosed with non-alcoholic fatty liver disease.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotics group<br>The selected test subjects were randomly assigned to test group 1, test group 2, test group 3, or control group according to the order registered at visit 2 (week 0) after a 2-week run-in period, and for 8 weeks, the study drug or study After taking the treaty, analyze the results of the observations. | Dietary Supplement: Probiotics<br>* Experimental group Main ingredients: P. pentosaceus KID7, L. lactis CKDB001 or L. helveticus CKDB001 (containing 9 × 10^9 CFU / day) Control group Main ingredient: Crystalline cellulose<br>* Other names: Cellulose (Placebo);|
| Placebo Comparator: Placebo group<br>The selected test subjects were randomly assigned to test group 1, test group 2, test group 3, or control group according to the order registered at visit 2 (week 0) after a 2-week run-in period, and for 8 weeks, the study drug or study After taking the treaty, analyze the results of the observations. | Dietary Supplement: Probiotics<br>* Experimental group Main ingredients: P. pentosaceus KID7, L. lactis CKDB001 or L. helveticus CKDB001 (containing 9 × 10^9 CFU / day) Control group Main ingredient: Crystalline cellulose<br>* Other names: Cellulose (Placebo);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demographic characteristics | The gender, date of birth, age, menstruation, and amenorrhea, FAMILY HISTORY | 1 week | 
| Primary Outcomes; Liver Function Test | Primary outcomes of liver function enzyme level (AST, ALT, rGT, CHOL, ALP)[IU/L] | Baseline of AST, ALT, rGT, CHOL, and ALP at first week. | 
| Gut-Microbiome Composition | Change of the species and proportions of the gut microbiome. Proportion of phyrum level Composition of F/B ratio | Change from Baseline of fecal microbiome at 8 months | 
| Computed Tomography | change of the Abdominal ultrasonography or Computed Tomography(CT): Upper abdominal ultrasound or CT to determine the degree of fatty liver disease ② Fibroscan: Objectively and quantitatively grasp the degree of liver fibrosis by measuring the degree of firmness (elasticity) of the liver | Change from Baseline of CT image at 8 months | 
| change of BMI | Compare the body mass index. BMI=Body Weight/(Height)^2 | Change from Baseline BMI and weight at 6 months | 
| Secondary Outcomes; Liver Function Test | Secondary outcomes of liver function enzyme level (AST, ALT, rGT, CHOL, ALP)[IU/L] | Change from Baseline of AST, ALT, rGT, CHOL, and ALP at 8 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Probiotics, Liver disease, Gut microbiota