Evaluate the Efficacy and Safety of LivPhcD Capsules in the NAFLD Subjects

Study Overview
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Brief Summary
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Non-alcoholic fatty liver disease (also called NAFLD) is a disease in which excessive fat accumulates in the liver of a patient without a history of alcohol abuse. Early-stage NAFLD does not usually cause any harm but nonalcoholic steatohepatitis (NASH) can lead to serious liver damage, including fibrosis or cirrhosis. Nearly 25% of the world's population is affected by NAFLD. There are no FDA-approved medications for the treatment of NAFLD currently and although lifestyle modifications with appropriate diet and exercise have been shown to be beneficial, this has been difficult to achieve and sustain for the majority of patients. LivPhcD™ capsule have shown hepatoprotective effects in both animal and human data. This study aims to investigate the effects of LivPhcD™ capsule in hepatocellular lipid content using Fibroscan.

Official Title
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Multi-center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of LivPhcD Capsules in the NAFLD Subjects

Conditions
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NAFLD

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: 2 cap.LivPhcD/per day
* Dietary Supplement: 4 cap.LivPhcD/per day
* Dietary Supplement: 6 cap.LivPhcD/per day


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between 20 and 75 years of age. Capable of giving written informed consent and able to effectively communicate with the investigator and study personnel. Has a body mass index (BMI) ≥20 kg/m^2 and ≤50 kg/m^2 and stable weight for the past 3 months CAP ≥ 238 db/m Fibro scan (transient elastography) F0 F3 Exclusion Criteria: Pregnant or breastfeeding or planning to become pregnant or unwilling to use an acceptable contraceptive method to avoid pregnancy during the study period Type 1 diabetes mellitus. History of other causes of chronic liver disease [autoimmune, primary biliary cirrhosis, HBV (HBsAg positive) and HCV, Wilson disease, alpha-1-antitrypsin deficiency, hemochromatosis etc. Use of medications that could induce steatosis, such as estrogen or other hormonal replacement therapy, amiodarone, methotrexate, tamoxifen, raloxifene, pharmacological doses of oral glucocorticoids (≥10 mg per day of prednisone or equivalent), or chloroquine. Use of vitamin E (doses ≥800 IU/dy) or pioglitazone or SGLT2 inhibitor or GLP-1 agonists any FDA-approved drug for NASH to be approved during the study. Has significant systemic or major illnesses other than liver disease, ex: recent events (≤6 months before study entry) of congestive heart failure, unstable coronary artery disease, serious COPD, renal failure and need hemodialysis, stroke, transient ischemic attack, or organ transplantation Known alcohol abuse or alcohol use disorder (>20 g/day for women; >30 g/day for men) Has the abnormal data including: fasting TG >400 mg/dL ; ALT or GGT>5.0 x ULN；Bilirubin >2 x ULN，unless due to an alternative etiology such as Gilbert's syndrome; INR ≥1.3; Albumin < LLN; Platelet <0.95x LLN Subjects with hemoglobin A1c (HbA1c) >8.5% within 3 months before study entry Plan to have major surgery during the study period (bariatric surgery, biliary diversion surgery) Participation in any other investigational clinical trial within 30 days of entry to this protocol; History of HIV

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo without active ingredient | Dietary Supplement: Placebo<br>* Placebo matching LivPhcD cap.<br>|
| Active Comparator: 2 cap.LivPhcD/per day<br>515mg/LivPhcD cap. 2 cap./per day | Dietary Supplement: 2 cap.LivPhcD/per day<br>* 2 caps. LivPhcD cap. after meal, once a day<br>|
| Active Comparator: 4 cap.LivPhcD/per day<br>515mg/LivPhcD cap. 4 cap./per day, BID | Dietary Supplement: 4 cap.LivPhcD/per day<br>* 4 caps. LivPhcD cap. after meal, BID<br>|
| Active Comparator: 6 cap.LivPhcD/per day<br>515mg/LivPhcD cap. 6 cap./per day, TID | Dietary Supplement: 6 cap.LivPhcD/per day<br>* 6 caps. LivPhcD cap. after meal, TID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of Liver Fat | Between group difference in the proportion of patients with ≥ 10% reduction of baseline of liver fat by CAP(Controlled Attenuation Parameter) | 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in liver fat at least 30% reduction | Between group difference in the proportion of patients with ≥ 30% reduction of baseline of liver fat by CAP | 24 weeks and 36 weeks | 
| Change in liver fat at least 1 stage reduction | Between group difference in the proportion of patients with 1 stage reduction of baseline of liver fat by CAP | 24 weeks and 36 weeks | 
| Change in liver fat | Between group difference in mean change of liver fat by CAP | 24 weeks and 36 weeks | 
| Stable in liver fat | Between group difference in the proportion of patients with stable of baseline of liver fat by CAP | 24 weeks and 36 weeks | 
| Change in liver fibrosis at least 10% reduction | Between group difference in the proportion of patients with ≥ 10% reduction of baseline of liver fibrosis by Fibroscan | 24 weeks and 36 weeks | 
| Change in liver fibrosis at least 1 stage reduction | Between group difference in the proportion of patients with 1 stage reduction of baseline of liver fibrosis by Fibroscan | 24 weeks and 36 weeks | 
| Stable in liver fibrosis | Between group difference in the proportion of patients with stable reduction of baseline of liver fibrosis by Fibroscan | 24 weeks and 36 weeks | 
| Change in liver fibrosis | Between group difference in mean change of FIB-4 | 24 weeks and 36 weeks | 
| Change in ALT | Between group difference in mean change or in the proportion of patients of ALT | 24 weeks and 36 weeks | 
| Change in AST | Between group difference in mean change or in the proportion of patients of AST | 24 weeks and 36 weeks | 
| Change in GGT | Between group difference in mean change or in the proportion of patients of GGT | 24 weeks and 36 weeks | 
| Change in AP | Between group difference in mean change or in the proportion of patients of AP | 24 weeks and 36 weeks | 
| Change in Bilirubin | Between group difference in mean change or in the proportion of patients of Bilirubin | 24 weeks and 36 weeks | 
| Change in Triglyceride | Between group difference in mean change or in the proportion of patients of Triglyceride | 24 weeks and 36 weeks | 
| Change in Total Cholesterol | Between group difference in mean change or in the proportion of patients of Total Cholesterol | 24 weeks and 36 weeks | 
| Change in HDL-C | Between group difference in mean change or in the proportion of patients of HDL-C | 24 weeks and 36 weeks | 
| Change in LDL-C | Between group difference in mean change or in the proportion of patients of LDL-C | 24 weeks and 36 weeks | 
| Change in TNF-α | Between group difference in mean change or in the proportion of patients of TNF-α | 24 weeks and 36 weeks | 
| Change in C-Reactive Protein | Between group difference in mean change or in the proportion of patients of C-Reactive Protein | 24 weeks and 36 weeks | 
| Change in Albumin | Between group difference in mean change or in the proportion of patients of Albumin | 24 weeks and 36 weeks | 
| Occurrence of adverse events and serious adverse events | Between group difference in the occurrence of adverse events and serious adverse events. | 24 weeks and 36 weeks |