Oltipraz for Liver Fat Reduction in Patients With Non-alcoholic Fatty Liver Disease Except for Liver Cirrhosis

Dithiolethiones, a novel class of adenosine monophosphate-activated protein kinase (AMPK) activators, prevent insulin resistance through AMPK-dependent p70 ribosomal S6 kinase-1 (S6K1) inhibition. And it is well known that the modulation of S6K1 by oltipraz inhibited the development of insulin resistance and hyperglycemia through the AMPK-S6K1 pathway.Also some research reported that LXRg (a member of the nuclear hormone receptor)-mediated increases in SREBP-1c (the sterol regulatory element-binding protein-1c gene) promote the expression of lipogenic genes and enhance fatty acid synthesis and oltipraz inhibits LXRg and SREBP-c. Therefore, Oltipraz inhibits fatty acid synthesis through AMPK-S6K1 pathway and LXRg-SREBP-1c pathway in liver.

Inclusion criteria

• A person the ages of 19 and 75 years old
• Patients with non-alcoholic fatty liver disease other than cirrhosis that meets all of the following criteria:

• Abdominal ultrasonography of Screening indicates that the liver is brighter than the spleen or kidneys, causing suspected fatty liver
• Persons with liver fat content is 20% or more on the MRS
• Those who do not have significant alcohol intake within two years before screening (men: no more than 210 g per week; women: no more than 140 g per week)
• Those who with an alcohol use disorder identification test (AUDIT) result point is no more than 7, during screening.
• Persons with body mass index (BMI) more than 23 kg/m2 during screening
• A person who satisfies the following laboratory test results when screening

• Platelet ≥ 130,000/㎣
• White blood cell (WBC) ≥ 3,000/㎣
• Absolute neutrophil count (ANC) ≥ 1,500/㎣
• Albumin ≥ 3.5 g/dL
• Serum creatinine ≤ 1.5 X upper limit of normal (ULN)
• ULN < Alanine transaminase (ALT) or aspartate transaminase (AST) ≤ 250 IU/L
• A person who is willing to maintain the same lifestyle (exercise, alcohol intake, diet, etc.) maintained for at least four weeks before screening during the clinical trial period.
• A person who voluntarily agrees to participate in this clinical trial

Exclusion criteria

• A person who has history of following disease or surgery

• Malignant tumour with liver cancer
• Malignant tumor excluding liver cancer, However, registration is possible in the following cases

• If the investigator determines that the patient has been completely cured after maintaining the condition for at least five years
• In case of basal cell or squamous cell carcinoma of the skin, the patient is able to maintain a complete condition for more than three years in the case of cainoma in the cervix (CIN) and carcinema in situ (CIS), and other areas.
• autoimmune disease (e.g., inflammatory bowel disease, autoimmune hemolytic disease, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, rheumatoid arthritis, severe psoriasis, etc.)
• Bariatric surgery within 24 weeks before screening
• A Person who has comorbidity of the following diseases at the time of screening

• Liver cirrhosis identified by an epidemiological or histological examination
• Cumulative disease (e.g., alcohol liver disease, toxic hepatitis, autoimmune liver disease, metabolic liver disease, biliary closure, etc.) that may indicates liver abnormalities other than non-alcoholic fatty liver disease
• A Person who has been infected or has Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
• Type 1 diabetes or type 2 diabetes (hemoglobin A1c (HbA1c) > 9%)
• A person who has positive result of Human immunodeficiency virus antibody (HIV Ab).
• A persons with conditions that may affect the effectiveness and safety by investigator
• A person with AST/ALT ratio of more than 2 at screening
• The person who has the following medication history

• Persons administered vitamin E (≥ 800 IU/day) or thiazolidatedione drugs or glucagon-like peptide-1 (GLP-1) agonist drugs within 12 weeks prior to screening
• Persons who were given antiobestic drug within 12 weeks of screening For example; antiobestic drug with Central nervous system action: Amfepramone, bupropion and naltrexone, cathine, clobenzorex, dexfenfluramine, ephedrine combinations, etilamfetamine, fenfluramine, lorcaserin, mazindol, mefenorex, phentermine, sibutramine, Peripheral neurotic Obesity drugs: Orlistat, Rimonabant, etc
• A person who received medications that could cause fatty liver disease within 8 weeks prior to screening For example; Administration of systemic glucocorticoids for more than two weeks Anabolic steroid-based drug, Estrogen-based drug, Azole-based antimicrobial agent, Nucleoside, Nucleotide reverse transcriptase inhibitor-based drug, Tetracycline-based drug, Amiodarone, tamoxifen, methotrexate, valproic acid, etc
• A person who administered drugs that may affect the progress of non-alcoholic fatty liver disease within 4 weeks prior to screening or who require administration during clinical trials For example; Silymarin, biphenyl dimethyl dicarboxylate (DDB), ursodeoxycholic acid (UDCA), S-adenosyl-L-methionine (SAMe), betaine, pentoxyfylline, sodium-glucose cotransporter-2 (SGLT-2) inhibitor, omega 3 fatty acid, etc.

• However, the following drugs can be registered if they are under stable dosage for at least 12 weeks and are expected to remain unchanged during clinical trials; Sulfonylurea-based drug, metformin, insulin, dipeptidyl peptidase-4 inhibitor (DPP-4 inhibitor), a-glucosidase inhibitor (a-GI), meglitinide-based drug, statin-based drug, fibrate-based drug, nicotinic acid, ezetimibe, beta-blockers based drug, thiazide based drug
• A person who receive non-drug treatment that may affect the liver within 4 weeks prior to screening.
• A person who administered/treated with other clinical trials/medical devices within 4 weeks prior to screening
• Those who are not able to MRS(I)
• A female who is pregnant, may be pregnant, or is lactating
• A person who is not willing to use appropriate contraceptives during this clinical trial.
• A person who is hypersensitive to the Investigational Product
• A person who is deemed ineligible for clinical trials by the investigator