NCT04142749已完成3 期
A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Oltipraz
PharmaKing21 个研究点 分布在 1 个国家目标入组 146 人开始时间: 2019年11月15日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 146
- 试验地点
- 21
- 主要终点
- Variation of liver fat assessed
研究概览
简要总结
Oltipraz inhibits fatty acid synthesis through AMPK-S6K1 pathway and LXRg-SREBP-1c pathway in liver.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 19 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Oltipraz
Active Comparator
Oltipraz 30mg
干预措施: Oltipraz (Drug)
Placebo
Placebo Comparator
Placebo 30mg
干预措施: Placebos (Drug)
结局指标
主要结局
Variation of liver fat assessed
时间窗: 24 weeks compared to the baseline
Variation of liver fat assessed by MRS at 24 weeks compared to the baseline (%)
次要结局
- The variation in the amount of liver fat(24 weeks compared to the baseline)
- Variation of liver fat certificate grade(24 weeks compared to the baseline)
- Variation of NFS variation(24 weeks compared to the baseline)
- Variation of liver elasticities and fatty acids(24 weeks compared to the baseline)
- FIB-4(8 weeks, 16 weeks and 24 weeks)
- BMI(8 weeks, 16 weeks and 24 weeks)
- Variation of ALT, AST, γ-glutamyl transferase (GGT)(8 weeks, 16 weeks and 24 weeks)
- Cholesterol (total, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), triglyceride (TG)(8 weeks, 16 weeks and 24 weeks)
- Variation of Homeostatic model adjustment-insulin resistance (HOMA-IR) index(24 weeks compared to the baseline)
- Waist circumference(24 weeks compared to the baseline)
研究者
研究点 (21)
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