Clinical Trial of Limonene on Regulating Metabolism-related Fatty Liver Disease (MAFLD) and Analysis of TCM Constitution
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Difference of controlled attenuation parameter (CAP) in liver fat
研究概览
简要总结
The prevention and treatment of metabolic-related fatty liver disease (MAFLD) involves many fields in preventive medicine and clinical medicine. So far, western medicine has not yet completed the elucidation of the mechanism of this type of disease, and there is a lack of effective therapeutic drugs.The purpose of this study was to evaluate the effectiveness and safety of limonene capsules (marketed product in China) in the treatment of metabolic-related fatty liver disease and related lipid-lowering mechanisms.
详细描述
In April 2020, in the famous journal "Journal of Hepatology" in the field of liver disease, an internationally renowned liver disease expert group jointly proposed to replace non-alcoholic fatty liver disease (NAFLD) with metabolic associated fatty liver disease (MAFLD) . The concept of non-alcoholic fatty liver disease (NAFLD) was first proposed by Ludwig in 1980. It specifically refers to the excessive deposition of liver fat without excessive drinking. It is a type of liver that is closely related to insulin resistance and genetic susceptibility. Non-alcoholic fatty liver disease (NAFLD) is China country's largest chronic liver disease and the primary cause of abnormal liver enzymes in health examinations. It can lead to liver disability and death. It is also closely related to a variety of metabolic diseases and the high incidence of colorectal tumors. Western medicine has not yet fully elucidated its mechanism, and no drugs have been officially approved for the clinical treatment of NAFLD.
The new MAFLD nomenclature highlights the central role of metabolic factors in causing liver fat deposition in this type of liver disease. Traditional Chinese medicine believes that the abnormal accumulation of fat in the liver of such fatty liver patients is a pathological product of the microscopic loss of water and valley essence. It belongs to phlegm stasis, which blocks the liver collaterals. It coincides with the core of the metabolic etiology of recent liver disease experts.
Limonene is widely found in the essential oils of traditional Chinese medicine tangerine peel, green peel and other plants. Its taste is sour, sweet and pungent.It is returned to the liver and gallbladder meridian. It has an aromatic odor effect.
A large number of animal and cell experiments in the early stage have shown that limonene can inhibit the differentiation of adipocytes (pre-adipocytes) and promote the apoptosis of mature adipocytes, which is related to the inhibition of fatty acid synthesis. Toxicity load experiments show that limonene has very low toxicity. The accumulation of lipids in the liver of mice has a regulatory effect with significantly reducing the content of liver cholesterol and triglycerides, and also has a certain effect on lipid metabolism disorders, hyperglycemia and other metabolic syndromes. It can alleviate the effects of high-fat diet and N- Efficacy of nitro-L-arginine methyl ester-induced resistance to non-alcoholic fatty liver in rats. The main indication of limonene capsules (marketed product in China) is liver and gallbladder diseases. Traditional Chinese medicine believes that liver and gallbladder are related to each other. This comprehensively shows that limonene capsules are promising to be developed as a pure Chinese medicine product for the safe and effective treatment of MAFLD.
However, there has been no clinical evaluation of the clinical efficacy of limonene in the treatment of metabolic-related fatty liver disease. As a typical aromatic Chinese medicine, the mechanism of limonene in the treatment of fatty liver urgently needs to be revealed by modern medicine and molecular biology techniques.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
double blinded
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis and imaging diagnosis of MAFLD and BMI index greater than or equal to 23kg/m2；
- •The age of the recruiter is between 18-65 years old;
- •Those who can cooperate with various treatments and data measurements according to the treatment cycle, and can persist in completing the test;
- •Those who accept and are willing to sign the informed consent.
排除标准
- •Potential recruiters who meet the inclusion criteria will be excluded if they meet any of the following:
- •Those who routinely take prescription drugs (except regular contraceptive drugs) or those who use auxiliary Chinese and Western drugs to treat non-alcoholic fatty liver;
- •Patients suffering from viral hepatitis, autoimmune hepatitis, hepatolenticular degeneration, hypothyroidism, infection, and biliary tract diseases that lead to abnormal liver function;
- •Patients who have taken the following drugs in the past 4 weeks: hypoglycemic drugs, lipid-lowering drugs (such as statins, fibrates, etc.) and drugs that may affect liver fat content (such as: silybin, ursodeoxycholic acid) , Bicyclic alcohol, phosphatidylcholine and vitamin E, glucocorticoid);
- •Patients with diabetes or those who have undergone bariatric surgery;
- •People who have gained or lost weight by 10 kg or more in the past two months;
- •People who are allergic to limonene capsules; or people who are allergic to citrus foods; people who especially like to eat a lot of citrus foods (daily dosage more than 100 grams);
- •Patients with severe cardiac insufficiency and malignant tumors;
- •Patients who have a history of mental illness and cannot cooperate with this project;
- •Pregnant and lactating women, or women or men who are willing to become pregnant or give birth during the study;
- •Participate in any other clinical trials;
- •Other situations where the researcher thinks it is inappropriate to participate in this research.
研究组 & 干预措施
Limonene capsules(marketed product in China)
Limonene capsules(marketed product in China) donate by pharmaceutical company
干预措施: Limonene capsule (Drug)
Limonene capsules(Placebo)
Same smell, color and shape as limonene capsules(marketed product in China), without limonene in capsules
干预措施: Limonene capsules(Placebo) (Drug)
结局指标
主要结局
Difference of controlled attenuation parameter (CAP) in liver fat
时间窗: at baseline and twelve weeks after administration
Changes in controlled attenuation parameter (CAP) in liver fat measured with transient elastography between the drug group and the placebo group.
Difference of rate of BMI index
时间窗: at baseline, four, twelve weeks after administration
The percent change of BMI index between the drug group and the placebo group.
次要结局
- Difference of aspartate transaminase (AST) index(at baseline, four, twelve weeks after administration)
- Difference of total cholesterol (TC) index(at baseline, twelve weeks after administration)
- Difference of glycated hemoglobin（GHb）index(at baseline, twelve weeks after administration)
- Difference of the Traditional Chinese of Medicine ( TCM ) Physique Questionnaire(at baseline, two，four，six，eight，ten weeks, twelve and sixteen weeks after administration)
- Difference of waist circumference(at baseline, four, twelve weeks after administration)
- Difference of alanine transaminase (ALT) index(at baseline, four, twelve weeks after administration)
- Difference of glycerin trilaurate (TG) index(at baseline, twelve weeks after administration)
- Difference of low-density lipoprotein cholesterol (LDL-C) index(at baseline, twelve weeks after administration)
- Difference of apolipoprotein E (ApoE) index(at baseline, twelve weeks after administration)
- Difference of blood sugar index(at baseline, twelve weeks after administration)
- Difference of the Short Form 36 physical component summary (SF-36 PCS) score(at baseline, two，four，six，eight，ten weeks, twelve and sixteen weeks after administration)
- Difference of the Chronic Liver Disease Questionnaire (CLDQ)(at baseline, two，four，six，eight，ten weeks, twelve and sixteen weeks after administration)
- Difference of glutamic transpeptidase (GGT) index(at baseline, four, twelve weeks after administration)
- Difference of insulin index(at baseline, twelve weeks after administration)
- Difference of high-density liptein cholesterol（HDL-C）index(at baseline, twelve weeks after administration)
研究者
Hongsheng Tan
Associate Professor
Shanghai Jiao Tong University School of Medicine