Focused Power Ultrasound Mediated Inferior Perirenal Adipose Tissue Modification Therapy for Non-Alcoholic Fatty Liver Disease: a Randomized Controlled Trial (PARADISE-NAFLD)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 3
- 主要终点
- Absolute Change in Liver Fat Content
研究概览
简要总结
This randomized, blinded, sham-control trial aims to evaluate the efficacy and safety of a novel focused power ultrasound mediated inferior perirenal adipose tissue modification therapy for non-alcoholic fatty liver disease.
详细描述
Visceral adiposity is closely related to the incidence of non-alcoholic fatty liver disease (NAFLD), and it is also directly associated with liver inflammation and fibrosis. Visceral adiposity, via its unique location and enhanced lipolytic activity, releases toxic free fatty acids, which are delivered in high concentrations directly to the liver and lead to the accumulation and storage of hepatic fat. Furthermore, it has been recognized as an important endocrine organ, and a variety of factors secreted by visceral adiposity may lead to an increased risk of NAFLD.
Peri-renal fat is a special type of visceral adiposity which is different from other type of visceral fat in histology, physiology, and functions. The position of peri-renal fat is more stable than other visceral fat. The investigators found that prophylactic perirenal adipose tissue ablation can prevent the development of NAFLD in mice induced by high fat diets, and also this novel focused power ultrasound can rapidly and efficiently promote the peri-renal adipose tissue fibrosis in the model of swine. Moreover, the investigators performed a single arm, small sample study to investigate the feasibility of the novel focused power ultrasound to modify the inferior peri-renal adipose tissue in NAFLD participants, showing that this kind of method was feasible and safe.
In this study, the investigators aim to further evaluate the efficacy and safety of a novel focused power ultrasound mediated inferior perirenal adipose tissue modification therapy for NAFLD.
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, Care Provider, Investigator)
盲法说明
The masking range includes participants, most researchers (including the study leader; subjects screening researchers; follow-up researchers; sonographers, MR scanners, members of the clinical endpoint identification committee, and etc.) except for the study statistical analysts and the therapy operators.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years or older at the time of screening.
- •Total liver fat content ≥10% measured by MRI-PDFF.
- •Body mass index (BMI) ≥ 25 kg/m^
- •The anteroposterior, transverse and axial diameters of inferior perirenal fat pad measured by ultrasound should be at least 20mm.
- •Participants should be willing to sign the informed consent form of the study.
排除标准
- •History of significant alcohol consumption (significant alcohol consumption was defined as more than 140 g/week in females and more than 210 g/week in males in the last 12months before screening, on average).
- •Secondary factors causing hepatic steatosis, including viral hepatitis C, autoimmune hepatitis, total parenteral nutrition, celiac disease, Wilson's disease, hypothyroidism, hereditary hemochromatosis, drug factors (amiodarone, glucocorticoids, methotrexate, tamoxifen), etc.
- •Complicating other chronic liver diseases, mainly including viral hepatitis, cholestatic liver disease, drug-induced liver injury, etc.
- •Weight change >10% in the past 3 months.
- •Clinical or pathological diagnosis of cirrhosis.
- •NAFLD treatment drugs (such as vitamin E, obecholic acid, thiazolidinediones, etc.) were used within 6 months before enrollment.
- •History of bariatric surgery.
- •History of kidney and/or surrounding tissue surgery.
- •Waist skin infection.
- •Urinary stones and/or hematuria (positive for gross hematuria or occult blood).
- •Unstable cardiovascular diseases: (1) Myocardial infarction, unstable angina pectoris or cerebrovascular accident occurred in the last 6 months. (2) Persistent atrial fibrillation without anticoagulation. (3) Severe structural heart disease (including valvular heart disease, cardiomyopathy). (4) second degree and above atrioventricular block and/or sick sinus syndrome. (5) Uncontrolled hypertension.
- •Type 1 diabetes or uncontrolled hyperglycemia (HBA1c ≥ 9.5%).
- •Participants with untreated tumors.
- •Laboratory screening results include one or more of the following: (1) Neutrophil absolute value <1.0x10^9/L. (2) Platelet count <100x10^9/L. (3) Hemoglobin <100g/L. (4) Albumin <35g/L. (5) International standard value >1.
- •(6) Total bilirubin >1.5 times the upper limit of normal value. (7) The estimated glomerular filtration rate was <60ml/ (minx1.73m^2).
- •Participants who are pregnant, breastfeeding or trying to conceive.
- •Any contraindication or inability to obtain an MRI.
- •Participants who were unable to follow up.
- •Any other situation that the investigator considers to be detrimental to the patient's health, hindering the completion of the study, or interfering with the results of the study.
结局指标
主要结局
Absolute Change in Liver Fat Content
时间窗: From baseline to 3 months post-procedure
Absolute change in liver fat content assessed by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) at 3-month compared with baseline
次要结局
- Relative Change in Liver Fat Content(From baseline to 3 months post-procedure)
- Proportion of MRI-PDFF Responders(From baseline to 3 months post-procedure)
- Change in Enhanced Liver Fibrosis Test(From baseline to 3 months post-procedure)
- Change in Alanine Aminotransferase (ALT)(From baseline to 3 months post-procedure)
- Change in Concentration of Cytokeratin-18(From baseline to 3 months post-procedure)
- Change in Liver Stiffness Measurement and Controlled Attenuation Parameter(From baseline to 3 months post-procedure)
研究者
Xiangqing Kong
Head of Cardiology
The First Affiliated Hospital with Nanjing Medical University