Clinical trial NCT06225713: Focused Power Ultrasound Mediated Inferior Perirenal Adipose Tissue Modification Therapy for Non-Alcoholic Fatty Liver Disease (PARADISE-NAFLD)
Official title: Focused Power Ultrasound Mediated Inferior Perirenal Adipose Tissue Modification Therapy for Non-Alcoholic Fatty Liver Disease: a Randomized Controlled Trial (PARADISE-NAFLD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Non-alcoholic Fatty Liver Disease
Keywords: Non-alcoholic Fatty Liver Disease
Focused ultrasound
Novel method
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: The Affiliated Jiangning Hospital of Nanjing Medical University
name: Suzhou Municipal Hospital
First posted: 2024-01-26
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, blinded, and sham-control study. The ratio of the intervention group versus sham-control group is 1:1
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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\^2.
* 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.

Exclusion Criteria:

* 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 \>1.5. (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.

Primary outcomes:
measure: Absolute Change in Liver Fat Content
timeFrame: From baseline to 3 months post-procedure
Secondary outcomes:
measure: Relative Change in Liver Fat Content
timeFrame: From baseline to 3 months post-procedure
measure: Proportion of MRI-PDFF Responders
timeFrame: From baseline to 3 months post-procedure
measure: Change in Alanine Aminotransferase (ALT)
timeFrame: From baseline to 3 months post-procedure
measure: Change in Concentration of Cytokeratin-18
timeFrame: From baseline to 3 months post-procedure
measure: Change in Liver Stiffness Measurement and Controlled Attenuation Parameter
timeFrame: From baseline to 3 months post-procedure
measure: Change in Enhanced Liver Fibrosis Test
timeFrame: From baseline to 3 months post-procedure
Other outcomes:
measure: Chang in Fasting Lipid Profile
timeFrame: From baseline to 3 months post-procedure
measure: Change in Concentration of Fasting Plasma Glucose (FPG)
timeFrame: From baseline to 3 months post-procedure
measure: Change in Concentration of Fasting serum insulin (FINS)
timeFrame: From baseline to 3 months post-procedure
measure: Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Index
timeFrame: From baseline to 3 months post-procedure
measure: Change in Percentage of Glycosylated Hemoglobin (Hba1c)
timeFrame: From baseline to 3 months post-procedure
measure: Change in Body Weight
timeFrame: From baseline to 3 months post-procedure
measure: Change in Waist Circumference
timeFrame: From baseline to 3 months post-procedure
measure: Change in Waist to Hip (WTH) Ratio
timeFrame: From baseline to 3 months post-procedure
measure: Change in Office Systolic Blood Pressure
timeFrame: From baseline to 3 months post-procedure
measure: Change in Office Diastolic Blood Pressure
timeFrame: From baseline to 3 months post-procedure
measure: Incidence of Adverse Events (AEs)
timeFrame: From baseline to 3 months post-procedure
measure: Incidence of Severe Adverse Events (SAEs)
timeFrame: From baseline to 3 months post-procedure
Locations:
city: Nanjing
country: China
facility: The Affiliated Jiangning Hospital of Nanjing Medical University
state: Jiangsu
city: Nanjing
country: China
facility: JiangSu Province Hospital / The First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
city: Suzhou
country: China
facility: Suzhou Municipal Hospital
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: shijing5499@jsph.org.cn Kong
role: PRINCIPAL_INVESTIGATOR
References:
citation: Xu C, Ma Z, Wang Y, Liu X, Tao L, Zheng D, Guo X, Yang X. Visceral adiposity index as a predictor of NAFLD: A prospective study with 4-year follow-up. Liver Int. 2018 Dec;38(12):2294-2300. doi: 10.1111/liv.13941. Epub 2018 Sep 6.
citation: Petta S, Amato MC, Di Marco V, Camma C, Pizzolanti G, Barcellona MR, Cabibi D, Galluzzo A, Sinagra D, Giordano C, Craxi A. Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2012 Jan;35(2):238-47. doi: 10.1111/j.1365-2036.2011.04929.x. Epub 2011 Nov 24.
citation: van der Poorten D, Milner KL, Hui J, Hodge A, Trenell MI, Kench JG, London R, Peduto T, Chisholm DJ, George J. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology. 2008 Aug;48(2):449-57. doi: 10.1002/hep.22350.