Focused Power Ultrasound Mediated Inferior Perirenal Adipose Tissue Modification Therapy for Non-Alcoholic Fatty Liver Disease (PARADISE-NAFLD)

Non-alcoholic Fatty Liver Disease Clinical Trial

Official title:

Focused Power Ultrasound Mediated Inferior Perirenal Adipose Tissue Modification Therapy for Non-Alcoholic Fatty Liver Disease: a Randomized Controlled Trial (PARADISE-NAFLD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06225713
• Other study ID #: PARADISE-NAFLD
• Status: Recruiting
• Phase: N/A
• Start date: February 2, 2024
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: Xiangqing Kong
• Phone: +8613951610265
• Email: kongxq[@]njmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 31, 2024
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease

Intervention

Device:
• focused power ultrasound mediated inferior perirenal adipose tissue modification
This novel focused power ultrasound is an externally delivered, completely noninvasive focused therapeutic ultrasound device. It is capable of focusing the resulting ultrasound beam to a small "cigar"-shaped volume and monitoring the temperature of the target area, which leads to the rapid elevation of the peri-renal adipose tissue temperature and the destruction of target tissue eventually.
• sham-control group
Participants will receive the sham control therapy (including peri-renal fat ultrasonic measurement and localization, focused ultrasound treatment parameters setting), however, without initiating the focused ultrasound equipment.

Locations

Country	Name	City	State
China	JiangSu Province Hospital / The First Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	The Affiliated Jiangning Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Suzhou Municipal Hospital	Suzhou	Jiangsu

Sponsors (3)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University	Suzhou Municipal Hospital, The Affiliated Jiangning Hospital of Nanjing Medical University

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Chang in Fasting Lipid Profile	These include triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol	From baseline to 3 months post-procedure
Other	Change in Concentration of Fasting Plasma Glucose (FPG)	Change in concentration of FPG at 3-month compared with baseline	From baseline to 3 months post-procedure
Other	Change in Concentration of Fasting serum insulin (FINS)	Change in concentration of FINS at 3-month compared with baseline	From baseline to 3 months post-procedure
Other	Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Index	From the results of FPG and FINS, insulin resistance will be estimated using the HOMA-IR algorithm: HOMA-IR = FPG (mmol/L) × FINS (µU/mL) / 22.5	From baseline to 3 months post-procedure
Other	Change in Percentage of Glycosylated Hemoglobin (Hba1c)	The structure of Hba1c is relatively stable. Its concentration can effectively reflect the average blood glucose level in the past 8-12 weeks. It should be expressed as a percentage of adult hemoglobin	From baseline to 3 months post-procedure
Other	Change in Body Weight	Body weight will be measured on a calibrated scale (to the nearest 0.1 kilogram). The measurement will be performed with the study subject in underwear and without shoes; or while wearing minimal indoor clothing	From baseline to 3 months post-procedure
Other	Change in Waist Circumference	Change in waist circumference at 3-month compared with baseline	From baseline to 3 months post-procedure
Other	Change in Waist to Hip (WTH) Ratio	The WTH ratio is calculated as the ratio of waist to hip circumference	From baseline to 3 months post-procedure
Other	Change in Office Systolic Blood Pressure	Change in office systolic blood pressure at 3-month compared with baseline	From baseline to 3 months post-procedure
Other	Change in Office Diastolic Blood Pressure	Change in office diastolic blood pressure at 3-month compared with baseline	From baseline to 3 months post-procedure
Other	Incidence of Adverse Events (AEs)	The Incidence AEs will be reported for each arm	From baseline to 3 months post-procedure
Other	Incidence of Severe Adverse Events (SAEs)	The Incidence SAEs will be reported for each arm	From baseline to 3 months post-procedure
Primary	Absolute Change in Liver Fat Content	Absolute change in liver fat content assessed by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) at 3-month compared with baseline	From baseline to 3 months post-procedure
Secondary	Relative Change in Liver Fat Content	Relative change in liver fat content assessed by MRI-PDFF at 3-month compared with baseline	From baseline to 3 months post-procedure
Secondary	Proportion of MRI-PDFF Responders	Proportion of MRI-PDFF responders in two groups at 3-month of treatment. MRI-PDFF responder is defined as a =30% relative reduction in MRI-PDFF between baseline and end of treatment	From baseline to 3 months post-procedure
Secondary	Change in Alanine Aminotransferase (ALT)	ALT is increased with liver damage. The blood levels of ALT are used to detect liver injury.	From baseline to 3 months post-procedure
Secondary	Change in Concentration of Cytokeratin-18	Change in concentration of cytokeratin-18 in two groups at 3-month of treatment	From baseline to 3 months post-procedure
Secondary	Change in Liver Stiffness Measurement and Controlled Attenuation Parameter	Change in liver stiffness measurement and controlled attenuation parameter measured by transient elastography at 3-month of treatment	From baseline to 3 months post-procedure
Secondary	Change in Enhanced Liver Fibrosis Test	The markers of fibrosis assessed in this test comprised hyaluronic acid, tissue inhibitor of metalloproteinase 1 and procollagen III N-terminal peptide; these are elevated during fibrogenesis as a result of activation of the hepatic stellate cell.	From baseline to 3 months post-procedure