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

NCT ID: NCT06225713

Last Updated: 2024-06-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-02
• Study Completion Date: 2024-12-31

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.

Conditions

Non-alcoholic Fatty Liver Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

intervention group

In intervention group, participants will receive the whole peri-renal fat modification therapy (including peri-renal fat ultrasonic measurement and localization, focused ultrasound treatment parameters setting and initiating)

Group Type: EXPERIMENTAL

focused power ultrasound mediated inferior perirenal adipose tissue modification

Intervention Type: DEVICE

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

In 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.

Group Type: SHAM_COMPARATOR

sham-control group

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: DEVICE

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.

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Affiliated Jiangning Hospital of Nanjing Medical University

OTHER

Sponsor Role: collaborator

Suzhou Municipal Hospital

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Xiangqing Kong

Head of Cardiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

shijing5499@jsph.org.cn Kong

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital with Nanjing Medical University

Locations

The Affiliated Jiangning Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Site Status: RECRUITING

JiangSu Province Hospital / The First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Site Status: RECRUITING

Suzhou Municipal Hospital

Suzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiangqing Kong

Role: CONTACT

kongxq@njmu.edu.cn

+8613951610265

Jing Shi

Role: CONTACT

shijing5499@jsph.org.cn

+8615051872305

Facility Contacts

Qibin He

Role: primary

Xiangqing Kong

Role: primary

kongxq@njmu.edu.cn

+8613951610265

Yanhui Sheng

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 30099825 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22117531 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18627003 (View on PubMed)

Other Identifiers

PARADISE-NAFLD

Identifier Type: -

Identifier Source: org_study_id