Focused Power Ultrasound Mediated Inferior Perirenal Adipose Tissue Modification Therapy for Essential Hypertension (PARADISE-HTN)

Focused Power Ultrasound Mediated Inferior Perirenal Adipose Tissue Modification Therapy for Essential Hypertension: a Multicenter, Randomized, Double-blinded Controlled Trial. PARADISE Study

This randomized, double 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 essential hypertension.

Study Overview

• Status: Terminated
• Conditions: Cardiovascular Diseases; Hypertension; Blood Pressure
• Intervention / Treatment: Device: focused power ultrasound mediate inferior perirenal adipose tussue modification; Device: sham-control group

Detailed Description

The increase of visceral fat is closely related to the occurrence of hypertension, and it is one of the main independent risk factors of hypertension. Visceral fat has been recognized as an important endocrine organ, and a variety of factors secreted by visceral fat lead to an increased risk of cardiovascular disease. Peri-renal fat is a special type of visceral fat which is different from other type of visceral fat in histology, physiology, and functions. The positon of peri-renal fat is more stable than other visceral fat, which might be influenced by breath or body position changes.Studies have found that perirenal fat is an early predictor of ASCVD, and its accumulation is closely related to the occurrence and development of ASCVD.Therefore, the reduction or modification of visceral fat,especially peri-renal fat , has a sufficient scientific basis for the treatment of hypertension.

In our previous experiments, this novel focused power ultrasound can rapidly and efficiently promote the perirenal adipse tissue fibrosis and control the blood pressure in the model of swine. Moreover, we performed a single arm, small sample study to investigate the feasibility of the novel focused power ultrasound to modify the inferior perirenal adipose tissue in human volunteers, showing that this kind of method was feasible and safe.

In this study, we aim to further evaluate the efficacy and safety of a novel focused power ultrasound mediated inferior perirenal adipose tissue modification therapy for essential hypertension.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Jiangsu Province Hospital/The Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China, 210000
      • The Affiliated Jiangning Hospital of Nanjing Medical University
    • Suzhou, Jiangsu, China, 215000
      • Suzhou Municipal Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Individual has office systolic blood pressure (SBP) ≥ 140 mmHg and <180 mmHg when receiving a medication regimen of one, two, or three antihypertensive medication classes；
2. Individual has 24-hour Ambulatory Blood Pressure Monitoring (ABPM) average SBP≥135 mmHg；
3. The anteroposterior, transverse and axial diameters of inferior perirenal fat pad measured by ultrasound should be at least 20mm；
4. Individual is willing to sign the informed consent of the study.

Exclusion Criteria:

1. Individual is diagnosed as secondary hypertension (e.g. renal parenchymal hypertension, renal artery stenosis, primary aldosteronism, pheochromocytoma, Cushing's syndrome, aortic coarctation, obstructive sleep apnea hypopnea syndrome)；
2. Individual has history of kidney and or kidney surrounding tissue surgery;
3. Individuals has impairment of liver or kidney function (ALT, AST or creatinine is greater than 2 times of the upper limit of normal reference);
4. Individual has myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack within 6 months of enrollment;
5. Individual has type 1 diabetes or poorly-controlled type 2 diabetes；
6. Individual has uncontrolled thyroid dysfunction;
7. Individual has urinary calculi and/or hematuria；
8. Individual has atrial fibrillation;
9. Individual has severe structural heart disease (e.g. heart valve disease, cardiomyopathy, congenital heart disease);
10. Individual has second degree and above atrioventricular block；
11. Individual has abnormal coagulation function;
12. Individual has infected waist skin;
13. Individual has malignant tumor;
14. Individual is pregnant, nursing or planning to be pregnant;
15. Individual is unwilling to sign informed consent;
16. Individual fails to complete the screening period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Device: focused power ultrasound mediate inferior perirenal adipose tussue 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 Comparator: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Office Systolic Blood Pressure	Changes of office systolic blood pressure at 1-month compared with baseline	From baseline to 1 month post-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Office Systolic Blood Pressure	Changes of office blood pressure at 3-month compared with baseline	From baseline to 3 months post-procedure
Ambulatory Blood Pressure	Changes of mean systolic blood pressure measured by 24-hour ambulatory blood pressure monitoring at 1-month compared with baseline	From baseline to 1 month post-procedure
Ambulatory Blood Pressure	Changes of mean systolic blood pressure measured by 24-hour ambulatory blood pressure monitoring at 3-month compared with baseline	From baseline to 3 months post-procedure
Heart Rate	Changes of the heart rate at 1-month compared with baseline	From baseline to 1 month post-procedure
Mean Heart Rate	Changes of the mean heart rate measured by 24-hour ambulatory blood pressure monitoring at 1-month compared with baseline	From baseline to 1 month post-procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation	Any severe adverse events (SAE) related to intervention. The SAE were defined as acute renal failure, acute intestinal perforation, and thromboembolic events, et al.	From baseline to 1 month post-procedure

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Principal Investigator: Xiangqing Kong, MD, Jiangsu province Hospital/The First Affiliated Hospital of Nanjing Medical University

Publications and helpful links

General Publications

• Hayashi T, Boyko EJ, Leonetti DL, McNeely MJ, Newell-Morris L, Kahn SE, Fujimoto WY. Visceral adiposity is an independent predictor of incident hypertension in Japanese Americans. Ann Intern Med. 2004 Jun 15;140(12):992-1000. doi: 10.7326/0003-4819-140-12-200406150-00008.
• Chandra A, Neeland IJ, Berry JD, Ayers CR, Rohatgi A, Das SR, Khera A, McGuire DK, de Lemos JA, Turer AT. The relationship of body mass and fat distribution with incident hypertension: observations from the Dallas Heart Study. J Am Coll Cardiol. 2014 Sep 9;64(10):997-1002. doi: 10.1016/j.jacc.2014.05.057.
• Djawari D, Haneke E. [Therapy of recurrent oral aphthae with thymopoetin pentapeptide]. Hautarzt. 1983 Sep;34(9):463-4. German.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Actual): November 20, 2023
• Study Completion (Actual): November 20, 2023

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: September 15, 2021
• First Posted (Actual): September 17, 2021

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Hypertension; Focused ultrasound; Novel method
• Additional Relevant MeSH Terms: Vascular Diseases; Hypertension; Cardiovascular Diseases; Essential Hypertension
• Other Study ID Numbers: PARADISE-HTN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No