This seamless two-stage phase II/III clinical trial aims to evaluate the efficacy and safety of a novel focused power ultrasound mediated inferior perirenal adipose tissue modification therapy for essential hypertension. Stage 1 is a phase II, multicenter, open-label, randomized trial to determine the optimal treatment strategy. Stage 2 is a phase III, multicenter, randomized, double-blind trial investigating the efficacy and safety of optimal treatment strategy compared to sham control.

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 the investigators' previous experiments, this novel focused power ultrasound can rapidly and efficiently promote the perirenal adipose tissue fibrosis and control the blood pressure 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 perirenal adipose tissue in human volunteers, showing that this kind of method was feasible and safe.

This seamless two-stage phase II/III clinical trial aims to evaluate the efficacy and safety of a novel focused power ultrasound mediated inferior perirenal adipose tissue modification therapy for essential hypertension. In Stage 1, 30 participants will be 1:1:1 randomly allocated to 3 intervention groups (single treatment group, consecutive treatment group A, and consecutive treatment group B). The optimal treatment strategy will be selected based on the decrease of blood pressure and safety evaluation and proceed to Stage 2. In Stage 2, participants will be randomly assigned to intervention group (optimal treatment strategy selected formerly in Stage 1) and sham control group.

Inclusion Criteria:

1. Individual with office systolic blood pressure (SBP) ≥ 140 mmHg and <160 mmHg, and office diastolic blood pressure (DBP)<100mmHg after standardized antihypertensive drug treatment for 1 month;
2. Individual with 24-hour Ambulatory Blood Pressure Monitoring (ABPM) average systolic blood pressure (ASBP) ≥130 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 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. Individuals with ≥ 3 cardiovascular risk factors (male>55 years old, female>65 years old; smoking or passive smoking; 2-hour postprandial blood glucose 7.8-11mmol/L and/or impaired fasting glucose (6.1-6.9mmol/L); LDL-C ≥ 3.4mmol/L (130mg/dl), HDL-C<1.0mmol/L (40mg/dl) or TC ≥ 5.2mmol/L (200mg/dl); Family history of early onset of cardiovascular disease, age of onset of first degree relatives<50 years old; Abdominal obesity, waist circumference: male>90cm, female>85cm or BMI>28kg/m2) or hypertensive target organ damage;
3. riser hypertension (defined as night blood pressure higher than daytime blood pressure by ABPM)
4. Regular night shift workers
5. Individuals taking other medications that may affect blood pressure (such as glucocorticoids);
6. Individual with history of kidney or kidney surrounding tissue surgery;
7. Individuals with impairment of liver or kidney function (ALT, AST or creatinine greater than 2 times of the upper limit of normal reference);
8. Individual with myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack within 6 months of enrollment;
9. Individual with type 1 diabetes or uncontrolled type 2 diabetes；
10. Individual with uncontrolled thyroid dysfunction;
11. Individual with urinary calculi or hematuria；
12. Individual with atrial fibrillation;
13. Individual with severe structural heart disease (e.g. valvular heart disease, cardiomyopathy, congenital heart disease);
14. Individual with second degree and above atrioventricular block and/or sick sinus syndrome;
15. Individual with abnormal coagulation function;
16. Individual with infected waist skin;
17. Individual with claustrophobia；
18. Individual with malignant tumor;
19. History of allergy to amlodipine, olmesartan, and hydrochlorothiazide
20. Individual is pregnant, nursing or planning to be pregnant;
21. Individual is unwilling to sign informed consent;
22. Individual fails to complete the screening period.