Administrative information
Title {1} | Effect of focused power ultrasound-mediated perirenal fat modification on primary hypertension: protocol of a multicenter, randomized, double-blinded, sham-controlled study |
---|---|
Trial registration {2a and 2b}. | ClinicalTrials.gov Identifier: NCT05049096. Registered on September 7, 2021.https://clinicaltrials.gov/ct2/show/NCT05049096?term=05049096&draw=2&rank=1 |
Protocol version {3} | Version 1.3.1, data 23 August 2021 |
Funding {4} | This work was funded by the National Natural Science Foundation of China (No.82150002, No.81627802) and the Science Foundation of Gusu School (No. GSKY20220102). |
Author details {5a} | 1. Menghuan Li, M.D., The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 2. Jing Shi, Ph.D., The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. 3. Yanhui Sheng, Ph.D., The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China. 4. Yuqing Zhang, M.D., The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. 5. Tinting Wu, M.D., The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. 6. Jiaming Yang, M.D., The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. 7. Kerui Zhang, M.D., Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China. 8. Wei Sun, M.D., Ph.D., The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. 9. Xiangqing Kong, M.D., Ph.D., The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China. |
Name and contact information for the trial sponsor {5b} | Prof. Xiangqing Kong (principal investigator), The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; Email: kongxq@njmu.edu.cn. Phone: 02568303130. Contact for public and scientific queries: Wei Sun, Email: shunwee@126.com. |
Role of sponsor {5c} | Prof. Xiangqing Kong serves as the principal investigator of this trial and applied for scientific financial support. The funders played no role in the study design, implementation, data analysis, and results publication. |
Introduction
Background and rationale
Objectives
Trial design
Methods: participants, intervention, and outcomes
Study setting
Eligibility criteria
-
• Individuals aged 18–65 years old
-
• Individuals have uncontrolled BP when receiving a medication regimen of one, two, or three antihypertensive medication classes for at least 4 weeks; and uncontrolled BP is defined as office systolic blood pressure (SBP) ≥ 140 mmHg and < 180 mmHg, and 24-h ambulatory BP monitoring (ABPM) average SBP ≥ 135 mmHg, regardless of diastolic BP
-
• Individuals have at least 20 mm in the anteroposterior, transverse, and axial diameters of inferior perirenal fat measured by ultrasound
-
• Individuals are willing to sign the informed consent of the study
-
• Individuals are diagnosed with secondary hypertension (e.g., renal parenchymal hypertension, renal artery stenosis, primary aldosteronism, pheochromocytoma, Cushing’s syndrome, aortic coarctation, severe obstructive sleep apnea-hypopnea syndrome)
-
• Individuals have a history of kidney and or kidney surrounding tissue surgery
-
• Individuals have impairment of liver or kidney function (ALT, AST, or creatinine is greater than 3 times the upper limit of normal reference)
-
• Individuals have a myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack within 6 months before enrollment
-
• Individuals have type 1 diabetes or poorly-controlled type 2 diabetes
-
• Individuals have uncontrolled thyroid dysfunction
-
• Individuals have urinary calculi and/or hematuria
-
• Individuals have atrial fibrillation
-
• Individuals have severe structural heart disease (e.g., heart valve disease, cardiomyopathy, congenital heart disease)
-
• Individuals have second-degree and above atrioventricular block
-
• Individuals have abnormal coagulation function
-
• Individuals have infected waist skin
-
• Individuals have a malignant tumor
-
• Individuals are pregnant, nursing, or planning to be pregnant
-
• Individuals are unwilling to sign informed consent
-
• Individuals fail to complete the screening period
Intervention
PFM procedure
Sham procedure
Criteria for discontinuing
-
• They may choose to withdraw for any reason
-
• They have severe side effects that require unmarking to get cured
-
• Their blood pressure is within “escape criteria,” defined as office SBP ≥ 180mmHg or < 90 mmHg
-
• They have a significant deviation from the study algorithm, e.g., changing the established antihypertensive drugs scheme
-
• Any other rational reasons to withdraw from the study
Strategies to improve adherence
Relevant concomitant care and interventions
Outcomes
-
• Changes in office systolic blood pressure at 1-month compared with baseline
-
• Changes in office blood pressure at 3 months compared with baseline
-
• Changes in mean systolic blood pressure measured by 24-h ambulatory blood pressure monitoring at 1 month compared with baseline
-
• Changes in mean systolic blood pressure measured by 24-h ambulatory blood pressure monitoring at 3 months compared with baseline
-
• Changes in the heart rate at 1 month compared with baseline
-
• Changes in the mean heart rate measured by 24-h ambulatory blood pressure monitoring at 1 month compared with baseline
-
• Any severe adverse events (SAE) related to the intervention. The SAE was defined as acute renal failure, acute intestinal perforation, and thromboembolic events, etc.
Participant timeline
Study period | ||||||
---|---|---|---|---|---|---|
Enrolment | Allocation | Post-allocation | Close-out | |||
Timepoint | − 14 days | Day 0 | Day 1 | Day 14 | Day 30 | Day 90 |
Enrolment: | ||||||
Eligibility screen | X | |||||
Informed consent | X | |||||
Interventions: | ||||||
PFM | X | |||||
Sham-control | X | |||||
Assessments: | ||||||
Office BP measurement | X | X | X | X | X | |
24-h ambulatory BP measurement | X | X | X | X | ||
History of diseases | X | |||||
Physical examinations | X | X | X | |||
Drugs use record | X | X | X | X | ||
Antihypertensive drugs concentration tests | X | X | X | |||
Blood routine | X | X | X | X | ||
Biochemical test | X | X | X | X | ||
C-reactive protein | X | X | ||||
Biomarkers of acute renal injury | X | X | ||||
ECG | X | X | X | X | ||
Renal and renal artery ultrasound | X | X | X | X | ||
Carotid ultrasound | X | X | X | X | ||
Cardiac ultrasound | X | |||||
MR imaging of perirenal fat | X | X | X | |||
Functional MR imaging of hypothalamus | X | X | X |
Sample size
Recruitment
Assignment of interventions: allocation
Sequence generation
Concealment mechanism
Implementation
Blinding
Methods: data collection, management, and analysis
Data collection
Baseline data collection
-
• Written informed consent
-
• Clinical questionnaire
-
• Office BP and 24-h ambulatory BP
-
• Anthropometric information including height, weight, waist circumference, and hip circumference
-
• Electrocardiography and cardiac ultrasound
-
• Arteries stiffness assessments (PWV)
-
• Imaging examinations including ultrasonic examinations of renal and perirenal fat, carotid ultrasound, and magnetic resonance imaging for perirenal fat and hypothalamic function
-
• Blood tests including routine blood tests, blood biochemical tests, and C-reactive protein
-
• Urine tests including routine urine tests, urine biomarkers of acute renal injury (Ngal, TIMP2, IGFBP7)
-
• Hypertensive drug concentration detection (serum and urine)
Data collection at 1 day after intervention
-
• Office BP and 24-h ambulatory BP
-
• Electrocardiography
-
• Arteries stiffness assessments (PWV)
-
• Imaging examinations including ultrasonic examinations of renal and perirenal fat and carotid ultrasound
-
• Blood tests including routine blood tests, blood biochemical tests, and C-reactive protein
-
• Urine tests including routine urine tests and urine biomarkers of acute renal injury (Ngal, TIMP2, IGFBP7)
Data collection at 14 days after intervention
-
• Office BP
Data collection at 30 days after intervention
-
• Office BP and 24-h ambulatory BP
-
• Anthropometric information including height, weight, waist circumference, and hip circumference
-
• Electrocardiography
-
• Arteries stiffness assessments (PWV)
-
• Imaging examinations including ultrasonic examinations of renal and perirenal fat, carotid ultrasound, and magnetic resonance imaging for perirenal fat and hypothalamic function
-
• Blood tests including routine blood tests, and biochemical blood tests
-
• Urine tests including routine urine tests
-
• Hypertensive drug concentration detection (serum and urine)
Data collection at the final visit
-
• Office BP and 24-hour ambulatory BP
-
• Anthropometric information including height, weight, waist circumference, and hip circumference
-
• Electrocardiography
-
• Arteries stiffness assessments (PWV)
-
• Imaging examinations including ultrasonic examinations of renal and perirenal fat, carotid ultrasound, and magnetic resonance imaging for perirenal fat and hypothalamic function
-
• Blood tests including routine blood tests, and biochemical blood tests
-
• Urine tests including routine urine tests
-
• Hypertensive drug concentration detection (serum and urine)