Ultrasound Wave Therapy for Post-stenotic Microvascular Remodeling

Researchers are evaluating a noninvasive treatment with ultrasound waves for Atherosclerotic Renal Artery Stenosis (ARAS).

Study Overview

• Status: Withdrawn
• Conditions: Renal Artery Stenosis
• Intervention / Treatment: Device: Low-energy extracorporeal ultrasound shockwave therapy (SWT)

Detailed Description

Investigators will study 30 patients with ARAS randomized to SWT or sham (n=15 each) twice a week over 3 weeks. We will measure before and again 3 months after a 3-wk regimen renal cortical and medullary perfusion and function (multi-detector computed tomography [MDCT]), oxygenation, and fibrosis (magnetic resonance imaging [MRI]), urinary and plasma levels of renal injury markers, systemic endothelial function, and heart rate variability, an index of sympathetic activation.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Patients are between ages 40 and 80 years old.
• Patients with hypertension (Systolic BP> 155 mm Hg) and/or requirement for two or more antihypertensive medications for more than 4 weeks, no restrictions on antihypertensive agents, although loop diuretics may be changed to diluting site agents (e.g. hydrochlorothiazide, indapamide, metolazone) for two weeks prior to study.
• Patients have serum creatinine ≤2.2 mg/dL.
• Patients have no contraindications to angiography: severe contrast allergy.
• Patients have no contraindications to no-contrast MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia.
• Patients have the ability to comply with protocol
• Patients are competent and able to provide written informed consent

Exclusion Criteria

• Patient have serum creatinine >2.2 mg/dL
• ARAS in a solitary kidney
• Patients have clinically significant medical conditions within the six months before SWT treatment: e.g. myocardial infarction, congestive heart failure, stroke, that would, in the opinion of the investigators, compromise the safety of the patient.
• Uncontrolled hypertension (Systolic BP >180 mmHg despite therapy).
• Pacemaker, implantable defibrillator or other contraindication to MRI
• Inability to comply with breath-hold for 20 seconds
• Any active malignancy and undergoing therapy
• Patients are pregnant.
• Kidney or ureteric stone that may affect the effect of SWT.
• Another known acute or chronic kidney disease
• Local inflammation or infection over treatment areas.
• Bleeding disorders.
• Federal medical center inmates.
• Latex allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 15 patients with ARAS randomized to SWT; We will study 15 patients with ARAS randomized to SWT twice a week over 3 weeks. We will measure before and again 3 months after a 3-wk regimen renal cortical and medullary perfusion and function (multi-detector computed tomography [MDCT]), oxygenation, and fibrosis (magnetic resonance imaging [MRI]), urinary and plasma levels of renal injury markers, systemic endothelial function, and heart rate variability, an index of sympathetic activation.	Device: Low-energy extracorporeal ultrasound shockwave therapy (SWT); SWT delivers 10% energy of the traditional SWT used for clinically indicated lithotripsy, evokes neovascularization, and improves regional blood flow and function in various ischemic tissues.
Sham Comparator: 15 patients with ARAS sham; we will study 15 patients with ARAS randomized to or sham twice a week over 3 weeks. We will measure before and again 3 months after a 3-wk regimen renal cortical and medullary perfusion and function (multi-detector computed tomography [MDCT]), oxygenation, and fibrosis (magnetic resonance imaging [MRI]), urinary and plasma levels of renal injury markers, systemic endothelial function, and heart rate variability, an index of sympathetic activation.	Device: Low-energy extracorporeal ultrasound shockwave therapy (SWT); SWT delivers 10% energy of the traditional SWT used for clinically indicated lithotripsy, evokes neovascularization, and improves regional blood flow and function in various ischemic tissues.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in kidney perfusion assessed by computed tomography	Single-kidney perfusion and GFR assessed by multi-detector computed tomography (MDCT)	Baseline, 3 months
Change in renal function assessed by GFR	Renal function by eGFR calculated by both the modified modification of Diet in Renal Disease (MDRD) formula, and measured GFR (mGFR) by iothalamate clearance	Baseline, 3 months
Change in blood oxygen in kidney assessed by MRI	Cortical and medullary oxygenation assessed by Blood oxygen-level-dependent (BOLD)-MRI	Baseline, 3 months
Change in renal fibrosis assessed by MRI	Renal fibrosis as determined by Magnetization transfer imaging (MTI)-MRI in vivo.	Baseline, 3 months
Change in urinary levels of biomarkers and extracellular vehicles	Urinary biomarkers albumin, renal injury markers: Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecular (KIM)-1, and lactate dehydrogenase (LDH)], as well as urinary levels of extracellular vehicles (EVs) (measured by flow cytometry) originating from renal microvessels.	Baseline, 3 months
Change in labs collected from right and left renal veins and/or Inferior Vena Cava	Serum creatinine, plasma renin activity (PRA), aldosterone, cytokines and circulating endothelial progenitor cell (EPC) in blood collected from the left and right renal veins and the Inferior Vena Cava (IVC).	Baseline, 3 months
Change in mean arterial pressure assessed by oscillometry	systolic and diastolic BP will be measured by oscillometry to calculate MAP, and assessment of sympathetic nervous system activation by heart rate variability (HRV).	Baseline, 3 months
Change in peripheral microvascular endothelial function assessed in the fingertip	Peripheral microvascular endothelial function by peripheral arterial tonometry (EndoPAT).	Baseline, 3 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Rajiv Gulati, MD, PhD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): December 1, 2027
• Study Completion (Anticipated): December 1, 2027

Study Registration Dates

• First Submitted: April 9, 2019
• First Submitted That Met QC Criteria: April 10, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Kidney Diseases; Urologic Diseases; Renal Artery Obstruction
• Other Study ID Numbers: 18-007617; R01HL123160 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We do not intend to make individual participant data (IPD) available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No