Ultrasound Wave Therapy for Post-stenotic Microvascular Remodeling

NCT03914157 | Withdrawn FDA Device

• 2 other identifiers: 18-007617R01HL123160
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Renal Artery Stenosis

Outcome Measures

Primary Outcomes (8)

• 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

Study Arms (2)

15 patients with ARAS randomized to SWT

ACTIVE COMPARATOR

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)

15 patients with ARAS sham

SHAM COMPARATOR

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)

Interventions

Low-energy extracorporeal ultrasound shockwave therapy (SWT) DEVICE

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.

15 patients with ARAS randomized to SWT; 15 patients with ARAS sham

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Renal Artery Obstruction

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Rajiv Gulati, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: We 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 Record Dates

• First Submitted: April 9, 2019
• First Posted: April 16, 2019
• Study Start: March 1, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 9, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share