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Ultrasound Wave Therapy for Post-stenotic Microvascular Remodeling

Primary Purpose

Renal Artery Stenosis

Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Low-energy extracorporeal ultrasound shockwave therapy (SWT)
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Renal Artery Stenosis

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Sham Comparator

    Arm Label

    15 patients with ARAS randomized to SWT

    15 patients with ARAS sham

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    Change in kidney perfusion assessed by computed tomography
    Single-kidney perfusion and GFR assessed by multi-detector computed tomography (MDCT)
    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
    Change in blood oxygen in kidney assessed by MRI
    Cortical and medullary oxygenation assessed by Blood oxygen-level-dependent (BOLD)-MRI
    Change in renal fibrosis assessed by MRI
    Renal fibrosis as determined by Magnetization transfer imaging (MTI)-MRI in vivo.
    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.
    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).
    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).
    Change in peripheral microvascular endothelial function assessed in the fingertip
    Peripheral microvascular endothelial function by peripheral arterial tonometry (EndoPAT).

    Secondary Outcome Measures

    Full Information

    First Posted
    April 9, 2019
    Last Updated
    May 5, 2023
    Sponsor
    Mayo Clinic
    Collaborators
    National Heart, Lung, and Blood Institute (NHLBI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03914157
    Brief Title
    Ultrasound Wave Therapy for Post-stenotic Microvascular Remodeling
    Official Title
    Ultrasound Wave Therapy for Post-stenotic Microvascular Remodeling
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2023
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Unable to support study
    Study Start Date
    March 2023 (Anticipated)
    Primary Completion Date
    December 2027 (Anticipated)
    Study Completion Date
    December 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Mayo Clinic
    Collaborators
    National Heart, Lung, and Blood Institute (NHLBI)

    4. Oversight

    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
    Data Monitoring Committee
    No

    5. Study Description

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

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Renal Artery Stenosis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    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.
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    15 patients with ARAS randomized to SWT
    Arm Type
    Active Comparator
    Arm Description
    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.
    Arm Title
    15 patients with ARAS sham
    Arm Type
    Sham Comparator
    Arm Description
    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.
    Intervention Type
    Device
    Intervention Name(s)
    Low-energy extracorporeal ultrasound shockwave therapy (SWT)
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Change in kidney perfusion assessed by computed tomography
    Description
    Single-kidney perfusion and GFR assessed by multi-detector computed tomography (MDCT)
    Time Frame
    Baseline, 3 months
    Title
    Change in renal function assessed by GFR
    Description
    Renal function by eGFR calculated by both the modified modification of Diet in Renal Disease (MDRD) formula, and measured GFR (mGFR) by iothalamate clearance
    Time Frame
    Baseline, 3 months
    Title
    Change in blood oxygen in kidney assessed by MRI
    Description
    Cortical and medullary oxygenation assessed by Blood oxygen-level-dependent (BOLD)-MRI
    Time Frame
    Baseline, 3 months
    Title
    Change in renal fibrosis assessed by MRI
    Description
    Renal fibrosis as determined by Magnetization transfer imaging (MTI)-MRI in vivo.
    Time Frame
    Baseline, 3 months
    Title
    Change in urinary levels of biomarkers and extracellular vehicles
    Description
    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.
    Time Frame
    Baseline, 3 months
    Title
    Change in labs collected from right and left renal veins and/or Inferior Vena Cava
    Description
    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).
    Time Frame
    Baseline, 3 months
    Title
    Change in mean arterial pressure assessed by oscillometry
    Description
    systolic and diastolic BP will be measured by oscillometry to calculate MAP, and assessment of sympathetic nervous system activation by heart rate variability (HRV).
    Time Frame
    Baseline, 3 months
    Title
    Change in peripheral microvascular endothelial function assessed in the fingertip
    Description
    Peripheral microvascular endothelial function by peripheral arterial tonometry (EndoPAT).
    Time Frame
    Baseline, 3 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    40 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Rajiv Gulati, MD, PhD
    Organizational Affiliation
    Mayo Clinic
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    We do not intend to make individual participant data (IPD) available to other researchers.
    Links:
    URL
    https://www.mayo.edu/research/clinical-trials
    Description
    Mayo Clinic Clinical Trials

    Learn more about this trial

    Ultrasound Wave Therapy for Post-stenotic Microvascular Remodeling

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