Augmentation of Limb Perfusion With Contrast Ultrasound

Our laboratory has discovered that ultrasound (US) imaging together with clinically approved microbubble ultrasound contrast agents can augment limb tissue perfusion. These observations have been made in mice with and without peripheral artery disease (PAD), and also in humans where high power contrast enhanced ultrasound (CEU) was used to measure perfusion but was found also to augment perfusion by almost 2-fold. The latter human studies were performed with ultrasound protocols designed for perfusion imaging and not for flow augmentation. In this study, we will measure the degree to which limb perfusion is augmented with specific therapeutic CEU settings that are still within the FDA-approved limits with regards to US power and contrast dosing.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Device: Ultrasound

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jonathan R Lindner, MD; Phone Number: 5034943574; Email: lindnerj@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • OHSU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 y.o.
• For PAD subjects: known history of unilateral or bilateral PAD diagnosed by reduced ankle-brachial index or angiography and a Rutherford symptom class of 4-6.

Exclusion Criteria:

1. Major medical illness other than PAD affecting the limb (muscle disease, blood diseases that influence flow or rheology, severe heart failure [NYHA class IV or LVEF <30%]).
2. Pregnant or lactating females
3. Hypersensitivity to any ultrasound contrast agent
4. Known atrial septal defect or large right to left shunt.
5. Hemodynamic instability (hypotension with systolic BP <90 mm Hg, need for vasopressors)
6. Evidence for ongoing myocardial ischemia
7. For normal controls, any known structural non-arrhythmic cardiovascular disease (coronary artery disease, heart failure, moderate or greater valve disease).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Healthy subjects; Low-power contrast ultrasound perfusion imaging and measurement of ABI and TBI will be performed before and after a 15 min high-power ultrasound cavitation therapy with intermittent ultrasound and intravenous infusion of microbubbles.	Device: Ultrasound; Ultrasound exposure of Definity microbubbles infused over 10 min. Ultrasound administered at 1.3 MHz, mechanical index of 1.3, and pulsing interval of 10 s.; Other Names: Contrast ultrasound
EXPERIMENTAL: Peripheral Artery Disease; Low-power contrast ultrasound perfusion imaging and measurement of ABI and TBI will be performed before and after a 15 min high-power ultrasound cavitation therapy with intermittent ultrasound and intravenous infusion of microbubbles.	Device: Ultrasound; Ultrasound exposure of Definity microbubbles infused over 10 min. Ultrasound administered at 1.3 MHz, mechanical index of 1.3, and pulsing interval of 10 s.; Other Names: Contrast ultrasound

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood flow at 10 min	Change in blood flow in calf skeletal muscle	10 min post-therapeutic ultrasound cavitation.
Change in blood flow at 60 min	Change in blood flow in calf skeletal muscle	60 min post-therapeutic ultrasound cavitation

Collaborators and Investigators

• Sponsor: Oregon Health and Science University

Publications and helpful links

General Publications

• Mason OR, Davidson BP, Sheeran P, Muller M, Hodovan JM, Sutton J, Powers J, Lindner JR. Augmentation of Tissue Perfusion in Patients With Peripheral Artery Disease Using Microbubble Cavitation. JACC Cardiovasc Imaging. 2020 Mar;13(3):641-651. doi: 10.1016/j.jcmg.2019.06.012. Epub 2019 Aug 14.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 18, 2018
• Primary Completion (ANTICIPATED): December 1, 2019
• Study Completion (ANTICIPATED): December 1, 2019

Study Registration Dates

• First Submitted: June 16, 2017
• First Submitted That Met QC Criteria: June 19, 2017
• First Posted (ACTUAL): June 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 23, 2018
• Last Update Submitted That Met QC Criteria: August 21, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: IRB00017343

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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