Evaluation of Musculoskeletal Microcirculation With Ultrasound (EMMU)

This study aims to validate the use of Dynamic Contrast-Enhanced Ultrasound in measuring the blood supply to the muscles of the leg, and how this changes with exercise and vascular pathology.

Study Overview

• Status: Terminated
• Conditions: Standardised Claudication Treadmill Test
• Intervention / Treatment: Procedure: Contrast enhanced ultrasound; Behavioral: Treadmill test; Procedure: Contrast enhanced ultrasound

Detailed Description

We propose a model for the use of Dynamic Contrast-Enhanced Ultrasound (DCEU) to directly evaluate the microcirculation of the musculoskeletal system. We believe that this will be a valuable research tool into diseases of the microcirculation, and in the future may also offer a clinical benefit by quantifying and monitoring disease over time and after intervention. It may also allow targeting of therapies towards those patients most at risk of ulcers and peripheral neuropathy, and those that would get the maximum benefit from these therapies.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Group 1 - Healthy subjects Inclusion

• 18+ years old

Exclusion

• Personal history of diabetes or peripheral arterial disease, current pregnancy, previous surgery to the lower limb, heart attack within 4 weeks, or unstable angina

Group 2 - Peripheral arterial disease subjects Inclusion

• 18+ years old, radiological evidence of peripheral arterial disease (arterial doppler or angiogram), ankle-brachial pressure index (ABPI) 0.5-0.8

Exclusion

• Personal history of diabetes, current pregnancy, previous amputation, heart attack within 4 weeks, or unstable angina

Group 3 - Diabetic subjects Inclusion

• 18+ years old, with a clinical diagnoses of diabetes (1, 2)

Exclusion

- ABPI<0.9, previous amputation, current pregnancy or breastfeeding, heart attack within 4 weeks, or unstable angina.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy; Healthy volunteers, deemed to have normal metabolic and cardiovascular biology by trial criteria	Procedure: Contrast enhanced ultrasound; Infusion of microbubbles to enhance blood vessels in the leg for ultrasound; Behavioral: Treadmill test; Exposes you to exercise in a controlled environment. We will see if we can detect this change with our new ultrasound protocol; Procedure: Contrast enhanced ultrasound
Active Comparator: PAD; Symptomatic peripheral arterial disease	Procedure: Contrast enhanced ultrasound; Infusion of microbubbles to enhance blood vessels in the leg for ultrasound; Behavioral: Treadmill test; Exposes you to exercise in a controlled environment. We will see if we can detect this change with our new ultrasound protocol; Procedure: Contrast enhanced ultrasound
Active Comparator: DM; Symptomatic diabetic peripheral neuropathy	Procedure: Contrast enhanced ultrasound; Infusion of microbubbles to enhance blood vessels in the leg for ultrasound; Behavioral: Treadmill test; Exposes you to exercise in a controlled environment. We will see if we can detect this change with our new ultrasound protocol; Procedure: Contrast enhanced ultrasound

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Threshold of High to Low Frequency Ratio (Threshold HLFR)	Please see published article for in depth method. This ratio is used to classify a given signal as either microbubble or noise. For a pixel containing a micro vessel, as microbubbles occasionally pass this otherwise dark pixel, its temporal signal is expected to have a higher proportion of lower frequency components than white noise. Consequently, the HLFR of the pixel is expected to be smaller than that of noise. A histogram of normalised HLFR shows two expected peaks (one noise, one bubbles). A threshold (Threshold HLFR) is determined to then separate the two peaks. this is done using a double Gaussian model, and where they intercept is deemed the Threshold HLFR.	Baseline, 20 minutes

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Prof AH Davies, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: January 9, 2014
• First Submitted That Met QC Criteria: March 11, 2014
• First Posted (Estimate): March 13, 2014

Study Record Updates

• Last Update Posted (Actual): November 25, 2020
• Last Update Submitted That Met QC Criteria: November 2, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: treadmill test
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Intermittent Claudication
• Other Study ID Numbers: 13/LO/0943; 13HH0684 (Other Identifier: Imperial College London)

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