EMMU: Evaluation of Musculoskeletal Microcirculation With Ultrasound

• Sponsor: Imperial College London (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02086331
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arms: 3
• Actual Duration (Months): 24
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Standardised Claudication Treadmill Test	Procedure: Contrast enhanced ultrasound; Behavioral: Treadmill test; Procedure: Contrast enhanced ultrasound	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Evaluation of Musculoskeletal Microcirculation With Ultrasound
• Actual Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Threshold of High to Low Frequency Ratio (Threshold HLFR) [Baseline, 20 minutes]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Charing Cross Hospital	London		United Kingdom	W6 8RF

Sponsors and Collaborators

• Imperial College London

Investigators

• Principal Investigator: Prof AH Davies, Imperial College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT02086331
• Other Study ID Numbers: 13/LO/0943; 13HH0684
• First Posted: Mar 13, 2014
• Last Update Posted: Nov 25, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College London: treadmill test
• Additional relevant MeSH terms: Intermittent Claudication

Study Results

Participant Flow

Pre-assignment Detail	This study was terminated early after the proof of concept stage. We showed that our methodology worked in healthy subjects, then ran out of time thus no participants were enrolled in either the "Symptomatic peripheral arterial disease" or "Symptomatic diabetic peripheral neuropathy" arms.

Arm/Group Title	Healthy
Arm/Group Description	Healthy participants
Period Title: Overall Study
STARTED	5
COMPLETED	5
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Healthy Subjects
Arm/Group Description
Overall Participants	5
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	23
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%

Outcome Measures

1. Primary Outcome

Title	Threshold of High to Low Frequency Ratio (Threshold HLFR)
Description	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.
Time Frame	Baseline, 20 minutes

Outcome Measure Data

Analysis Population Description

5 recruits imaged and analysed. One recruit of five was excluded due to acquisition error

Arm/Group Title	Subject 1	Subject 2	Subject 3	Subject 4
Arm/Group Description
Measure Participants	1	1	1	1
At rest	0.12	0.093	0.16	0.4
After treadmill protocol, 20mins	0.167	0.14	0.15	0.35

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subject 1, Subject 2, Subject 3, Subject 4
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Intraclass correlation of repeated measures - 0.96, p=0.08

2. Post-Hoc Outcome

Title	Average Percentage Change in Microbubble Track Density Measure (MTD)
Description	The number of pixels identified as having bubble signals was normalised by dividing by area of region of interest (ROI). MTD = pixels with microbubbles / area of ROI Used as a surrogate for active vascular density. The percentage change between rest and exercise (20 minute treadmill protocol) was calculated on each day
Time Frame	Test repeated on consecutive day to measure repeatability

Outcome Measure Data

Analysis Population Description

One subject out of five excluded for acquisition error

Arm/Group Title	Day 1	Day 2
Arm/Group Description
Measure Participants	4	4
Mean (Standard Deviation) [% change from baseline]	138.2 (79.8)	119.4 (62.7)

Adverse Events

Arm/Group Title	Subject 1		Subject 2		Subject 3		Subject 4		Subject 5
Arm/Group Description
All Cause Mortality
	Subject 1		Subject 2		Subject 3		Subject 4		Subject 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/1 (0%)		0/1 (0%)
Serious Adverse Events
	Subject 1		Subject 2		Subject 3		Subject 4		Subject 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Subject 1		Subject 2		Subject 3		Subject 4		Subject 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/1 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.