Condition category
Circulatory System
Date applied
17/07/2019
Date assigned
15/08/2019
Last edited
16/08/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Maintaining adequate perfusion of blood and nutrients to all regions of the body is a key aim for all clinicians, but perfusion is difficult to measure directly. Many indirect whole-body measures are used such as blood pressure. In clinical settings, examination of the skin provides useful information about whole-body perfusion. Clinical examination is known to add more to the overall assessment of a patient's clinical state than just the vital sign measurements. Skin blood flow in healthy individuals varies from almost nothing to up to 60% of the heart's output of blood depending on the circumstances. In situations of circulatory collapse, the body's response is to cut down the amount of blood supplying the skin and redirect them to the more vital areas. This change can be detected on examination as pale (or mottled/marbled appearance of skin) and cool skin, but may also be detected by video cameras. The researchers have previously designed and ran a healthy volunteer study to develop non-invasive and non-contact measurement of blood flow velocity to reflect the underlying circulation. The changes measured by the video camera agreed with the changes detected by conventional methods of monitoring. One of the other findings from this previous study was that the timing and pattern of arrival of pulse/blood flow to different regions of skin does not follow what is known about the anatomical distribution of the larger blood vessels. The sequence by which the skin is perfused is not known, and it is not known whether a general pattern exists which agrees person-to-person. An understanding of this normal pattern may be key to developing a tool which can detect changes in underlying blood flow/heart function by detecting changes in this pattern.

Who can participate?
Healthy men and women aged 18 to 65

What does the study involve?
The normal pattern of blood perfusion is assessed in terms of the sequence and distribution of blood arrival. The researchers will then create changes by giving drugs which will increase and decrease the diameter of blood vessels near the surface of the skin. They will describe the directional changes in perfusion pattern created by these opposite-acting drugs. In the second part of the experiment, the researchers will place a tourniquet to temporarily stop the blood flow into the legs. After 60 seconds, they will deflate the tourniquet and study the sequence in which blood re-fills the leg vessels. This will give an idea of the underlying connection of blood vessels and help create a map of the normal blood perfusion pattern. The study visit will take about 2 hours.

What are the possible benefits and risks of participating?
The participants will be given a £50 voucher for participation. In terms of risks, the participants may experience discomfort during insertion of the drip which will remain in place for the duration of camera recording. The two drugs being used are safe and have been used in heart research in healthy volunteers at higher doses than the researchers intend to use, but may cause increase or decrease in blood pressure, headaches, and breathlessness. In order to minimise the risks, the researchers will be monitoring the participants closely and a dedicated doctor will be present for safety of the participants.

Where is the study run from?
Cardiovascular Clinical Research Facility in the John Radcliffe Hospital, Oxford (UK)

When is the study starting and how long is it expected to run for?
March 2019 to September 2023

Who is funding the study?
Oxford Biomedical Research Centre (UK)

Who is the main contact?
Dr Mirae Harford
mirae.harford@ndcn.ox.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Mirae Harford

ORCID ID

http://orcid.org/0000-0003-2851-1577

Contact details

Kadoorie Centre for Critical Care Research and Education
John Radcliffe Hospital
Oxford
OX3 9DU
United Kingdom
+44 (0)1865223101
mirae.harford@ndcn.ox.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

R63796/RE001

Study information

Scientific title

Optical monitoring of changes in perfusion map of lower limbs compared to traditional haemodynamic monitoring methods in response to pharmacological challenges in healthy volunteers or Mapping Of Lower Limb skIn pErfusion (MOLLIE)

Acronym

MOLLIE

Study hypothesis

1. Changes in peripheral circulation induced by phenylephrine and glyceryl trinitrate can be detected by video-based monitors by tracking changes in the perfusion map of lower limbs (where perfusion map is the chronological order of pulsatile signal arrival to different regions of interest of lower limb skin).
2. Changes in peripheral circulation induced by phenylephrine and glyceryl trinitrate can be detected by video-based monitors by tracking changes in the temperature map of lower limbs.
3. Changes in pulsatile signal of lower limb regions of interest can be used to identify arterial perforator locations.

Ethics approval

Approved 16/07/2019, Medical Sciences Interdivisional Research Ethics Committee (Research Services, University of Oxford, Wellington Square, Oxford, OX1 2JD, UK; Tel: +44 (0)1865 616577; Email: ethics@medsci.ox.ac.uk), ref: R63796/RE001

Study design

Single-centre non-randomised study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Other

Trial type

Other

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Perfusion of lower limbs

Intervention

1. Infusion of phenylephrine to induce peripheral vasoconstriction
2. Infusion of glyceryl trinitrate (GTN) to induce peripheral vasoconstriction
3. Tourniquet application to lower limb followed by tourniquet release

The aim of this study is to describe the normal pattern of blood perfusion in terms of the sequence and distribution of blood arrival. The researchers will then create changes in the cardiovascular state by giving drugs which will increase and decrease the diameter of blood vessels near the surface of the skin. They will describe the directional changes in perfusion pattern created by these opposite-acting drugs.

In the second part of the experiment, the researchers will place a tourniquet to temporarily stop the blood flow into the legs. After 60 seconds, they will deflate the tourniquet and study the sequence in which blood re-fills the leg vessels. This will give an idea of the underlying connection of blood vessels and help create a map of the normal blood perfusion pattern.

Proposed timeline:
00:00 – 00:10 Consent check, measure height/weight/skin colour
00:10 – 00:20 History and examination
00:20 – 00:30 IV cannulation, IV infusion set up
00:30 – 00:40 Positioning in bed, check equipment set up (trial recording), set up reference devices
00:40 Recording starts
00:40 – 00:50 Rest period with no intervention
00:50 – 01:05 15-minute infusion drug 1
01:05 – 01:35 20-minute Washout period
01:35 – 01:50 15-minute infusion drug 2
01:50 – 02:20 20-minute Washout period
02:20 – 02:25 Tourniquet inflation and release
02:25 End of study
Post study: final check, medical review prior to leaving

Intervention type

Other

Phase

Drug names

Primary outcome measure

Skin perfusion pattern at rest and change to the pattern post-exposure to phenylephrine and glyceryl trinitrate (GTN). Measured using composite measures from three different cameras measuring in visible, near-infrared, and infrared spectrum. Measures taken will include the strength of pulsatile signal measured at skin surface, absolute skin colour change when under constant lighting and angle, skin surface temperature gradient from proximal to distal areas, blood flow measurement using laser speckle contrast imager. Measurements will be taken at baseline, at one-minute intervals with increasing dose of phenylephrine and GTN, and at stable infusion maximal dose.

Secondary outcome measures

Chronological order of skin perfusion when lower limb is reperfused following application and removal of a lower limb tourniquet. Measured using the same camera set up as primary outcome measure, across all exposed regions of skin of lower limb (from mid-thigh to mid-shin). Measurements will be taken continuously during the one-minute tourniquet application and in the 5 minutes following tourniquet release.

Overall trial start date

01/03/2019

Overall trial end date

30/09/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Healthy males and females between the ages of 18 to 65

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

30

Participant exclusion criteria

1. Patient whose anatomy, condition, or other required monitoring precludes the use of the camera equipment or thoracic bioimpedance monitor kit. Examples include skin disorders such as eczema, scleroderma or psoriasis
2. Allergy to silver chloride ECG sensors
3. Hyperthyroidism (intravenous phenylephrine contraindicated)
4. Any regular medication except combined oral contraceptives
5. Pregnant or breastfeeding
6. History or current psychiatric illness
7. History or current neurological conditions (e.g. epilepsy)
8. History of cardiovascular disease making phenylephrine or GTN unsafe

Recruitment start date

01/10/2019

Recruitment end date

31/05/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cardiovascular Clinical Research Facility
John Radcliffe Hospital Headley Way
Oxford
OX3 9DU
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Clinical Trials and Research Governance
Joint Research Office
Block 60
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
+44 (0)1865 572221
karl.shepherd@admin.ox.ac.uk

Sponsor type

University/education

Website

https://www.admin.ox.ac.uk/researchsupport/ctrg

Funders

Funder type

Research organisation

Funder name

Oxford Biomedical Research Centre

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

It is anticipated that the project outcome will be written up for peer-reviewed publication with the possibility of being presented in conferences. The results may be shared internally within the department/university, and may be shared on a public website for Kadoorie Centre for Critical Care Research and Education which will be available to the public. The researchers will offer to contact any participants who express an interest in the results with the outcome of the project.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are not expected to be made available as the data from the camera cannot be completely anonymised. In the ethics application this was extensively discussed and it was decided that the dataset will be held in a secure setting behind two doors and restricted access within Kadoorie Centre for Critical Care Research and Education and Institute of Biomedical Engineering secure server.

Intention to publish date

01/09/2021

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

16/08/2019: The recruitment start date was changed from 01/08/2019 to 01/10/2019. 17/07/2019: Trial's existence confirmed by ethics committee.