Condition category
Musculoskeletal Diseases
Date applied
22/05/2015
Date assigned
08/07/2015
Last edited
08/07/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Intensive care unit (ICU) patients are more likely to survive today than a decade ago, however they continue to suffer damage to their muscles that leads to long term weakness despite advances in treatment. Muscle injury in ICU patients is characterised by reduced muscle fibre size, areas of muscle cell death, fluid retention (oedema), and general muscle wasting. This leads to profound weakness, a reduction in muscle cross-sectional area and alterations in the graininess (echogenicity) of ultrasound pictures. Various treatments (including drugs, nutrition, and physiotherapy) aimed at preventing muscle damage have been tested in clinical studies but none have led to long term improvements in physical function. It’s still not known which treatments can prevent or treat ICU-related muscle injury, or when to apply these treatments so that they are most effective. This is because the changes in structure, volume and function of skeletal muscle in response to critical illness are not fully understood. It’s also not understood how these characteristics change over time. Also, it’s not known how damaged muscle responds to therapies, such as physiotherapy, over time. Finally, the measurements used to measure changes in muscle characteristics in response to treatment are not very precise. Studies of the muscles of ICU patients have so far used clinical assessment, ultrasound, and muscle biopsy. Successful clinical assessment of muscle function relies on patient cooperation and self-reporting, which prevents accurate assessment of muscle function in isolation of other external factors. Ultrasound is unable to differentiate between muscle fat and water, and this makes measurement of muscle volume unreliable. Finally, muscle biopsy is reliant on sampling the correct part of the muscle. Magnetic resonance imaging (MRI) has emerged as a potentially useful tool in the assessment and tracking of ICU-related muscle injury. MRI techniques allow assessment of changes in muscle volume that has not been possible using other methods. This study of ICU survivors with weak muscles, ICU survivors with strong muscles, and a control group of healthy post-surgical patients will use some established MRI techniques, in addition to some new MRI techniques, to provide detailed information on the structure and function of muscles in recovering ICU patients. The aim of this study is to identify differences in the muscles that will allow clinicians to predict how patients will recover after ICU, and also to identify dynamic changes in the muscle that might allow the recovery of muscle injury to be tracked.

Who can participate?
Adult ICU survivors who are expected to make a poor physical recovery, those expected to make a good physical recovery and healthy adults who have undergone surgery.

What does the study involve?
Participants are non-randomly allocated into one of three groups. Those in group 1 (intervention group) are adult ICU survivors expected to make a poor physical recovery. Those in group 2 (intervention group) are adult ICU survivors expected to make a good physical recovery. Those in group 3 (control group) are healthy adults who are matched by age, gender and body mass index (BMI) to participants in group 1 and 2. All participants undergo various tests in order to obtain detailed information about the structure and function of their muscles. The tests used include MRI, 2D ultrasound imaging, various clinical assessments and blood tests. For participants in group 1, measurements are taken at the start of the study and again 3 months later. For participants in group 2 and 3, measurements are taken at the start of the study only.

What are the possible benefits and risks of participating?
Participating patients will be transferred to an MRI scanner during the first 7 days of ICU discharge. Patients at this stage are likely to be clinically stable, however, it is possible that they are unstable and so an assessment will be carried out by research nurses, and if necessary medical staff prior to transfer and scans deferred or cancelled if the transfer will pose undue risk to the patient. Some discomfort is expected due to prolonged MRI scanning, as this can take longer than other types of scan. Discomfort is minimal but may become tiresome if prolonged. Discomfort will be minimised by a research nurse (or doctor) escort who will be there to ensure that if the patient experiences discomfort, the study can be terminated. Furthermore the duration of scanning will be limited to less than 1 hour which should be tolerable for most patients. For the healthy controls, and those patients that are returning some months after an ICU stay, the study will involve a return visit to the hospital. Refreshments will be provided, and taxi transport provided to ensure that this does not put the patient out unduly. Blood samples will be taken by venepuncture, a low risk procedure that can be uncomfortable and cause localised bleeding. There is a low risk of other complications (inadvertent arterial puncture, nerve damage, infection).

Where is the study run from?
1. Royal Infirmary of Edinburgh (UK)
2. University of Edinburgh (UK)

When is the study starting and how long is it expected to run for?
October 2014 to August 2016

Who is funding the study?
Edinburgh Critical Care Research Group (UK)

Who is the main contact?
1. Ms D Campbell
2. Dr D Griffith

Trial website

Contact information

Type

Public

Primary contact

Ms Dawn Campbell

ORCID ID

Contact details

Royal Infirmary of Edinburgh
Department of Anaesthesia
Critical Care & Pain Medicine
Room S8208
2nd Floor
51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom

Type

Scientific

Additional contact

Dr David Griffith

ORCID ID

http://orcid.org/0000-0001-9500-241X

Contact details

Royal Infirmary of Edinburgh
Department of Anaesthesia
Critical Care & Pain Medicine
Room S8210
2nd Floor
51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

0.2

Study information

Scientific title

A pilot observational study to investigate the structure and function of skeletal muscle in survivors of critical illness using magnetic resonance imaging (MRI)

Acronym

IC Muscle

Study hypothesis

Objectives:
1. To test the feasibility and tolerability of MRI imaging as a method of assessment of critical illness-induced muscle lesions
2. To establish MRI protocols for the assessment of injury and rehabilitation from critical illness induced muscle injury
3. To compare skeletal muscle volume between ICU survivors and healthy controls
4. To compare the viscoelastic properties of ICU survivors with healthy controls
5. To assess the presence or absence of focal skeletal muscle necrosis and fibrosis in ICU patients with significant clinical muscle weakness using MRI
6. To assess whether ultrasound measurements of skeletal muscle correlate with MRI findings in patients with significant weakness after critical illness
7. To assess whether MRI measurements correlate with clinical assessment of physical function
8. To test the association between inflammation (CRP concentration) and MRI appearances of muscle injury in ICU survivors

Ethics approval

South East Scotland Research Ethics Committee 2, 14/04/2015, ref: 15-SS-0056.

Study design

Pilot observational study

Primary study design

Observational

Secondary study design

Case-control study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

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

Condition

Intensive care unit acquired weakness

Intervention

The skeletal muscle of survivors of critical illness will be studied using 3 broad approaches:
1. Magnetic resonance imaging (MRI)
2. 2D ultrasound imaging
3. Clinical assessment (quadricpes dynamometry; Medical Research Council sum-score of global muscle strength; 6 minute walk test)
4. Blood samples will be drawn for serological analysis

Intervention type

Other

Phase

Drug names

Primary outcome measures

For group 1 all measurements will be taken at baseline and 3 months; for groups 2 and 3 all measurements will be taken at baseline only:
1. Quadriceps muscle volume.

Secondary outcome measures

For group 1 all measurements will be taken at baseline and 3 months; for groups 2 and 3 all measurements will be taken at baseline only:
1. Qualitative assessment of muscle oedema and focal inflammation
2. Relative fat fraction (measured by the three-point Dixon method)
3. Mean elasticity (measured in KPa using magnetic resonance elastography)
4. Quadriceps strength (quadriceps dynamometry)

Overall trial start date

30/10/2014

Overall trial end date

31/08/2016

Reason abandoned

Eligibility

Participant inclusion criteria

Group 1 (10 patients):
1. Adult ICU survivors
2. Ventilated for 48 hours or more
3. Good level of physical function prior to hospital admission (Rivermead Mobility Index (RMI) >/14 at any time in the week prior to hospital admission)
4. Within 7 days of ICU discharge
5. Evidence of very poor physical recovery (RMI ≤8)
Group 2 (10 patients):
1. Adult ICU survivors
2. Paired by age, gender and body mass index (BMI) to Group 1
3. Ventilated for 48 hours or more
4. Good level of physical function prior to hospital admission (RMI =15 at any time in the week prior to hospital admission)
5. Within 7 days of ICU discharge
6. Evidence of very good physical recovery (RMI ≥ 9)
Group 3 (10 patients):
1. A healthy community based sample derived from patients presenting for day case surgery.
2. Paired by age, gender, and BMI to groups 1 and 2
3. Good level of physical function (RMI = 15)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

30

Participant exclusion criteria

Exclusion criteria for groups 1 and 2:
1. <18 years of age
2. Patient receiving palliative care
3. Patient has a contraindication to MRI imaging
4. Neurological diagnosis
5. Background chronic neuromuscular disease
6. Patient lacks mental capacity
7. Malignancy
8. Chronic inflammatory disease
9. Clinical instability
Exclusion criteria for group 3
1. <18 years
2. Malignancy
3. Chronic inflammatory disease
4. Background chronic neuromuscular disease
5. Neurological diagnosis
6. Presenting for lower limb arthroplasty
7. Patient lacks mental capacity

Recruitment start date

01/06/2015

Recruitment end date

31/05/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Infirmary of Edinburgh
51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom

Trial participating centre

University of Edinburgh
Clinical Research Imaging Centre (CRIC) 47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom

Sponsor information

Organisation

University of Edinburgh

Sponsor details

Research & Development Management Suite
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom

Sponsor type

University/education

Website

www.ed.ac.uk

Organisation

NHS Lothian

Sponsor details

Research & Development Management Suite
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Edinburgh Critical Care Research Group

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

We intend to publish the research in a peer reviewed critical care journal by December 2016.

Intention to publish date

01/12/2016

Participant level data

Stored in repository

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes