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Trial registered on ANZCTR

Registration number

ACTRN12615000047594

Ethics application status

Approved

Date submitted

21/12/2014

Date registered

21/01/2015

Date last updated

11/12/2019

Date data sharing statement initially provided

4/12/2018

Type of registration

Prospectively registered

Titles & IDs

Public title

Serum activin, gene expression, muscle mass and function in people with critical illness (SAGE-MUSCLE): an observational cohort study

Scientific title

Serum activin, gene expression, muscle mass and function in people with critical illness (SAGE-MUSCLE): an observational cohort study

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1156-4189

Trial acronym

SAGE-MUSCLE

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Intensive Care Unit Aquired Weakness

Condition category

Condition code

Physical Medicine / Rehabilitation

Physiotherapy

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

Observation of gene expression, serum activin levels, muscle mass and function in patients who have invasive mechanincal ventilation for at lease 48 hours and are expected to be in intensive care unit for 120 hours. Gene expression will be measured once on day 5 of ICU admission. Serum activin will be measured daily while the patient is in ICU. Muscle mass will be measured once on discharge from acute hospital. Muscle function will be measured at 4 time points: on awakening, first standing occasion, discharge from ICU, discharge from acute hospital.

Intervention code [1]

Not applicable

Comparator / control treatment

Not applicable - Observational study

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Serum activin level

Timepoint [1]

Daily until discharge from ICU

Primary outcome [2]

Needle muscle biopsy of the quadriceps with ultrasound guidance will be required to allow extraction of RNA. Target genes will be analysed by reverse transcription polymerase chain reaction (RT-PCR).

Timepoint [2]

120 hours after admission to ICU

Primary outcome [3]

Six-Minute Walk test

Timepoint [3]

On acute hospital discharge

Secondary outcome [1]

Grip Strength measured with a hand held dynamometer.

Timepoint [1]

On awakening; first standing occasion; discharge to ward and discharge from acute hospital.

Secondary outcome [2]

Knee extension strength knee measured using Medical Research Council Scale for manual muscle testing.

Timepoint [2]

On awakening; first standing occasion; discharge to ward and discharge from acute hospital.

Secondary outcome [3]

Timed Up and Go Test.

Timepoint [3]

On acute hospital discharge.

Secondary outcome [4]

Physical Function in ICU test (PFIT)

Timepoint [4]

On first standing occasion and on discharge to ward

Secondary outcome [5]

Discharge destination

Timepoint [5]

On discharge from acute hospital

Secondary outcome [6]

ICU length of stay

Timepoint [6]

On discharge from ICU

Secondary outcome [7]

Hospital length of stay

Timepoint [7]

On discharge from acute hospital

Eligibility

Key inclusion criteria

Have invasive mechanical ventilation for at least 48 hours and;
Are expected to be in ICU for at least 120 hours

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Aged < 18;
They have a proven or suspected acute primary neurological process likely to result in global impairment of conscious level/cognition or prolonged weakness or;
Death is deemed imminent or inevitable.

Study design

Purpose

Screening

Duration

Cross-sectional

Selection

Defined population

Timing

Prospective

Statistical methods / analysis

Descriptive statistics will be used to describe observations and frequency data and analysed according to normality of distribution (tested via Kolmogorov-Smirnov test) with subsequent parametric or non-parametric equivalent tests chosen as appropriate. Exploratory graphical analyses of serum activin levels; gene expression and muscle mass/function trends will be conducted where appropriate.
Associations between activin levels and gene expression analyses with physical strength outcomes will be investigated using latent growth curve analysis using AMOS version 19. By using latent growth curve analysis, we will be investigating the change in physical strength and how this relates to changes in either activin or gene expression. Using this analysis approach, a pilot sample size of 20 will allow pilot analysis associations between activin levels and physical strength. Future funding will be sought to test a total sample size of 80, which will provide 85% power to detect associations between activin levels and physical strength of effect size =0.50 assuming a mean of 5 assessment points. Patient numbers for gene expression analyses are pilot and will be used to source additional funding if proof-of-concept exists

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

31/01/2015

Actual

6/02/2017

Date of last participant enrolment

Anticipated

31/12/2018

Actual

9/09/2018

Date of last data collection

Anticipated

Actual

9/12/2018

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Frankston Hospital - Frankston

Recruitment hospital [2]

Western Hospital - Footscray

Recruitment postcode(s) [1]

3199 - Frankston

Recruitment postcode(s) [2]

3011 - Footscray

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Footscray Hospital
Western Health Research Grant

Address [1]

Footscray Hospital
Gordon St
Footscray VIC
3011

Country [1]

Australia

Funding source category [2]

Other Collaborative groups

Name [2]

Australian Institute for Musculoskeletal Science

Address [2]

Western Centre for Health Research and Education
Sunshine Hospital
176 Furlong Road St Albans, VIC 3021

Country [2]

Australia

Primary sponsor type

Hospital

Name

Footscray Hospital Western Health

Address

Gordon St
Footscray VIC
3011

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Monash Health HREC

Ethics committee address [1]

246 Clayton Road
Clayton
Victoria 3168

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

23/07/2014

Approval date [1]

04/09/2014

Ethics approval number [1]

HREC/14/SHA/26

Summary

Brief summary

Intensive Care Unit (ICU) services cost the Australian economy at least $1.1 billion annually, excluding the cost of longterm morbidity. In particular, patients with a long length of stay in ICU (> 10-14 days) consume a disproportionate amount of resources. A quarter of these patients suffer a severe weakness syndrome defined as ICU-acquired weakness (ICUAW).
This catastrophic syndrome results in significant limitations to people being able to perform their usual activities required for living (e.g. standing, walking, brushing teeth, showering, toileting or feeding themselves). People who suffer ICU acquired weakness are more likely to die and experience worse physical function and quality of life up to ten years following their ICU admission.
The specific cell level interactions that influence this weakness syndrome are yet to be fully understood. The protein activin limits muscle growth and causes severe muscle wasting. It has recently been shown to not only have strong regulatory effects on muscle mass in mice with cancer, and when blocked, beneficial effects such as reversal of muscle loss. It is known that blood activin levels are significantly higher in people with critical illness who have infection, however the effect this has on muscle mass and weakness has not been established in this setting.
There is also emerging evidence that there may be differences in the genes that turn on and off in people within the first 5 days of an ICU stay. It is logical that genes might also turn on and off differently in people who develop severe weakness in ICU compared to those who don‘t. However no studies have looked at differences in these gene patterns and compared them with changes in weakness or the ability to breathe independently.
The project will compare levels of the protein activin and gene expression patterns (i.e. differences in genes turning on and off) in people admitted to the ICU with and without severe weakness. The investigators will also test muscle strength and the ability of the patient to do functional tasks (e.g. stand up, walk) and the project aims to provide proof-of-concept of an association between protein and gene measurements with muscle strength and function in ICU patients. the results will be used to design future projects investigating i) mechanisms associated with the development of clinically significant weakness and possible therapeutic pathways and ii) prevention strategies to reduce exposure to agents associated with severe weakness in ICU.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Elizabeth Skinner

Address

Footscray Hospital
Gordon St
Footscray VIC
3011

Country

Australia

Phone

+61419101708

Fax

[email protected]

Contact person for public queries

Name

Elizabeth Skinner

Address

Footscray Hospital
Gordon St
Footscray VIC
3011

Country

Australia

Phone

+61419101708

Fax

[email protected]

Contact person for scientific queries

Name

Elizabeth Skinner

Address

Footscray Hospital
Gordon St
Footscray VIC
3011

Country

Australia

Phone

+61419101708

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Not included in the informed consent form.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
603	Informed consent form					365476-(Uploaded-04-12-2018-08-52-31)-Study-related document.docx

Results publications and other study-related documents

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No additional documents have been identified.

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