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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] 284550 0
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 290736 0
Condition category
Condition code
Physical Medicine / Rehabilitation 292177 292177 0 0
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] 289325 0
Not applicable
Comparator / control treatment
Not applicable - Observational study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 292064 0
Serum activin level
Timepoint [1] 292064 0
Daily until discharge from ICU
Primary outcome [2] 293899 0
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] 293899 0
120 hours after admission to ICU
Primary outcome [3] 293900 0
Six-Minute Walk test
Timepoint [3] 293900 0
On acute hospital discharge
Secondary outcome [1] 308115 0
Grip Strength measured with a hand held dynamometer.
Timepoint [1] 308115 0
On awakening; first standing occasion; discharge to ward and discharge from acute hospital.
Secondary outcome [2] 312114 0
Knee extension strength knee measured using Medical Research Council Scale for manual muscle testing.
Timepoint [2] 312114 0
On awakening; first standing occasion; discharge to ward and discharge from acute hospital.
Secondary outcome [3] 312115 0
Timed Up and Go Test.
Timepoint [3] 312115 0
On acute hospital discharge.
Secondary outcome [4] 312116 0
Physical Function in ICU test (PFIT)
Timepoint [4] 312116 0
On first standing occasion and on discharge to ward
Secondary outcome [5] 312118 0
Discharge destination
Timepoint [5] 312118 0
On discharge from acute hospital
Secondary outcome [6] 312119 0
ICU length of stay
Timepoint [6] 312119 0
On discharge from ICU
Secondary outcome [7] 312120 0
Hospital length of stay
Timepoint [7] 312120 0
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?
No
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
36
Accrual to date
Final
36
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 3292 0
Frankston Hospital - Frankston
Recruitment hospital [2] 3294 0
Western Hospital - Footscray
Recruitment postcode(s) [1] 9076 0
3199 - Frankston
Recruitment postcode(s) [2] 9078 0
3011 - Footscray

Funding & Sponsors
Funding source category [1] 290464 0
Hospital
Name [1] 290464 0
Footscray Hospital
Western Health Research Grant
Country [1] 290464 0
Australia
Funding source category [2] 290465 0
Other Collaborative groups
Name [2] 290465 0
Australian Institute for Musculoskeletal Science
Country [2] 290465 0
Australia
Primary sponsor type
Hospital
Name
Footscray Hospital Western Health
Address
Gordon St
Footscray VIC
3011
Country
Australia
Secondary sponsor category [1] 289166 0
None
Name [1] 289166 0
Address [1] 289166 0
Country [1] 289166 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292136 0
Monash Health HREC
Ethics committee address [1] 292136 0
246 Clayton Road
Clayton
Victoria 3168
Ethics committee country [1] 292136 0
Australia
Date submitted for ethics approval [1] 292136 0
23/07/2014
Approval date [1] 292136 0
04/09/2014
Ethics approval number [1] 292136 0
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 44962 0
Dr Elizabeth Skinner
Address 44962 0
Footscray Hospital
Gordon St
Footscray VIC
3011
Country 44962 0
Australia
Phone 44962 0
+61419101708
Fax 44962 0
Email 44962 0
[email protected]
Contact person for public queries
Name 44963 0
Elizabeth Skinner
Address 44963 0
Footscray Hospital
Gordon St
Footscray VIC
3011
Country 44963 0
Australia
Phone 44963 0
+61419101708
Fax 44963 0
Email 44963 0
[email protected]
Contact person for scientific queries
Name 44964 0
Elizabeth Skinner
Address 44964 0
Footscray Hospital
Gordon St
Footscray VIC
3011
Country 44964 0
Australia
Phone 44964 0
+61419101708
Fax 44964 0
Email 44964 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not included in the informed consent form.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
603Informed consent form    365476-(Uploaded-04-12-2018-08-52-31)-Study-related document.docx



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