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Trial registered on ANZCTR


Registration number
ACTRN12616000835448
Ethics application status
Approved
Date submitted
17/06/2016
Date registered
27/06/2016
Date last updated
30/08/2019
Date data sharing statement initially provided
30/08/2019
Date results information initially provided
30/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The GAINS trial - Growth and Anabolism in Intensive Care Survivors
Scientific title
The GAINS trial - a randomised controlled double blind pilot study comparing nandrolone and placebo for muscle weakness in Intensive Care Survivors
Secondary ID [1] 289483 0
None
Universal Trial Number (UTN)
Trial acronym
GAINS trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Intensive Care 299168 0
Critical illness myopathy 299169 0
Critical illness malnutrition 299170 0
Condition category
Condition code
Physical Medicine / Rehabilitation 299183 299183 0 0
Other physical medicine / rehabilitation
Diet and Nutrition 299216 299216 0 0
Other diet and nutrition disorders
Musculoskeletal 299217 299217 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomized controlled trial: placebo versus nandrolone administration.

Intervention arm: Nandrolone intramuscular injection (IMI) administered weekly for 3 weeks.
Dose 100mg females, 200mg males

Intervention will be administered by blinded investigators to inpatients so adherence will not be a problem.
Intervention code [1] 295070 0
Treatment: Drugs
Comparator / control treatment
Sterile water for injection IMI.

Both placebo and study drug will be prepared in masked syringes so contents not apparent to person administering.
Control group
Placebo

Outcomes
Primary outcome [1] 298667 0
Change in muscle strength measured by:
1) grip strength (handheld dynamometry)
Timepoint [1] 298667 0
Weekly from time of first dose to day after last dose or discharge from hospital
Primary outcome [2] 298698 0
2) medical research council muscle strength sum score
Timepoint [2] 298698 0
Weekly from time of first dose to day after last dose or discharge from hospital
Primary outcome [3] 298699 0
3) functional activity level using Chelsea critical care physical assessment tool (CPAx)
Timepoint [3] 298699 0
Weekly from time of first dose to day after last dose or discharge from hospital
Secondary outcome [1] 324892 0
Body weight change as measured by calibrated bed scale or digital scale
Timepoint [1] 324892 0
Weekly from time of first dose to day after last dose or discharge from hospital
Secondary outcome [2] 324893 0
ICU length of stay (using patient medical records)
Timepoint [2] 324893 0
Assessed at discharge from ICU
Secondary outcome [3] 324894 0
Serum albumin
Timepoint [3] 324894 0
Weekly from time of first dose to day after last dose or discharge from hospital
Secondary outcome [4] 324895 0
Serum Haemoglobin
Timepoint [4] 324895 0
Weekly from time of first dose to day after last dose or discharge from hospital
Secondary outcome [5] 324999 0
Mid arm circumference (MUAC is the circumference of the left upper arm, measured at the mid-point between the tip of the shoulder and the tip of the elbow (olecranon process and the acromium))
Timepoint [5] 324999 0
Weekly from time of first dose to day after last dose or discharge from hospital
Secondary outcome [6] 325000 0
Quadriceps muscle layer thickness as measured by ultrasound (measured at the border between the lower third and upper two-thirds between the ASIS and the upper pole of the patella, as well as the measurement of the midpoint between the ASIS and the upper pole of the patella. The right and left quadriceps value assessed was the average of these four readings over the right and left legs (two at each site) see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502435/)
Timepoint [6] 325000 0
Weekly from time of first dose to day after last dose or discharge from hospital.
Secondary outcome [7] 325095 0
Hospital length of stay (using patient medical records)
Timepoint [7] 325095 0
Assessed at discharge from hospital

Eligibility
Key inclusion criteria
Admitted To Intensive Care Unit or High Dependency Unit
Significant weakness as result of ICU stay or pre-ICU condition as deemed by the treating clinician
Weight loss (BMI < 20 or >10% weight loss in last 6 months)
Receiving nutritional inputs at estimated goals for at least 3 days
Minimum age
21 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Intercurrent septic shock (infection + vasopressors)
Prostate or breast cancer
Active cardiac disease (STEMI/NSTEMI last 2 weeks) or EF < 35%
Ongoing non-curable reason for catabolic state (such as active malignancy, HIV with opportunistic infection in last 2 months, inadequate nutritional intake)
Unable to engage in rehabilitation (due to significant neurological or orthopaedic issues)
Normal age related level of serum testosterone
Pregnancy or breast feeding
Any known allergies to nandrolone components (peanuts, soya, latex)
Elevated LFTS (ALT > 5 x normal) and impaired bilirubin excretion
Nephrotic syndrome (>3 g proteinuria/day

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment by numbered containers containing prepared syringes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
The investigational pharmacist will not be blinded, but will not be involved in administering,assessing outcomes or analysis.
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
This is a pilot study and thus a power analysis is not possible.
Differences in end points are exploratory.
Means and standard deviations will be calculated for age, height, weight.
Primary outcomes will be tested using independent sample t tests
Non-parametric tests will be used where results are not normally distributed.
Chi square tests will be used for categorical variables.
Efficacy of intervention will be analysed on an intention to treat basis.
Baseline variables will be recorded to demontrate that the groups are comparable, if this is not demonstrated, post-hoc adjustmets to correct for differences will be applied.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 5996 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 5997 0
Royal Perth Hospital - Perth

Funding & Sponsors
Funding source category [1] 293846 0
Hospital
Name [1] 293846 0
Sir Charles Gairdner Hospital, Intensive Care Research Fund
Address [1] 293846 0
Intensive Care Department
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands 6009, WA
Country [1] 293846 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital
Address
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands 6009 WA
Country
Australia
Secondary sponsor category [1] 292684 0
None
Name [1] 292684 0
Address [1] 292684 0
Country [1] 292684 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295274 0
Sir Charles Gairdner Human Research Ethics Committee
Ethics committee address [1] 295274 0
Hospital Avenue
Nedlands 6009 WA
Ethics committee country [1] 295274 0
Australia
Date submitted for ethics approval [1] 295274 0
24/05/2016
Approval date [1] 295274 0
26/07/2016
Ethics approval number [1] 295274 0

Summary
Brief summary
ICU acquired weakness, the result of catabolism, immobility and critical illness polymyoneuropathy is of significant consequence to long-stay ICU patients. Recent advances have tried to prevent ICU acquired weakness by early mobilisation of patients and optimising nutrition. The loss of lean body mass in critical illness is also associated with misalignment between catabolic and anabolic hormones. One potential treatment may be to provide anabolic support in the recovery phase from prolonged critical illness.

Nandrolone is a synthetic anabolic steroid that has greater anabolic (growth) and less androgenic (masculinizing) properties than testosterone. It has previously been used successfully in patients with weight loss in HIV/AIDS, and muscle wasting in patients with chronic obstructive pulmonary disease and end stage renal failure.

This is a pilot multicentre randomized placebo controlled trial that will look at the effects of nandrolone given weekly for three weeks, versus placebo, in patients who have lost significant amounts of weight or strength while in the ICU. Our primary outcome will be changes in muscle strength, but we will also be looking for changes in weight and length of stay.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66738 0
Dr Matthew Anstey
Address 66738 0
Intensive Care Department
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands WA 6009
Country 66738 0
Australia
Phone 66738 0
+61893461010
Fax 66738 0
Email 66738 0
matthew.anstey@health.wa.gov.au
Contact person for public queries
Name 66739 0
Dr Matthew Anstey
Address 66739 0
Intensive Care Department
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands WA 6009
Country 66739 0
Australia
Phone 66739 0
+61893461010
Fax 66739 0
Email 66739 0
matthew.anstey@health.wa.gov.au
Contact person for scientific queries
Name 66740 0
Dr Matthew Anstey
Address 66740 0
Intensive Care Department
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands WA 6009
Country 66740 0
Australia
Phone 66740 0
+61893461010
Fax 66740 0
Email 66740 0
matthew.anstey@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Confidentiality of data cf ethics approval.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary