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Trial registered on ANZCTR


Registration number
ACTRN12620000776909
Ethics application status
Approved
Date submitted
12/06/2020
Date registered
30/07/2020
Date last updated
30/07/2020
Date data sharing statement initially provided
30/07/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
PROtein dose and Muscle Synthesis in critically ill patients (PROMS)
Scientific title
PROtein dose and Muscle Synthesis in critically ill patients (PROMS)
Secondary ID [1] 301168 0
Nil
Universal Trial Number (UTN)
Trial acronym
PROMS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical Illness 317294 0
Intensive Care Nutrition 318135 0
Condition category
Condition code
Diet and Nutrition 315415 315415 0 0
Other diet and nutrition disorders
Oral and Gastrointestinal 315534 315534 0 0
Normal oral and gastrointestinal development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Increased protein delivery is recommended during critical illness, yet there is little understanding on how the body handles protein during critical illness. Given this, our study aims to understand whether the ability of critically ill patients to utilise amino acids is dependent on the amount of amino acids available (e.g. the dose of protein provided). This is a prospective, single-centre, parallel-group, interventional study, where critically ill patients will be randomised into receiving either 20g or 40g of protein. The study will be recruiting patients who are admitted to the Intensive Care Unit at the Royal Adelaide Hospital (RAH), South Australia. All patients will be studied on one occasion only.

Following informed consent from patient's next of kin, a post-pyloric feeding tube will be inserted. Patients will undergo a 4 hour fast (no enteral feeds) prior to study commencement. The plasma phenylalanine and tyrosine pool will be primed with a single intravenous dose of L-ring-[13C6] phenylalanine (2.25 µmol/kg) and L-[3,5-2H2]-tyrosine (0.867 µmol/kg), followed by continuous intravenous infusion of these two tracers for the whole study day (10 hours). Following 3.5 hours from the start of IV tracer infusion, an intra-duodenal infusion of protein (20g or 40g diluted to 240ml with water) enriched with L-ring-[13C6] phenylalanine will be delivered to the patient over 60 mins. The intervention will be provided by research staff and documented on the Case Report Form. Blood samples and muscle biopsies (from the middle region of the vastus lateralis muscle) will be collected at pre-determined time points. At study completion, the enteral feeds be will recommenced.

Tracer infusions will be prepared by the hospital pharmacy department to ensure dosing accuracy and safety precautions. Muscle biopsies will be conducted by trained intensive care physicians.
Intervention code [1] 317483 0
Treatment: Other
Comparator / control treatment
20g protein diluted to 240ml with water enriched with L-ring-[13C6] phenylalanine will be delivered to the patient over 60 mins.
Control group
Dose comparison

Outcomes
Primary outcome [1] 323679 0
Fractional synthesis rate (FSR in %/h) of post-prandial mixed muscle protein (obtained from muscle biopsies) in critically ill patients receiving 40g protein compared to 20g protein.
Timepoint [1] 323679 0
Post-prandial muscle fractional synthesis rate will be determined from muscle biopsies taken at t=0 and t=360 mins.
Secondary outcome [1] 382560 0
Basal muscle protein fractional synthesis rate.
Timepoint [1] 382560 0
Basal muscle protein fractional synthesis rate will be determined from muscle biopsy samples at -120 and 0 mins.
Secondary outcome [2] 382573 0
Area under the plasma amino acid concentration time curve
Timepoint [2] 382573 0
Amino acid concentration will be measured post IV priming dose (at -210, -120, -60, -30, 0 mins) and post intraduodenal administration of either 20g or 40g of protein (at 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, 360 mins).
Secondary outcome [3] 382584 0
Whole body protein breakdown will be determined from plasma samples obtained at the specified time points.
Timepoint [3] 382584 0
Pre-prandial (at -210, -120, -60, -30, 0 mins) and post-prandial (at 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, 360 mins)
Secondary outcome [4] 382585 0
Whole body protein balance will be determined from plasma samples obtained at the specified time points.
Timepoint [4] 382585 0
Pre-prandial (at -210, -120, -60, -30, 0 mins) and post-prandial (at 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, 360 mins)
Secondary outcome [5] 382829 0
Plasma enrichments (in MPE) of L-[ring-13C6]-phenylalanine and L-[3,5-2H2]-tyrosine
Timepoint [5] 382829 0
-210, -120, -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, 360 mins.
Secondary outcome [6] 382830 0
Area under the concentration time curves of glucose concentration analysed via glucose oxidase method.
Timepoint [6] 382830 0
-210, -120, -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, 360 mins.
Secondary outcome [7] 382881 0
Area under the concentration time curve of insulin concentration analysed via radioimmunoassay technique.
Timepoint [7] 382881 0
-210, -120, -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, 360 mins.
Secondary outcome [8] 382882 0
Area under the concentration time curves of cholecystokinin concentration analysed via radioimmunoassay technique.
Timepoint [8] 382882 0
-210, -120, -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, 360 mins.
Secondary outcome [9] 382883 0
Area under the concentration time curves of peptide YY concentration analysed via radioimmunoassay technique.
Timepoint [9] 382883 0
-210, -120, -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, 360 mins.
Secondary outcome [10] 382884 0
Area under the concentration time curve of ghrelin concentration analysed via radioimmunoassay technique.
Timepoint [10] 382884 0
-210, -120, -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, 360 mins.

Eligibility
Key inclusion criteria
Inclusion:
*Adults (18 years of age and above)
*Admitted to the intensive care unit at the Royal Adelaide Hospital
*Mechanically ventilated and expected to remain ventilated until the day after recruitment
*Suitable for enteral feeding
*Arterial line in situ
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusions:
*Recent upper abdominal surgery
*Vegan
*Lactose intolerance
*Any order to withhold active treatment
*Jehovah’s Witness
*Pregnancy
*Receiving dialysis
*For muscle biopsy: Bleeding diathesis (INR > 2; APTT > 50, platelets < 50) including those receiving anticoagulants (other than low dose for DVT prophylaxis) and anti-platelet agents

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 of patients to either group will not be concealed from the investigators, however the external lab analysing the samples will be blinded to group allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated sequence
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
Based on the observed variability from the previous studies, a standard deviation for FSR of 0.0124 %/h is assumed. To detect a difference between groups of 0.0164 %/h, with 80% power and at 5% significance level (effect size = 1.3), 10 patients per group will be required.

Recruitment
Recruitment status
Not yet 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)
SA
Recruitment hospital [1] 16600 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 30197 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 305612 0
Government body
Name [1] 305612 0
National Health and Medical Research Council
Address [1] 305612 0
16 Marcus Clarke St,
Canberra ACT 2601
Country [1] 305612 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Royal Adelaide Hospital,
Port road, Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 306134 0
None
Name [1] 306134 0
Address [1] 306134 0
Country [1] 306134 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305908 0
Central Adelaide Local Health Network Human Research Ethics Committee (CALHN HREC)
Ethics committee address [1] 305908 0
Level 3, Roma Mitchell House
136 North Terrace, Adelaide SA 5000
Ethics committee country [1] 305908 0
Australia
Date submitted for ethics approval [1] 305908 0
03/03/2020
Approval date [1] 305908 0
25/06/2020
Ethics approval number [1] 305908 0
12960

Summary
Brief summary
Critically ill patients receive inadequate nutrition, potentially contributing to muscle wasting and reduced physical function in the long term. Increased protein delivery is recommended during critical illness with the intent of maintaining muscle mass, but there is little understanding on how the body handles protein during critical illness. This study is aimed at understanding whether the ability of critically ill patients to use dietary protein to build muscle is dependent on the amount of amino acids provided. Critically ill patients will be recruited from the Intensive Care Unit at the Royal Adelaide Hospital and randomised to receive either 20g or 40g of protein. The amount of muscle protein synthesis that occurs following these protein doses will be measured.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102022 0
Dr Tejaswini Arunachala Murthy
Address 102022 0
Intensive Care Unit,
Royal Adelaide Hospital,
Port road, Adelaide, SA 5000
Country 102022 0
Australia
Phone 102022 0
+61 449097998
Fax 102022 0
Email 102022 0
drpadminimurthy@gmail.com
Contact person for public queries
Name 102023 0
Dr Tejaswini Arunachala Murthy
Address 102023 0
Intensive Care Unit,
Royal Adelaide Hospital,
Port road, Adelaide, SA 5000
Country 102023 0
Australia
Phone 102023 0
+61 449097998
Fax 102023 0
Email 102023 0
drpadminimurthy@gmail.com
Contact person for scientific queries
Name 102024 0
Dr Lee-anne Chapple
Address 102024 0
Intensive Care Unit,
Royal Adelaide Hospital,
Port road, Adelaide, SA 5000
Country 102024 0
Australia
Phone 102024 0
+61 8 7074 1763
Fax 102024 0
Email 102024 0
lee-anne.chapple@adelaide.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Patient confidentiality.
What supporting documents are/will be available?
No other documents available
Summary results
No Results