The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12616001652460
Ethics application status
Approved
Date submitted
25/11/2016
Date registered
30/11/2016
Date last updated
19/07/2019
Date data sharing statement initially provided
19/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Protein absorption in critical illness
Scientific title
To determine if critical illness impairs protein absorption compared to health
Secondary ID [1] 290627 0
NIL
Universal Trial Number (UTN)
Trial acronym
PACE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critically ill 301133 0
Protein absorption 301137 0
Condition category
Condition code
Diet and Nutrition 300900 300900 0 0
Other diet and nutrition disorders
Oral and Gastrointestinal 300901 300901 0 0
Normal oral and gastrointestinal development and function

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Each subject/patient will be studied on one occasion only. Following consent a small intestinal feeding catheter will be inserted using the Cortrak device by a trained research dietitian or intensive care physician. Patients and healthy subjects will undergo an overnight fast (no food or fluid, including water) from midnight until study commencement. The plasma phenylalanine and leucine pool will primed for 2.5 hours with a single intravenous dose of d5-phenylalanine (2.2 ug/kg), L-[3,5-D2]-tyrosine (0.674 ug/kg) and L-[1-13C]-leucine (0.110 ug/kg), after which a intraduodenal infusion for 1 hour of L-[1-13C]phenylalanine-labelled and L-[1-13C]-leucine casein milk protein will be commenced (25 g, 100 kcal, 1.7 kcal/min). Following this a continuous IV infusion of 5 hours of the tracers d5-phenylalanine (0.055 umol/kg/min), L-[3,5-D2]-tyrosine (0.017 umol/kg/min) and L-[1-13C]-leucine (0.110 umol/kg/min) will be administered. At study completion, healthy subjects will be provided with a buffet meal, and enteral feeds will be recommenced in ICU patients.

Protein infusions will be prepared by the hospital pharmacy department to ensure dosing accuracy and safety precautions. Administration of infusions will be by trained intensive care research practitioners.
Intervention code [1] 296502 0
Not applicable
Comparator / control treatment
The study will recruit 15 ICU patients and 10 healthy control volunteers. The volunteers will receive identical treatment to those with critical illness
Control group
Active

Outcomes
Primary outcome [1] 300311 0
Rate and extent of labelled phenylalanine absorption. This is a composite primary outcome assessed by the rate of appearance and disappearance of phenylalanine from the ingested protein compared with the body stores (i.e. exogenous and endogenous phenylalanine rate of appearance). This is assessed through analysis of tracer levels in the blood samples.
Timepoint [1] 300311 0
Blood samples taken prior to IV priming dose (-180 min, -60 min and -30 min). Then at time point 0, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360.

Primary outcome [2] 300326 0
Rate and extent of labelled leucine absorption. This is a composite primary outcome assessed by the rate of appearance and disappearance of leucine from the ingested protein compared with the body stores (i.e. exogenous and endogenous leucine rate of appearance). This is assessed through analysis of tracer levels in the blood samples.
Timepoint [2] 300326 0
Blood samples taken prior to IV priming dose (-180 min, -60 min and -30 min). Then at time point 0, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360.

Secondary outcome [1] 329664 0
Amino acid concentrations
Timepoint [1] 329664 0
Prior to IV priming dose (-180 min, -60 min and -30 min). Then at time point 0, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360. Plasma amino acids will be determined by stable isotope dilution tandem mass spectrometry.
Secondary outcome [2] 329665 0
Fractional synthetic rate (FSR) of mixed muscle protein
Timepoint [2] 329665 0
Prior to IV priming dose and at the commencement of the 6 hour continuous IV infusion. Measured via muscle biopsy. Muscle biopsies taken at 0 min and 360 min. Local anaesthetic will be injected and using a Bergstrom needle a small muscle biopsy (~55mg) will be collected from the middle region of the vastus lateralis muscle at 0 and 360min.
Secondary outcome [3] 329691 0
Glucose concentrations. Blood glucose will be determined immediately by the glucose oxidase method, with accuracy confirmed by the hexokinase technique at predefined time points.
Timepoint [3] 329691 0
Prior to IV priming dose (-180 min, -60 min and -30 min). Then at time point 0, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360.
Secondary outcome [4] 329692 0
Glucagon concentrations. Measured from blood samples by radioimmunoassay using commercially available antibodies
Timepoint [4] 329692 0
Prior to IV priming dose (-180 min, -60 min and -30 min). Then at time point 0, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360.
Secondary outcome [5] 329693 0
CCK concentrations. Measured from blood samples by radioimmunoassay using commercially available antibodies
Timepoint [5] 329693 0
Prior to IV priming dose (-180 min, -60 min and -30 min). Then at time point 0, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360.
Secondary outcome [6] 329694 0
PYY concentrations. Measured from blood samples by radioimmunoassay using commercially available antibodies
Timepoint [6] 329694 0
Prior to IV priming dose (-180 min, -60 min and -30 min). Then at time point 0, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360.
Secondary outcome [7] 329695 0
Ghrelin concentrations. Measured from blood samples by radioimmunoassay using commercially available antibodies
Timepoint [7] 329695 0
Prior to IV priming dose (-180 min, -60 min and -30 min). Then at time point 0, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360.

Eligibility
Key inclusion criteria
ICU patients:
*Adults (greater than or equal to 18 years of age)
*Admitted to the Royal Adelaide Hospital Intensive Care Unit
*Mechanically ventilated
*Suitable for enteral feeding
*Arterial line insitu
*Consent obtained

Healthy volunteer arm:
*Adults (greater than or equal to 18 years of age)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
ICU patients:
*Recent upper abdominal surgery
*Vegan
*Lactose intolerance
*Any order to withhold active treatment
*Jehovah’s Witness
*For muscle biopsy: Bleeding diathesis (INR > 1.5; APTT > 50) including those receiving anticoagulants (other than low dose for DVT prophylaxis) and anti-platelet agents


Healthy volunteer arm:
*Significant illness
*Smokers (cigarettes/cigars/marijuana)
*Intake of >2 standard drinks on >5 days per week
*Intake of >4 cups of caffeinated drinks per day
*Intake of any illicit substance
*Vegan
*Lactose intolerance
*Use of prescribed or non-prescribed medications that may affect gastrointestinal function
*Significant gastrointestinal symptoms, disease or surgery (apart from uncomplicated appendectomy)
*For muscle biopsy: Bleeding diathesis (INR > 1.5; APTT > 50) including those receiving anticoagulants (other than low dose for DVT prophylaxis) and anti-platelet agents

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
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] 6983 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 14696 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 295057 0
Hospital
Name [1] 295057 0
Royal Adelaide Hospital Research Committee Project Grant
Address [1] 295057 0
Royal Adelaide Hospital, North Terrace, 5000, Adelaide, South Australia, Australia
Country [1] 295057 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Royal Adelaide Hospital, North Terrace, 5000, Adelaide, South Australia, Australia
Country
Australia
Secondary sponsor category [1] 293871 0
None
Name [1] 293871 0
Address [1] 293871 0
Country [1] 293871 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296403 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 296403 0
Royal Adelaide Hospital
Port Road
Adelaide, SA 5000
Ethics committee country [1] 296403 0
Australia
Date submitted for ethics approval [1] 296403 0
30/11/2016
Approval date [1] 296403 0
Ethics approval number [1] 296403 0
Ethics committee name [2] 303873 0
CAHLN HREC
Ethics committee address [2] 303873 0
Royal Adelaide Hospital
Port Road
Adelaide, SA 5000
Ethics committee country [2] 303873 0
Australia
Date submitted for ethics approval [2] 303873 0
05/12/2016
Approval date [2] 303873 0
02/03/2017
Ethics approval number [2] 303873 0
HREC/16/RAH/505

Summary
Brief summary
Single centre exploratory unblinded observational study. Using a unique method that has been developed to label intact proteins rather than amino acids by infusing cows with large quantities of D5-phenylalanine and then collecting their labelled milk. This labelled cow milk can then be administered to humans for research purposes and the metabolic fate of the protein determined. This technique allows the fate of intact protein to be followed from ingestion, through digestion and absorption to muscle deposition. The biological value of the protein can thus be determined i.e. the proportion that becomes incorporated into body tissues, particularly muscle. This is relevant in the critically ill as the protein content of enteral feed formulae is usually presented as a protein such as casein or whey protein. Reduced amino acid absorption has been reported in rats following haemorrhagic shock, in patients with pancreatitis, and in critically ill patients following trauma. However the mechanisms underlying protein malabsorption are not well understood. A more comprehensive understanding of protein absorption during critical illness, and the effect of feeding intolerance on protein uptake will allow the rational development of feeding strategies to improve nutritional outcomes in these patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 70778 0
Prof Marianne Chapman
Address 70778 0
Royal Adelaide Hospital, North Terrace, 5000, Adelaide, South Australia, Australia
Country 70778 0
Australia
Phone 70778 0
+61 8 8222 4624
Fax 70778 0
Email 70778 0
marianne.chapman@sa.gov.au
Contact person for public queries
Name 70779 0
Dr Lee-anne Chapple
Address 70779 0
Royal Adelaide Hospital, North Terrace, 5000, Adelaide, South Australia, Australia
Country 70779 0
Australia
Phone 70779 0
+61 8 8222 4624
Fax 70779 0
Email 70779 0
lee-anne.chapple@adelaide.edu.au
Contact person for scientific queries
Name 70780 0
Dr Lee-anne Chapple
Address 70780 0
Royal Adelaide Hospital, North Terrace, 5000, Adelaide, South Australia, Australia
Country 70780 0
Australia
Phone 70780 0
+61 8 8222 4624
Fax 70780 0
Email 70780 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
Not available
What supporting documents are/will be available?
No other documents available
Summary results
No Results