Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000476639
Ethics application status
Approved
Date submitted
17/04/2014
Date registered
8/05/2014
Date last updated
10/01/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of normocaloric vs. hypocaloric enteral nutrition on whole-body protein turnover in critically ill patients
Scientific title
Effects of normocaloric vs. hypocaloric enteral nutrition on whole-body protein turnover in critically ill patients
Secondary ID [1] 284290 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical illness 291435 0
Condition category
Condition code
Diet and Nutrition 291808 291808 0 0
Other diet and nutrition disorders
Metabolic and Endocrine 291809 291809 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Critically ill patients from a medical/surgical adult ICU who are on stable, normocaloric, enteral nutrition via nasogastric tube/gastrostomy/jejunostomy are studied twice on consecutive days. Indirect calorimetry is performed to determine energy expenditure. Enteral nutrition is given at 100% of energy expenditure (normocaloric) for 24 hrs on one day, and at 50% of energy expenditure (hypocaloric) for 24 hrs on the other, in randomised order.

Measurements of whole-body protein kinetics are made during the last 2 hrs of each 24 hr study period. Intravenous infusions of stable isotope labeled phenylalanine and tyrosine are administered to measure whole-body protein turnover. A different stable isotope labeled phenylalanine tracer is administered enterally during the last 5 hrs of each 24 hr study period to enable calculation of dietary contribution to whole-body protein turnover. Parameters of steady-state whole body protein turnover are calculated from arterial plasma enrichments of isotope labeled phenylalanine and tyrosine tracers.
Intervention code [1] 289013 0
Treatment: Other
Comparator / control treatment
Patients are studied twice on consecutive days and serve as their own controls. Normocaloric nutrition is considered the control and hypocolaric nutrition the intervention treatment.
Control group
Active

Outcomes
Primary outcome [1] 291872 0
Whole body net protein balance

Whole-body protein breakdown and synthesis is calculated from arterial plasma enrichments of isotope labeled phenylalanine and tyrosine tracers. The arithmetic difference of breakdown and synthesis is the net protein balance which is the main outcome. Intermediary calculations are also reported for clarity.
Timepoint [1] 291872 0
Parameters of whole body protein turnover are measured 22 hrs post initiation of normocaloric enteral nutrition and 22 hrs post initiation of hypocaloric enteral nutrition
Secondary outcome [1] 307707 0
Splanchnic extraction fraction of dietary phenylalanine is calculated from arterial plasma enrichments of isotope labeled phenylalanine and tyrosine tracers.
Timepoint [1] 307707 0
Splanchnic extraction fraction of dietary phenylalanine is measured 22 hrs post initiation of normocaloric enteral nutrition and 22 hrs post initiation of hypocaloric enteral nutrition
Secondary outcome [2] 307708 0
Plasma amino acid profile
Timepoint [2] 307708 0
Plasma amino acid profile is measured before intervention, 22 hrs post initiation of normocaloric enteral nutrition, and 22 hrs post initiation of hypocaloric enteral nutrition

Eligibility
Key inclusion criteria
Critically ill patients on stable, normocaloric, enteral nutrition nutrition via nasogastric feeding tube/gastrostomy/jejunostomy
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Blood transfusion during study period, intolerance of enteral nutrition at time of recruitment

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)
Patients are recruited from ICU clientele as available. Randomisation to order of treatment (first normocaloric, then hypocaloric vs. first hypocaloric, then normocaloric) is done by sealed opaque envelope drawing in blocks.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
A crossover design is used because the outcome measures are presumably subject to temporal variation, due to confounding factors such as the natural course of disease, complications, and therapeutic interventions.

Phase
Not Applicable
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
A sample size calculation was made using data from an earlier study from our group (Berg A et al. (2013), Crit Care 17(4): R158), using results for the endogenous rate of appearance of phenylalanine (endoRaPhe) which is the measurement on which further calculations are based. Assuming alpha=0.05 and beta=0.2, n=10 patients would be required to detect a 20% difference in endoRaPhe. N=12 patients will be studied to account for protocol violations that are unavoidable in the ICU setting.

With the interval of 24 hrs between measurements, a sufficient equilibration of protein metabolism in response to the altered substrate supply can be assumed, so that carry-over effects can be neglected. Therefore, results for each of the respective time points "normocaloric" and "hypocaloric" are pooled, irrespective of the group assignment. The pooled values are considered to constitute the outcome measure.

Statistical tests are made for the comparison between the two time points, appropriately by paired samples t-test (replaced by Wilcoxon signed rank test if sample distributions fail normality tests).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/12/2016
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2017
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment outside Australia
Country [1] 5972 0
Sweden
State/province [1] 5972 0

Funding & Sponsors
Funding source category [1] 289051 0
Government body
Name [1] 289051 0
Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and Karolinska Institutet
Country [1] 289051 0
Sweden
Primary sponsor type
Individual
Name
Prof Olav Rooyackers
Address
Karolinska Institutet
Inst. for klinisk vetenskap, intervention och teknik
Enheten for anestesi
Karolinska Universitetssjukhuset, Huddinge, K32
141 86 Stockholm
Country
Sweden
Secondary sponsor category [1] 287719 0
None
Name [1] 287719 0
Address [1] 287719 0
Country [1] 287719 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290749 0
Regionala etikprovningsnamnden i Stockholm
Ethics committee address [1] 290749 0
Ethics committee country [1] 290749 0
Sweden
Date submitted for ethics approval [1] 290749 0
30/04/2014
Approval date [1] 290749 0
17/02/2016
Ethics approval number [1] 290749 0
2016/76-31/4

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 47058 0
Prof Olav Rooyackers
Address 47058 0
Karolinska Institutet Inst. for klinisk vetenskap, intervention och teknik Enheten for anestesi Karolinska Universitetssjukhuset, Huddinge, K32 141 86 Stockholm
Country 47058 0
Sweden
Phone 47058 0
+46-8-58580553
Fax 47058 0
Email 47058 0
[email protected]
Contact person for public queries
Name 47059 0
Olav Rooyackers
Address 47059 0
Karolinska Institutet Inst. for klinisk vetenskap, intervention och teknik Enheten for anestesi Karolinska Universitetssjukhuset, Huddinge, K32 141 86 Stockholm
Country 47059 0
Sweden
Phone 47059 0
+46-8-58580553
Fax 47059 0
Email 47059 0
[email protected]
Contact person for scientific queries
Name 47060 0
Olav Rooyackers
Address 47060 0
Karolinska Institutet Inst. for klinisk vetenskap, intervention och teknik Enheten for anestesi Karolinska Universitetssjukhuset, Huddinge, K32 141 86 Stockholm
Country 47060 0
Sweden
Phone 47060 0
+46-8-58580553
Fax 47060 0
Email 47060 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseWhole-body protein kinetics in critically ill patients during 50 or 100% energy provision by enteral nutrition: A randomized cross-over study.2020https://dx.doi.org/10.1371/journal.pone.0240045
N.B. These documents automatically identified may not have been verified by the study sponsor.