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Trial registered on ANZCTR


Registration number
ACTRN12617001376336
Ethics application status
Approved
Date submitted
27/04/2017
Date registered
28/09/2017
Date last updated
21/10/2019
Date data sharing statement initially provided
21/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
An investigation of the handling of glucose, fat and protein in critically ill patients.
Scientific title
Whole-body substrate turnover in critically ill patients: a pilot study of a multi-substrate stable isotope tracer method.
Secondary ID [1] 291515 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical illness 302603 0
Condition category
Condition code
Metabolic and Endocrine 302125 302125 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
At time 0 an enteral infusion of [U-13C6]-glucose (at a rate calculated to obtain a 30% enrichment of enteral glucose content), [1-13C]-phenylalanine (at a rate calculated to obtain a 30% enrichment of enteral phenylalanine content) and 3-O-methylglucose (infusion 20 mg/kg/h) is added to the ongoing enteral nutrition to measure absorption and enteral utilization of substrates. Simultaneously, a measurement of energy expenditure by indirect calorimetry is started to be continued during the entire protocol. At t 120 minutes, primed intravenous infusions of [ring-2H5]-phenylalanine (bolus 0.5 mg/kg, infusion 0.5 mg/kg/h), [ring-2H4]-Tyrosine (bolus 0.15 mg/kg), [2H2]-Tyrosine (bolus 0.3 mg/kg, infusion 0.3 mg/kg/h), 2H2-glucose (bolus 3 mg/kg, infusion 2.4 mg/kg/h) and 2H2-glycerol (bolus 0.15 mg/kg, infusion 0.33 mg/kg/h) are initiated to measure endogenous substrate turnover. After 150 minutes, plasma samples will be draw from the arterial line four times at 10 minute intervals to determine steady-state concentration of all the tracers. Whole-body protein turnover from phenylalanine kinetics, glucose turnover, intestinal glucose absorption, and lipolysis from glycerol rate of appearance are calculated from these values. The final sample is also analyzed for glucose, triglyceride, free fatty acids, glycerol, amino acid and urea concentrations.

All aspects of patient care are governed by the attending intensivist, but the rates of enteral and parenteral nutrition are to remain constant 3 hours prior to and during the study period.
Intervention code [1] 297589 0
Treatment: Other
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 301559 0
Whole-body phenylalanine kinetics (breakdown, synthesis, oxidation) calculated from the endogenous rate of appearance at isotopic enrichment plateau. Phenylalanine oxidation is estimated by the hydroxylation rate of phenylalanine to tyrosine.

Rate of appearance is calculated from the tracer enrichment in plasma and the tracer infusion rate. Enrichment is quantified by the mean values from four blood samples at the primary timepoint. These are centrifugated to plasma and analyzed for tracer/tracee concentrations by LCMS.
Timepoint [1] 301559 0
Tracer plasma enrichment is quantified by the mean plasma concentration from four blood samples drawn at 150, 160, 170 and 180 minutes after initial substrate administration (t=0).
Primary outcome [2] 302171 0
Whole body glucose kinetics (synthesis, uptake) calculated from endogenous rate of appearance at isotopic enrichment plateau.

Rate of appearance is calculated from the tracer enrichment in plasma and the tracer infusion rate. Enrichment is quantified by the mean values from four blood samples at the primary timepoint. These are centrifugated to plasma and analyzed for tracer/tracee concentrations by LCMS.
Timepoint [2] 302171 0
Tracer plasma enrichment is quantified by the mean plasma concentration from four blood samples drawn at 150, 160, 170 and 180 minutes after initial substrate administration (t=0).
Primary outcome [3] 302172 0
Whole body glycerol kinetics (=rate of lipolysis) calculated from endogenous rate of appearance at isotopic enrichment plateau.

Rate of appearance is calculated from the tracer enrichment in plasma and the tracer infusion rate. Enrichment is quantified by the mean values from four blood samples at the primary timepoint. These are centrifugated to plasma and analyzed for tracer/tracee concentrations by LCMS.
Timepoint [3] 302172 0
Tracer plasma enrichment is quantified by the mean plasma concentration from four blood samples drawn at 150, 160, 170 and 180 minutes after initial substrate administration (t=0).
Secondary outcome [1] 333023 0
Intestinal glucose absorption, assessed by the mean serum concentration of 3-O-methylglucose at the primary timepoint as measured by LCMS.
Timepoint [1] 333023 0
Mean plasma concentration from four blood samples drawn at 150, 160, 170 and 180 minutes after initial substrate administration (time 0).
Secondary outcome [2] 334244 0
Plasma free amino acid concentrations.
Timepoint [2] 334244 0
180 minutes.
Secondary outcome [3] 335053 0
Plasma urea concentration,
Timepoint [3] 335053 0
180 minutes.

Eligibility
Key inclusion criteria
All patients in the ICU of Karolinska University Hospital Huddinge >/=18 years of age and receiving invasive mechanical ventilation will be screened for participation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria are i. factors present that limit the precision of indirect calorimetry (FiO2 >0.6, significant gas leaks) ii. no arterial line available for blood samples and iii. lack of informed consent by the patient or family member.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
As this is a pilot feasibility study there is no power calculation for sample size. An arbitrary recruitment target of 18 patients has been chosen to allow for a certain variability in energy expenditure and exploratory analysis for future studies. Descriptive statistics will be performed.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/02/2020
Actual
Date of last participant enrolment
Anticipated
28/09/2020
Actual
Date of last data collection
Anticipated
28/09/2020
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment outside Australia
Country [1] 8761 0
Sweden
State/province [1] 8761 0
Stockholm county

Funding & Sponsors
Funding source category [1] 296005 0
Government body
Name [1] 296005 0
Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and Karolinska Institutet
Country [1] 296005 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] 294892 0
None
Name [1] 294892 0
Address [1] 294892 0
Country [1] 294892 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297267 0
Regionala etikprovningsnamnden i Stockholm
Ethics committee address [1] 297267 0
Box 289 (Nobels vag 12 A)
171 77 Stockholm
Ethics committee country [1] 297267 0
Sweden
Date submitted for ethics approval [1] 297267 0
22/12/2014
Approval date [1] 297267 0
11/02/2015
Ethics approval number [1] 297267 0
2015/95-31/2

Summary
Brief summary
Nutrition aimed at optimizing the provision of energy and protein during critical illness has been proposed as a potential therapy to improve both long- and short-term outcomes. So far, existing evidence is inconclusive. As ICU patients represent a very heterogenous population, in varying temporal phases of disease and recovery, it can be expected that a “one size fits all” approach will fail to improve outcomes. It has been hypothesized that in certain patients nutrition will not be able to suppress the endogenous energy and amino acid supply and basically the patent is overfed when eucaloric nutrition is supplied.

Given the lack of improvements in patient-centered outcomes that have resulted from trials of ICU nutrition, a better physiological understanding of macronutrient turnover is an essential step towards designing novel therapeutic approaches.

We plan to investigate whole-body protein, glucose and lipid turnover in ICU patients in relation to metabolic rate. This initial study is designed as a feasibility and pilot trial of a multi-substrate stable isotope tracer method for critically ill patients fed by the enteral route.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73518 0
Prof Olav Rooyackers
Address 73518 0
Karolinska Institutet Inst. for klinisk vetenskap, intervention och teknik. Enheten for anestesi. Karolinska Universitetssjukhuset, Huddinge, K32 141 86 Stockholm
Country 73518 0
Sweden
Phone 73518 0
+46-8-58580553
Fax 73518 0
Email 73518 0
olav.rooyackers@ki.se
Contact person for public queries
Name 73519 0
Prof Olav Rooyackers
Address 73519 0
Karolinska Institutet Inst. for klinisk vetenskap, intervention och teknik. Enheten for anestesi. Karolinska Universitetssjukhuset, Huddinge, K32 141 86 Stockholm
Country 73519 0
Sweden
Phone 73519 0
+46-8-58580553
Fax 73519 0
Email 73519 0
olav.rooyackers@ki.se
Contact person for scientific queries
Name 73520 0
Prof Olav Rooyackers
Address 73520 0
Karolinska Institutet Inst. for klinisk vetenskap, intervention och teknik. Enheten for anestesi. Karolinska Universitetssjukhuset, Huddinge, K32 141 86 Stockholm
Country 73520 0
Sweden
Phone 73520 0
+46-8-58580553
Fax 73520 0
Email 73520 0
olav.rooyackers@ki.se

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All de-identified data collected will be available on request.
When will data be available (start and end dates)?
From the date when data collection is finished (anticipated 28-09-2020) and onwards.
Available to whom?
The data will be available to researchers in the field on reasonable request to the Principal Investigator
Available for what types of analyses?
Not specified.
How or where can data be obtained?
Data will be made available on reasonable request by e-mail to the Principal Investigator (olav.rooyackers@sll.se).


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
5147Ethical approval  martin.sundstrom@gmail.com
5366Informed consent form  martin.sundstrom@gmail.con
5367Study protocol  martin.sundstrom@gmail.con



Results publications and other study-related documents

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

Documents added automatically
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