ANZCTR - Registration

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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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Critical illness

Condition category

Condition code

Metabolic and Endocrine

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]

Treatment: Other

Comparator / control treatment

No control group.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

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]

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]

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]

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]

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]

Intestinal glucose absorption, assessed by the mean serum concentration of 3-O-methylglucose at the primary timepoint as measured by LCMS.

Timepoint [1]

Mean plasma concentration from four blood samples drawn at 150, 160, 170 and 180 minutes after initial substrate administration (time 0).

Secondary outcome [2]

Plasma free amino acid concentrations.

Timepoint [2]

180 minutes.

Secondary outcome [3]

Plasma urea concentration,

Timepoint [3]

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?

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

Accrual to date

Final

Recruitment outside Australia

Country [1]

Sweden

State/province [1]

Stockholm county

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and Karolinska Institutet

Address [1]

Stockholm County Council
Stockholms lans landsting
Box 22550
104 22 Stockholm

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Regionala etikprovningsnamnden i Stockholm

Ethics committee address [1]

Box 289 (Nobels vag 12 A)
171 77 Stockholm

Ethics committee country [1]

Sweden

Date submitted for ethics approval [1]

22/12/2014

Approval date [1]

11/02/2015

Ethics approval number [1]

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

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

Phone

+46-8-58580553

Fax

olav.rooyackers@ki.se

Contact person for public queries

Name

Olav Rooyackers

Address

Karolinska Institutet Inst. for klinisk vetenskap, intervention och teknik. Enheten for anestesi. Karolinska Universitetssjukhuset, Huddinge, K32 141 86 Stockholm

Country

Sweden

Phone

+46-8-58580553

Fax

olav.rooyackers@ki.se

Contact person for scientific queries

Name

Olav Rooyackers

Address

Karolinska Institutet Inst. for klinisk vetenskap, intervention och teknik. Enheten for anestesi. Karolinska Universitetssjukhuset, Huddinge, K32 141 86 Stockholm

Country

Sweden

Phone

+46-8-58580553

Fax

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.	Type	Email
5147	Ethical approval	martin.sundstrom@gmail.com
5366	Informed consent form	martin.sundstrom@gmail.con
5367	Study protocol	martin.sundstrom@gmail.con

Results publications and other study-related documents

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Documents added automatically

No additional documents have been identified.

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