Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001094662
Ethics application status
Approved
Date submitted
24/09/2014
Date registered
15/10/2014
Date last updated
15/10/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
Glutamine kinetics in intensive care unit patients – relation between plasma concentration and endogenous production
Scientific title
Observational study of the relation between plasma glutamine concentration and endogenous production in ICU patients.
Secondary ID [1] 285386 0
None
Universal Trial Number (UTN)
U1111-1162-1906
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Low plasma glutamine and critical illness 293126 0
High plasma glutamine and critical illness 293127 0
Liver failure 293128 0
Condition category
Condition code
Metabolic and Endocrine 293395 293395 0 0
Other metabolic disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
To measure endogenous glutamine production in ICU patients by a previously verified bolus injection method (Mori et al. PLoS One 2014 8;9(5) e96601). Subjects will receive a bolus injection of both glutamine and phenylalanine labeled with a stable isotope (1-13C-glutamine 3 mg/kg; ring2H5-phenylalanine 0.3 mg/kg). Bolus will be given over 20 seconds followed by 60 blood samples over 90 min to get a decay curve. Initially 1 sample every 30 sec, then every 60 sec and finally every 3 min. Each blood sample is 0,5 mL. During the measurement nutrition should be constant; to achieve this nutrition will not be altered two hours prior to the measurement or during the 90 minutes that blood samples are collected.
Four different groups will be studied:
1. 20 patients with low plasma glutamine (<420 umol/L) at admission to the ICU.
2. 20 patients with high plasma glutamine (>900 umol/L) at admission to the ICU.
3. 20 patients staying >5 days in the ICU.
4. 20 patients with high plasma glutamine (>900 umol/L) at admission to the ICU and liver failure.
Group 1 and 2 will be measured once in the first week of ICU stay. Group 3 will be measured several times with 3-5 days intervals. Group 4 will be measured several times with 2-3 days intervals. A subject may be included in more than one group.
Intervention code [1] 290305 0
Not applicable
Comparator / control treatment
No control treatment.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 293226 0
Glutamine endogenous production or synthesis is assessed with injection of a small amount of labeled glutamine (labeled with a stable isotope; 13C). By taking frequent plasma samples and analyzing these for the decay of the labeled glutamine the endogenous production of glutamine can be analyzed by dividing the bolus dose of labeled glutamine by the area under the curve for the decay in plasma.
Timepoint [1] 293226 0
First week of ICU stay. Measured over 90 minutes on one occasion only in groups 1 and 2, on 1-2 occasions in Group 3, and on 2-3 occasions in Group 4.
Secondary outcome [1] 310628 0
Change in glutamine synthesis during ICU stay. Endogenous production is assessed with injection of a small amount of labeled glutamine (labeled with a stable isotope; 13C). By taking frequent plasma samples and analyzing these for the decay of the labeled glutamine the endogenous production of glutamine can be analyzed by dividing the bolus dose of labeled glutamine by the area under the curve for the decay in plasma.
Several measurements are made for groups 3+4. These will be compared to see if there is a change over time.
Timepoint [1] 310628 0
2-5 days after previous measurement as long as in the ICU (maximum 3 measurements/2 week period).
Secondary outcome [2] 310646 0
Glutamine de novo production and production from protein breakdown.
Glutamine endogenous production is coming from 2 sources; de novo synthesis and from breakdown of protein. To distinguish between the two we will assess whole body protein breakdown using a labeled phenylalanine (2H5-phenylalanine) in the same way as for the labeled glutamine (phenylalanine endogenous production is calculated from bolus divided by area under the curve for plasma 2H25-phenyalanine). Since phenylalanine is an essential amino acid its endogenous production can only come from protein breakdown. By assuming a ratio of phenylalnine to glutamine content in whole body protein the amount of glutamine coming from protein breakdown can be estimated. By subtracting the glutamine coming from protein breakdown from the total glutamine endogenous production, de novo production of glutamine is calculated (as in Mori et al Crit Care 2014 14;18(2)R72).
Timepoint [2] 310646 0
First week of ICU stay and 2-5 days after previous measurement as long as in the ICU (maximum 3 measurements/2 week period).

Eligibility
Key inclusion criteria
Group 1: Plasma glutamine <420 umol/l at admission to the ICU.
Group 2: Plasma glutamine >900 umol/l at admission to the ICU.
Group 3: Expected length of stay in ICU >5 days.
Group 4: Plasma glutamine >900umol/l at admissio to the ICu and liver failure.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Absence of informed consent.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
To detect a 25% difference in endogenous glutamine production rates between group 1 and 2 (primary outcome) with a 80% power, 19 patients are needed in each group based on variation in previous study in similar patients (Mori et al Crit Care 2014 14;18(2)R72).

Since repeated measures of glutamine endogenous production are not performed before we do not know the variation and will not be able to calculate power on the groups with repeated measures. The comparison between the low and the high glutamine production is the key question and therefore the study is powered to answer this question. The other groups are of the same size as an pragmatic approach and will give us data to in future studies calculate power also for repeated measurements. However since the repeated measurements will allow us to use paired analyses, the obtained higher power will most likely make this part of the study over powered rather than under powered.

Primary analysis: For comparison between group 1 and 2 using t-test or Mann-Whitney.
For repeated measurements ANOVA.

Secondary analysis: Regression analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
25/09/2014
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment outside Australia
Country [1] 6374 0
Sweden
State/province [1] 6374 0

Funding & Sponsors
Funding source category [1] 290002 0
Government body
Name [1] 290002 0
Supported by grants provided by the Stockholm County Council (ALF project)
Country [1] 290002 0
Sweden
Primary sponsor type
Individual
Name
Jan Wernerman
Address
Karolinska Institutet, Department of Clinical Science, Intervention and Technology (CLINTEC)
and
Dept. Anesthesiology and Intensive Care, B31
Karolinska University Hospital Huddinge
SE-141 86 Stockholm, Sweden
Country
Sweden
Secondary sponsor category [1] 288685 0
None
Name [1] 288685 0
Address [1] 288685 0
Country [1] 288685 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291706 0
Regional Ethical Board in Stockholm
Ethics committee address [1] 291706 0
Ethics committee country [1] 291706 0
Sweden
Date submitted for ethics approval [1] 291706 0
Approval date [1] 291706 0
19/02/2014
Ethics approval number [1] 291706 0
2014/68-31/2

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

Contacts
Principal investigator
Name 51634 0
Prof Jan Wernerman
Address 51634 0
Karolinska Institutet, Department of Clinical Science, Intervention and Technology (CLINTEC) and Dept. Anesthesiology and Intensive Care, B31 Karolinska University Hospital Huddinge SE-141 86 Stockholm, Sweden
Country 51634 0
Sweden
Phone 51634 0
+46 8 58 58 00 00
Fax 51634 0
Email 51634 0
[email protected]
Contact person for public queries
Name 51635 0
Marie Smedberg
Address 51635 0
Dept. Anesthesiology and Intensive Care, B31 Karolinska University Hospital Huddinge SE-141 86 Stockholm, Sweden
Country 51635 0
Sweden
Phone 51635 0
+46 8 58 58 00 00
Fax 51635 0
Email 51635 0
[email protected]
Contact person for scientific queries
Name 51636 0
Marie Smedberg
Address 51636 0
Dept. Anesthesiology and Intensive Care, B31 Karolinska University Hospital Huddinge SE-141 86 Stockholm, Sweden
Country 51636 0
Sweden
Phone 51636 0
+46 8 58 58 00 00
Fax 51636 0
Email 51636 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
EmbaseEndogenous production of glutamine and plasma glutamine concentration in critically ill patients.2020https://dx.doi.org/10.1016/j.clnesp.2020.09.015
N.B. These documents automatically identified may not have been verified by the study sponsor.