Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000544279
Ethics application status
Approved
Date submitted
8/11/2017
Date registered
11/04/2018
Date last updated
11/04/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effect of early feeding on the regulation of autophagy in critically ill children
Scientific title
Effect of early feeding on the regulation of autophagy in critically ill children
Secondary ID [1] 293309 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical illness 305392 0
Pediatric ICU nutrition 306455 0
Condition category
Condition code
Diet and Nutrition 304678 304678 0 0
Other diet and nutrition disorders
Metabolic and Endocrine 306354 306354 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Supplementary parenteral nutrition when enteral nutrition is not up to target on day 5

Nutritional target is defined as: energy target according to Schofield equation.

For enteral nutrition different formulas are used depending on age and are given continuously either via nasogastric or post-pyloric tube (decided by the treating clinician).

Supplementary parenteral nutrition is given as different commercial formulas (Baxter): Numeta G16E (<10 kg body weight); Numeta G19E (10-15 kg body weight) and Olimel N5 (>15kg body weight). The amount given is: 67% of total nutritional target on day 5-6; 85% of total nutritional target on day 7-8 and 100% of total nutritional target from day 9 as long as in the ICU.

The intervention is ordinated by treating clinician and administered by treating nurse.
Intervention code [1] 299569 0
Treatment: Other
Comparator / control treatment
Supplementary parenteral nutrition when enteral nutrition is not up to target on day 2

Nutritional target is defined as: energy target according to Schofield equation.

For enteral nutrition different formulas are used depending on age and are given continuously either via nasogastric or post-pyloric tube (decided by the treating clinician).

Supplementary parenteral nutrition is given as different commercial formulas (Baxter): Numeta G16E (<10 kg body weight); Numeta G19E (10-15 kg body weight) and Olimel N5 (>15kg body weight). The amount given is: 67% of total nutritional target on day 2-5; ; 85% of total nutritional target on day 6-8 and 100% of total nutritional target from day 9 as long as in the ICU.
Control group
Active

Outcomes
Primary outcome [1] 303895 0
Measurement of autophagy flux using an in vitro assay.

Primary human myotubes will be incubated with serum from patients and autophagy flux will be measured using in cell expression of P62 using antibodies with and without chemical blocking of the autophagy flux.
Timepoint [1] 303895 0
Days 1, 3 (primary timepoint) and 6
Secondary outcome [1] 340374 0
Organ failure measured as PELOD 2 score
Timepoint [1] 340374 0
Days 1, 3 and 6
Secondary outcome [2] 340375 0
Amino acid concentrations in serum analyzed using a standard HPLC technique.
Timepoint [2] 340375 0
Days 1, 3 and 6
Secondary outcome [3] 340376 0
Amount of protein in the nutrition calculated from medical records.
Timepoint [3] 340376 0
Days 1, 3 and 6
Secondary outcome [4] 340377 0
Amount of fat in the nutrition calculated from medical records.
Timepoint [4] 340377 0
Days 1, 3 and 6
Secondary outcome [5] 340378 0
Carbohydrates in the nutrition calculated from medical records.
Timepoint [5] 340378 0
Days 1, 3 and 6
Secondary outcome [6] 340379 0
Energy intake calculated from medical records.
Timepoint [6] 340379 0
Days 1, 3, and 6
Secondary outcome [7] 340401 0
Concentrations of energy substrates (glucose, fatty acids) in serum.using standard enzymatic and photospectrometric analyses.
Timepoint [7] 340401 0
Days 1, 3 and 6

Eligibility
Key inclusion criteria
Treated at pediatric ICU; ongoing mechanical ventilation; Two or more failing organs; expected ICU stay of more than 2 days
Minimum age
No limit
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
No informed consent

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Under the first period control patients will be studied using the present routine of starting supplementary parenteral nutrition on day 2. When all patients are included (n=20) the routine will be changed to the new routine with supplementary parenteral nutrition on day 5. After 2 weeks of implementing the new routine, the treatment patients will be included (n=20).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Other
Other design features
Groups will be studied sequentially.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
From our preliminary data on adult ICU patients, we calculated that we can detect a 30% difference in autophagy flux between the groups with a 80% power using 20 patients in each group.

Primary outcome will be analyzed using ANOVA for repeated measures. If data is not normally distributed, logarithmic data will be used. Secondary outcomes will be analyzed using Pearson regression analyses.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
5/03/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
3
Final
Recruitment outside Australia
Country [1] 9339 0
Sweden
State/province [1] 9339 0

Funding & Sponsors
Funding source category [1] 297934 0
Charities/Societies/Foundations
Name [1] 297934 0
Swedish Research Council
Country [1] 297934 0
Sweden
Primary sponsor type
Individual
Name
Urban Fläring
Address
Pediatric ICU
Astrid Lindgren Children's Hospital
Eugeniavägen 23,
171 64 Solna
Sweden
Country
Sweden
Secondary sponsor category [1] 296997 0
Individual
Name [1] 296997 0
Olav Rooyackers
Address [1] 296997 0
Perioperative Medicine and Intensive Care
Karolinska University Hospital
Logopedvägen 3
14157 Huddinge
Sweden
Country [1] 296997 0
Sweden
Other collaborator category [1] 279793 0
Individual
Name [1] 279793 0
Nicolas Tardif
Address [1] 279793 0
CLINTEC
Karolinska Institutet
Stockholm
Country [1] 279793 0
Sweden

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298980 0
Regional Ethical Committee Stockholm
Ethics committee address [1] 298980 0
Karolinska Institutet i Solna
Widerströmska huset
Tomtebodavägen 18A, plan 3 (använd hiss 1 till vänster när man kommer in)
171 65 Solna
Ethics committee country [1] 298980 0
Sweden
Date submitted for ethics approval [1] 298980 0
Approval date [1] 298980 0
20/10/2017
Ethics approval number [1] 298980 0
Dnr: 2017/1639-31

Summary
Brief summary
A recent large randomized trial has shown that a later start with supplementary parenteral nutrition when enteral nutrition is not working in full reduces ICU patient’s disease and length of ICU treatment. This has been shown in both adult and pediatric ICU patients. It has been hypothesized from these trails, that the early supplementary parenteral nutrition inhibits autophagy in cells. Autophagy is the cellular process that degrades larger proteins and organelles especially when they are damaged. The hypothesized inhibition of the autophagy process will then lead to the buildup of more damaged proteins and prolong/worsen the cellular and thereby organ function. At the pediatric ICU management, has decided to change the routine from early supplementary parenteral nutrition (day 2) to a later day (day 5) based on the clinical outcome trials. We will use this change to investigate the effect of initiating early feeding and later feeding on the potential of the patient’s serum to inhibit the autophagy flux in an in vitro model. There are no methods available to measure the autophagy flux in vivo in humans. In addition, we will relate the changes in autophagy flux to nutrients concentrations and clinical parameters.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78878 0
Dr Urban Fläring
Address 78878 0
Pediatric ICU
Astrid Lindgren Children's Hospital
Eugeniavägen 23,
171 64 Solna
Sweden
Country 78878 0
Sweden
Phone 78878 0
+46 8 51770394
Fax 78878 0
Email 78878 0
urban.flaring@sll.se
Contact person for public queries
Name 78879 0
Prof Olav Rooyackers
Address 78879 0
Perioperative Medicine and Intensive Care
Karolinska University Hospital
Logopedvägen 3
14157 Huddinge
Sweden
Country 78879 0
Sweden
Phone 78879 0
+46 8 58586182
Fax 78879 0
Email 78879 0
olav.rooyackers@ki.se
Contact person for scientific queries
Name 78880 0
Prof Olav Rooyackers
Address 78880 0
Perioperative Medicine and Intensive Care
Karolinska University Hospital
Logopedvägen 3
14157 Huddinge
Sweden
Country 78880 0
Sweden
Phone 78880 0
+46 8 58586182
Fax 78880 0
Email 78880 0
olav.rooyackers@ki.se

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Results publications and other study-related documents

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