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Trial registered on ANZCTR


Registration number
ACTRN12617000384358
Ethics application status
Approved
Date submitted
2/03/2017
Date registered
15/03/2017
Date last updated
28/07/2024
Date data sharing statement initially provided
26/02/2020
Date results provided
5/07/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of standard versus energy dense feeds on gastric emptying and glucose metabolism in critically ill patients
Scientific title
The effect of standard versus energy dense feeds on gastric emptying and glucose metabolism in critically ill patients
Secondary ID [1] 290663 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical Illness 301192 0
Condition category
Condition code
Diet and Nutrition 300943 300943 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be studied on two consecutive days, in which they will receive either standard feed (1 kcal/ml) or energy dense feed (2 kcal/ml), in a randomised, double blind fashion. On each day, enteral feeding will be ceased four hours prior to the commencement of the study. Blood glucose levels will be managed according to the Royal Adelaide Hospital Intensive Care Unit protocol i.e. <10 mmol/l. However, due to patients not receiving feeds following the test meal, exogenous insulin infusions will be ceased prior to the commencement of the test meal. Computer randomisation will be performed by a nuclear medicine technician, who will measure out the study feed and add the radioactive marker. This nuclear medicine technician will not be involved in the conduct of the study or interpretation of the results and will instill the study feed to ensure allocation concealment is maintained.

At t = -5, an intragastric ‘meal’ will be infused over 5 minutes. The meal will contain 200 ml of ‘Standard’ feed (Nutrison 1kcal/ml, Nutricia Australia, containing carbohydrate 49%, fat 35%, and protein 16%, osmolality 305 mOsm/kg H2O) or 100 ml of ‘Energy dense’ feed (TwoCal 2kcal/ml, Abbott Nutrition, containing carbohydrate 43%, fat 40%, and protein 17%, osmolality 690 mOsm/kg H2O). The order in which standard or energy dense feeds are given will depend on randomisation.

The meal will also contain 3 g of 3-O-Methyl-D-gluco-pyranose (3-OMG) (Sigma-Aldrich) dissolved in 5 ml H2O and 20MBq 99mTc-calcium phytate colloid. Radioisotopic data will be acquired in dynamic mode every minute for the first 60 minutes and every 3 minutes thereafter for a total of 240 minutes using a gamma camera (DigiRad 2020tc, Gammasonics) with the patient lying in the semi-recumbent position. An arterial blood sample will be obtained every 15 minutes for the first hour and every 30 minutes thereafter for measurement of blood glucose concentration, plasma GLP-1, CCK, PYY and Glucagon, and serum Insulin, C-peptide and 3-OMG. Enteral nutrition will be commenced immediately on study completion (4 hours following meal administration).
Intervention code [1] 296542 0
Treatment: Other
Comparator / control treatment
Patients will act as their own control group, and we expect there will be no difference between the two arms. The standard feed (1 kcal/ml) will be considered as the standard treatment.
Control group
Active

Outcomes
Primary outcome [1] 300367 0
To compare rate of gastric emptying of a 1 and 2 kcal/ml isocaloric liquid nutrient in critically ill patients using scintigraphy.
Timepoint [1] 300367 0
The content of the total stomach at 5, 15, 30, 45, 60, 90, 120 (main), 150, 180, 210 and 240 minutes after the meal will be assessed to determine gastric emptying
Secondary outcome [1] 329803 0
To evaluate the effects of 1 and 2 kcal/ml feeds on glucose absorption using plasma concentrations of the glucose analogue 3-OMG. Three grams of 3-OMG will be mixed with the test meal and infused into the duodenum. The rate of glucose absorption is indicated by the area under the 3-OMG concentration curve, peak concentration and time to peak.
Timepoint [1] 329803 0
Blood samples will be collected at timed intervals (0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min) following test meal administration, and analysed for plasma 3-OMG concentration using High Performance Liquid Chromatography.
Secondary outcome [2] 332353 0
Plasma concentrations of GLP-1
Timepoint [2] 332353 0
Blood samples will be collected at timed intervals (0, 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min) following test meal administration.
Secondary outcome [3] 332356 0
Plasma concentrations of glucagon
Timepoint [3] 332356 0
Blood samples will be collected at timed intervals (0, 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min) following test meal administration.
Secondary outcome [4] 332357 0
Plasma concentrations of CCK
Timepoint [4] 332357 0
Blood samples will be collected at timed intervals (0, 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min) following test meal administration.
Secondary outcome [5] 332358 0
Plasma concentrations of PYY
Timepoint [5] 332358 0
Blood samples will be collected at timed intervals (0, 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min) following test meal administration.
Secondary outcome [6] 332359 0
Plasma concentrations of GIP
Timepoint [6] 332359 0
Blood samples will be collected at timed intervals (0, 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min) following test meal administration.
Secondary outcome [7] 332360 0
Plasma concentrations of C-Peptide secretion
Timepoint [7] 332360 0
Blood samples will be collected at timed intervals (0, 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min) following test meal administration.

Eligibility
Key inclusion criteria
Mechanically ventilated critically ill patients who are:
-Aged >18 years of age
-Receiving or suitable to receive enteral nutrition
-Anticipated to remain mechanically ventilated for a further 48 hours
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded if they meet one of the following:
-Pregnancy
-Receiving gastrokinetic drugs (including Erythromycin, Metoclopramide, Azithromycin, Domperidone, Prucalopride)
-Gastrointestinal surgery on this admission
-Previous upper gastrointestinal surgery (oesophageal, stomach or duodenal)
-Unable to obtain informed consent

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)
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 receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
This will be a randomised, double blind, cross over non-inferiority study performed on consecutive days in critically ill patients.
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary endpoint is gastric emptying response to energy dense feeds. This will be measured via scintigraphy, which remains the most accurate method to quantify gastric emptying in the critically ill. Scintigraphic data will be captured with the patient using a mobile gamma camera with 1-3 minute dynamic frame acquisition. A region of interest will be drawn around the total stomach, with gastric emptying curves generated over time and the intragastric retention at 15 minute intervals calculated. In addition, from these data, the kcal emptied into the duodenum can also be calculated. Data will analysed by the same individual blinded to the study conditions. Total areas under the curve from baseline to 240 minutes (AUC240) will be calculated for gastric emptying, calorie delivery and blood glucose using the trapezoidal rule. Data on gastric emptying from a previous scintigraphic study in the critically ill estimated the within subject variability of gastric retention to be 42%. Based on this, n=20 patients will achieve 80% power at 5% significance to determine non-inferiority of gastric retention with a non-inferiority margin of 24 percentage points. Non-inferiority will be indicated if the lower bound of the 95% confidence interval of the difference in gastric retention is greater than the non-inferiority margin. That is, gastric retention at T=120 minutes for the 2 kcal/ml feed will be no more than 24 percentage points less than for the 1 kcal/ml feed. The non-inferiority margin is based on both expert opinion and previous research.. Secondary outcomes will be analysed via paired t-tests. Approval to recruit up to twenty-five patients is requested to allow for drop-outs.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/04/2017
Actual
16/05/2017
Date of last participant enrolment
Anticipated
Actual
26/02/2019
Date of last data collection
Anticipated
Actual
28/02/2019
Sample size
Target
25
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 7592 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 15490 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 295797 0
Hospital
Name [1] 295797 0
Intensive Care Research, Royal Adelaide Hospital
Country [1] 295797 0
Australia
Primary sponsor type
Hospital
Name
Intensive Care Research Unit, Royal Adelaide Hospital
Address
Level 4G751,
Intensive Care Unit,
Royal Adelaide Hospital,
Port Road,
Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 294645 0
None
Name [1] 294645 0
None
Address [1] 294645 0
None
Country [1] 294645 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297092 0
CALHN Human Research Ethics Committee
Ethics committee address [1] 297092 0
Ethics committee country [1] 297092 0
Australia
Date submitted for ethics approval [1] 297092 0
12/12/2016
Approval date [1] 297092 0
01/03/2017
Ethics approval number [1] 297092 0
HREC/16/RAH/503

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

Contacts
Principal investigator
Name 70878 0
Ms Lee-anne Chapple
Address 70878 0
Level 4G751, Intensive Care Unit, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000.
Country 70878 0
Australia
Phone 70878 0
+61 8 7074 1763
Fax 70878 0
Email 70878 0
lee-anne.costello@adelaide.edu.au
Contact person for public queries
Name 70879 0
Lee-anne Chapple
Address 70879 0
Level 4G751, Intensive Care Unit, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000.
Country 70879 0
Australia
Phone 70879 0
+61 8 7074 1763
Fax 70879 0
Email 70879 0
lee-anne.costello@adelaide.edu.au
Contact person for scientific queries
Name 70880 0
Lee-anne Chapple
Address 70880 0
Level 4G751, Intensive Care Unit, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000.
Country 70880 0
Australia
Phone 70880 0
+61 8 7074 1763
Fax 70880 0
Email 70880 0
lee-anne.costello@adelaide.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.