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Trial registered on ANZCTR


Registration number
ACTRN12616000222448
Ethics application status
Approved
Date submitted
16/02/2016
Date registered
18/02/2016
Date last updated
24/02/2020
Date data sharing statement initially provided
24/02/2020
Date results information initially provided
24/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
What is the optimal dose of insulin for the protein content of a meal in individuals with type 1 diabetes mellitus using intensive insulin therapy
Scientific title
What is the optimal dose of insulin for the protein content of a meal in individuals with type 1 diabetes mellitus using intensive insulin therapy
Secondary ID [1] 288550 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes Mellitus 297658 0
Condition category
Condition code
Metabolic and Endocrine 297845 297845 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The aim of this study is to determine a safe and effective insulin dosing schedule to account for the protein content of a meal in order to improve postprandial glycaemia without increasing the risk of hypoglycaemia (low blood glucose levels [BGL's]) in individuals with T1DM.

A continuous glucose monitor (CGM) will be inserted on the day prior to the study to provide continuous
measurement of BGL's. For 5 consecutive days participants will be provided with a test breakfast drink containing 50g protein, 30g protein and non-fat. Insulin doses will be calculated using the participants usual insulin to carbohydrate ratio (ICR) with additional amounts of insulin
added in increasing increments of 15% These additional doses will be administered over 5 days in randomised order. The additional insulin amounts will be:
a) 0%
b) 15%
c) 30%
d) 45%
The insulin bolus will be programmed into the participants own insulin pump to commence delivery 15 minutes prior to consumption of the test meal, as per usual management. The insulin will be delivered using a dual wave or combination type bolus feature of the pump. The insulin will be delivered over 3 hours and the dose will be split 65/35% (65% given up front with the remaining dose given over 3 hours).
The participant will be given clear instructions of how to do this (most people using insulin pump therapy would be familiar with using wave bolus options) and the amount of insulin will be calculated by a member of the research team.
Participants will be contacted daily by a member of the research team to ensure adherence to the protocol. The participants insulin pump can be uploaded to a secure database each day for research staff to check the insulin doses and delivery.
Intervention code [1] 293929 0
Treatment: Other
Comparator / control treatment
Control treatment is giving the normal insulin dose.
This study will be a RCT and all participants will be their own control.
Control group
Dose comparison

Outcomes
Primary outcome [1] 297368 0
The primary outcome variable of this study is postprandial normoglycaemia (defined as the percent of time BGL’s remain within the target of 4-10 mmol/l in the 4 hour postprandial period) following the different doses of additional insulin for the protein content of the test meal. This will be assessed by 24 hour continuous glucose monitoring (CGM) for the duration of the study.
Timepoint [1] 297368 0
CGM for 4 hours postprandially.
Secondary outcome [1] 320831 0
Number of hypoglycaemic events in the 4 hour postprandial period (defined as BGL’s <3.5 mmol/l) assessed by CGM
Timepoint [1] 320831 0
Measured for 4 hours postprandially by CGM
Secondary outcome [2] 320832 0
Postprandial hyperglycaemia (defined as BGL’s >10.1 mmol/l) in the 4 hour postprandial period measured by CGM
Timepoint [2] 320832 0
Measured by CGM for 4 Hours postprandially
Secondary outcome [3] 320833 0
Glucose excursions at 30 minute intervals for the 4 hour postprandial period by CGM
Timepoint [3] 320833 0
Assessed every 30 minutes from completion of meal for 4 hours by CGM
Secondary outcome [4] 320834 0
Peak glucose level during the 6 hour postprandial period as shown on CGM
Timepoint [4] 320834 0
Measured over 4 hours by CGM
Secondary outcome [5] 320835 0
Time to peak glucose level in the 4 hour glucose period measured using CGM
Timepoint [5] 320835 0
Measured at 30 minute intervals for 4 hours by CGM

Eligibility
Key inclusion criteria
Ages 8-40 years
Type 1 Diabetes for <1 year,
HbA1c<8.1% (64 mmol/mol)
BMI <91st centile
No other major medical conditions or complications
Using insulin pump therapy
Minimum age
8 Years
Maximum age
40 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Presence of diabetes complications
Other major medical conditions
HbA1c >8.0% (64 mmol/mol)
Unwillingness/inability to follow to follow protocol
BMI >91st centile

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
Differences in mean glucose excursions at a single time point will be tested using generalised linear mixed models (using a linear regression model but allowing for the correlation of repeated measurements on the same subjects).
P values <0.05 will be considered statistically significant. Statistical support for data analysis will be provided by Clinical Research Design, IT and Statistical Support.
Sample size was calculated to provide 80% power at the 0,05% significance level, allowing for 10% missing data. This Sample size is based on previous published studies by our research group.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5281 0
John Hunter Children's Hospital - New Lambton
Recruitment hospital [2] 15956 0
John Hunter Hospital - New Lambton
Recruitment hospital [3] 15957 0
Gosford Hospital - Gosford
Recruitment postcode(s) [1] 29450 0
2250 - Gosford
Recruitment postcode(s) [2] 29449 0
2305 - New Lambton
Recruitment postcode(s) [3] 12743 0
2310 - Hunter Region

Funding & Sponsors
Funding source category [1] 292897 0
Hospital
Name [1] 292897 0
John Hunter Children's Hospital Charitable Trust
Address [1] 292897 0
C/- Hunter Medical Research Institute
Lot 1 Kookaburra Circuit
New Lambton Heights NSW 2310
Country [1] 292897 0
Australia
Primary sponsor type
Other
Name
Hunter Medical Research Institute
Address
Lot 1 Kookaburra Circuit
New Lambton Heights NSW 2310
Country
Australia
Secondary sponsor category [1] 291641 0
None
Name [1] 291641 0
Address [1] 291641 0
Country [1] 291641 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294396 0
Hunter New England Research Ethics Committee
Ethics committee address [1] 294396 0
Research Support and Development Office
District Headquarters, Administration Building
Lookout Road,
New Lambton NSW 2305
Ethics committee country [1] 294396 0
Australia
Date submitted for ethics approval [1] 294396 0
16/03/2016
Approval date [1] 294396 0
04/04/2016
Ethics approval number [1] 294396 0

Summary
Brief summary
To properly manage type 1 diabetes (T1DM), individuals are required to measure blood glucose levels regularly and adjust the amount of insulin to be given accordingly. This is done by matching the insulin doses to the carbohydrate content of a meal.
Recent studies have shown that meals high in dietary protein may cause postprandial hyperglycaemia. The paediatric diabetes research team at the John Hunter Children’s hospital published a study demonstrating that meal protein content can significantly affect postprandial blood glucose levels. More recently, our group have published a further study, looking at the impact of pure protein- independent of carbohydrate and fat- on postprandial blood glucose levels in T1DM. We are now in the process of completing a further study that was designed to investigate the effect of consuming protein with carbohydrate only (no fat) on postprandial blood glucose levels and have demonstrated a dose response to increasing amounts of protein when consumed with carbohydrate.
These findings have led to recommendations to give additional insulin for meals high in protein to avoid postprandial hyperglycaemic excursions. However, at the present time there is still insufficient data regarding how to safely and effectively calculate and deliver mealtime insulin doses for protein.
Therefore, we need to conduct further research in order to determine a safe and effective insulin dosing algorithm for meals high in protein.
Trial website
N/A
Trial related presentations / publications
Parts of this study were presented at the American Diabetes Association Annual Scientific Meeting in San Francisco, CA. USA in June 2019.
Public notes

Contacts
Principal investigator
Name 63590 0
A/Prof Bruce King
Address 63590 0
John Hunter Children's Hospital
Department of Paediatric Diabetes and Endocrinology
Locked Bag 1, HMRC
NSW 2310
Country 63590 0
Australia
Phone 63590 0
+61 249858634
Fax 63590 0
Email 63590 0
bruce.king@hnehealth.nsw.gov.au
Contact person for public queries
Name 63591 0
Ms Megan Paterson
Address 63591 0
John Hunter Children's Hospital
Department of Paediatric Diabetes and Endocrinology
Locked Bag 1, HMRC
NSW 2310
Country 63591 0
Australia
Phone 63591 0
+61 249855641
Fax 63591 0
Email 63591 0
megan.paterson@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 63592 0
Ms Megan Paterson
Address 63592 0
John Hunter Children's Hospital
Department of Paediatric Diabetes and Endocrinology
Locked Bag 1, HMRC
NSW 2310
Country 63592 0
Australia
Phone 63592 0
+61 2495855641
Fax 63592 0
Email 63592 0
megan.paterson@hnehealth.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
CGM traces where participants have consented
When will data be available (start and end dates)?
Data will be available when the manuscript is published
No end date determined.
Available to whom?
De indentifed data will be available to the readers of the publication
Available for what types of analyses?
For a graph in the publication
How or where can data be obtained?
Manuscript is currently in preparation
Data will be available by emailing the principal investigator Professor Bruce King
bruce.king@health.,nsw.gov.au
What supporting documents are/will be available?
Ethical approval
How or where can supporting documents be obtained?
Type [1] 7060 0
Ethical approval
Citation [1] 7060 0
Link [1] 7060 0
Email [1] 7060 0
Other [1] 7060 0
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary