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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

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]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Type 1 Diabetes Mellitus

Condition category

Condition code

Metabolic and Endocrine

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]

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]

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]

CGM for 4 hours postprandially.

Secondary outcome [1]

Number of hypoglycaemic events in the 4 hour postprandial period (defined as BGL’s <3.5 mmol/l) assessed by CGM

Timepoint [1]

Measured for 4 hours postprandially by CGM

Secondary outcome [2]

Postprandial hyperglycaemia (defined as BGL’s >10.1 mmol/l) in the 4 hour postprandial period measured by CGM

Timepoint [2]

Measured by CGM for 4 Hours postprandially

Secondary outcome [3]

Glucose excursions at 30 minute intervals for the 4 hour postprandial period by CGM

Timepoint [3]

Assessed every 30 minutes from completion of meal for 4 hours by CGM

Secondary outcome [4]

Peak glucose level during the 6 hour postprandial period as shown on CGM

Timepoint [4]

Measured over 4 hours by CGM

Secondary outcome [5]

Time to peak glucose level in the 4 hour glucose period measured using CGM

Timepoint [5]

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

Sex

Both males and females

Can healthy volunteers participate?

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

4/04/2016

Actual

4/04/2016

Date of last participant enrolment

Anticipated

31/03/2017

Actual

5/11/2018

Date of last data collection

Anticipated

Actual

5/11/2018

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

John Hunter Children's Hospital - New Lambton

Recruitment hospital [2]

John Hunter Hospital - New Lambton

Recruitment hospital [3]

Gosford Hospital - Gosford

Recruitment postcode(s) [1]

2310 - Hunter Region

Recruitment postcode(s) [2]

2305 - New Lambton

Recruitment postcode(s) [3]

2250 - Gosford

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

John Hunter Children's Hospital Charitable Trust

Address [1]

C/- Hunter Medical Research Institute
Lot 1 Kookaburra Circuit
New Lambton Heights NSW 2310

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Hunter New England Research Ethics Committee

Ethics committee address [1]

Research Support and Development Office
District Headquarters, Administration Building
Lookout Road,
New Lambton NSW 2305

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/03/2016

Approval date [1]

04/04/2016

Ethics approval number [1]

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

A/Prof Bruce King

Address

John Hunter Children's Hospital
Department of Paediatric Diabetes and Endocrinology
Locked Bag 1, HMRC
NSW 2310

Country

Australia

Phone

+61 249858634

Fax

[email protected]

Contact person for public queries

Name

Megan Paterson

Address

John Hunter Children's Hospital
Department of Paediatric Diabetes and Endocrinology
Locked Bag 1, HMRC
NSW 2310

Country

Australia

Phone

+61 249855641

Fax

[email protected]

Contact person for scientific queries

Name

Megan Paterson

Address

John Hunter Children's Hospital
Department of Paediatric Diabetes and Endocrinology
Locked Bag 1, HMRC
NSW 2310

Country

Australia

Phone

+61 2495855641

Fax

[email protected]

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?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
7060	Ethical approval					370133-(Uploaded-04-02-2020-11-43-45)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	High-protein meals require 30% additional insulin to prevent delayed postprandial hyperglycaemia.	2020	https://dx.doi.org/10.1111/dme.14308

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically