The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12616000729426p
Ethics application status
Submitted, not yet approved
Date submitted
31/05/2016
Date registered
2/06/2016
Date last updated
2/06/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Defining the relationship between carbohydrate amount and the dose of insulin
Scientific title
Defining the relationship between carbohydrate quantity and the dose of
subcutaneous insulin.
Secondary ID [1] 289343 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type one Diabetes Mellitus 298966 0
Hypoglycaemia 298967 0
Condition category
Condition code
Metabolic and Endocrine 299032 299032 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This research project will analyse the response of glucose levels after a predominantly carbohydrate based meal. Forty participants between 12 -30 years of age, with type one diabetes on intensive insulin therapy will be recruited. Participants will be fitted with the Animas G4 continuous glucose monitoring system (CGMS). Insulin dose will be calculated using the standard linear insulin to carb ratio for meals of 20, 50, 100 and 150g of carbohydrate, standardised for % of energy from carbohydrates, fat, protein. The planned meal will be a standard pancake recipe with a sucrose based topping for all four carbohydrate quantities with the carbohydrates coming mostly from flour, sugar and milk.

Prior to commencement of the study participants will complete a 1 - 2 week run-in period where their control and insulin to carb ratio will be optimised through telephone contact with the diabetes team. They will then attend a short approx half an hour visit to the research department at the hospital to be fitted and explained the CGMS.

The next day following the fitting of the CGMS the participant will then either attend the hospital or researchers will attend the participants home 4 mornings in a row to prepare the study meal, supervise insulin administration and meal consumption. The total required length of including the run in period will be 2 -3 weeks and approximately 1 -2 hours per day.

Insulin will be administered in their usual way (injection or pump) and sedentary activities and fasting will be undertaken unless food is required for hypoglycaemia in the 5 hours following meal consumption. The CGMS data from this post postprandial period will subsequently be analysed by researchers to determine whether the currently standard practice of using an insulin to carbohydrate ratio is effective across a range of sized carbohydrate meals.
Intervention code [1] 294912 0
Other interventions
Comparator / control treatment
The study design is a with-in subject, randomised, repeated measure trial. The study involves the provision of test meals given on four consecutive days at breakfast in the same subjects. Each participant will serve as his/her own control.
Control group
Active

Outcomes
Primary outcome [1] 298496 0
Mean percentage of time in glucose target (4 – 10 mmol/L) using a continuous glucose monitoring system.
Timepoint [1] 298496 0
average data from the five hour post postprandial period on four different days after four different meals will be analysed
Secondary outcome [1] 324374 0
Hypoglycaemia (defined as less than or equal to 3.9 confirmed upon finger prick) during the five hour postprandial period.
Timepoint [1] 324374 0
Average data from the five hour post postprandial period on four different days after four different sized meals will be analysed

Eligibility
Key inclusion criteria
Patients will have been diagnosed with T1DM for >/= one year
Insulin pump or multiple daily injections using an ICR for >/= 6 months
HbA1c of < /= 8%
Non-obese weight (< /=97th %ile for children, BMI <30kg/m2 for adults)
Minimum age
12 Years
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any pre-existing complications of diabetes, such as gastroparesis
Any co existing food intolerances, allergies and medical conditions such as coeliac disease

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
Type of endpoint(s)
Statistical methods / analysis
The primary outcome of time in range will be analysed using repeated measurements on participants a linear mixed model to take account of the repeated measurements on subjects. The outcome in the model will be the percentage of blood glucose readings for an individual on a given day that are between 4 and 10 mmol/L in the five hour period after the meal. The predictor variable of interest will be the meal type (A – D), which will be included as a factor variable in the model. The model will be fitted using restricted maximum likelihood and a likelihood ratio statistic will be used to determine if there is a statistically significant difference in the outcome of interested between meal types. If the p-value from the likelihood ratio statistic is less than 0.05 we will examine the Wald statistics to identify where the difference lies. A logistic regression model fitted within a generalised estimating equation framework will be used to determine if there is a statistically significant difference in the occurance of hypoglycaemic events between the meal types.

Based on data from our previous studies we expect the standard deviation of the difference between two meal types in the percentage of time a subject is within range to be about 40 percent. Therefore 34 subjects will provide the study with approximately 80% power to find a difference of 20 percent between any two meals at the 5% significance level. To allow for missing data due to monitor failure etc. we will recruit 40 participants.

Recruitment
Recruitment status
Not yet recruiting
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,WA
Recruitment hospital [1] 5873 0
Princess Margaret Hospital - Subiaco
Recruitment hospital [2] 5874 0
John Hunter Children's Hospital - New Lambton

Funding & Sponsors
Funding source category [1] 293722 0
Charities/Societies/Foundations
Name [1] 293722 0
Juvenille Diabetes Research Foundation
Address [1] 293722 0
181 Main Street Osborne Park , WA, 6017
Country [1] 293722 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Telethon Kids Institiute
Address
100 Roberts Rd, Subiaco WA 6008
Country
Australia
Secondary sponsor category [1] 292552 0
Hospital
Name [1] 292552 0
John Hunter Children's Hospital
Address [1] 292552 0
Kookaburra Circuit, New Lambton Heights NSW
Country [1] 292552 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 295153 0
The Hunter New England Human Research Ethics Committee
Ethics committee address [1] 295153 0
Hunter New England Human Research Ethics Committee
Hunter New England Local Health District
Locked Bag 1
New Lambton NSW 2305
Ethics committee country [1] 295153 0
Australia
Date submitted for ethics approval [1] 295153 0
29/05/2016
Approval date [1] 295153 0
Ethics approval number [1] 295153 0
Ethics committee name [2] 295154 0
Princess Margaret Hospital Human Research Ethics Committee
Ethics committee address [2] 295154 0
Princess Margaret Hospital
Roberts Road, Subiaco, Perth
Western Australia 6008

Ethics committee country [2] 295154 0
Australia
Date submitted for ethics approval [2] 295154 0
12/04/2016
Approval date [2] 295154 0
Ethics approval number [2] 295154 0

Summary
Brief summary
Patients with type one diabetes typically carbohydrate count and use an insulin to carbohydrate ratio (ICR) to dose their insulin. This ratio assumes a linear relationship between carbohydrate quantities to be consumed and the insulin required to maintain blood sugar levels after a meal. Recent research and reports from families with type 1 diabetes raise the question of the validity of this linear model. This study aims to define the relationship between carbohydrate quantity and the dose of subcutaneous insulin. More specifically, to demonstrate that the current linear ICR approach is too steep resulting in increased events of low blood sugar levels as the carbohydrate content increases.

This research project will analyse the response of blood glucose levels after a predominantly carbohydrate based meal. Forty participants between 12 -30 years of age, with type one diabetes on intensive insulin therapy will be recruited. Participants will be fitted with a continuous glucose monitoring system (CGMS). Insulin dose will be calculated using the standard linear ICR using study liquid-meals of 20, 50, 100 and 150g of carbohydrate controlled with similar proportions of fats and protein on four consecutive days (one per day). CGMS data will be analysed to determine whether the relationship between carbohydrate intake and insulin requirements is indeed linear.

It is hoped this study will provide important information in the management of type 1 diabetes in both adults and children. Results will assist in building on planned future studies of trialing a non-linear ICR if the hypothesis is supported. This research will be used in our day to day management of patients and guide the development of clinical guidelines to help minimise the occurrence of hypoglycaemia and blood glucose fluctuations after eating.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66322 0
A/Prof Bruce King
Address 66322 0
John Hunter Childrens Hospital
Locked Bag 1
Hunter Regional Mail Centre
Newcastle NSW 2310
Country 66322 0
Australia
Phone 66322 0
+61 2 49855429
Fax 66322 0
Email 66322 0
Bruce.King@hnehealth.nsw.gov.au
Contact person for public queries
Name 66323 0
Miss Natalie Del Borrello
Address 66323 0
Princess Margaret Hospital
Roberts Road, Subiaco, Perth
Western Australia 6008
Country 66323 0
Australia
Phone 66323 0
+61 8 93407905
Fax 66323 0
Email 66323 0
natalie.delborrello@health.wa.gov.au
Contact person for scientific queries
Name 66324 0
Miss Natalie Del Borrello
Address 66324 0
Princess Margaret Hospital
Roberts Road, Subiaco, Perth
Western Australia 6008
Country 66324 0
Australia
Phone 66324 0
+ 61 8 93407905
Fax 66324 0
Email 66324 0
natalie.delborrello@health.wa.gov.au

No information has been provided regarding IPD availability
Summary results
No Results