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Trial registered on ANZCTR


Registration number
ACTRN12612000609853
Ethics application status
Not yet submitted
Date submitted
6/06/2012
Date registered
7/06/2012
Date last updated
7/06/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
What is the optimal insulin amplitude for a square wave bolus in people with type 1 diabetes
Scientific title
What is the optimal amplitude for a square wave bolus of insulin aspart in children and young people aged 7-35years to control postprandial hyperglycaemia (postprandial blood glucose excursion at 1 hour <3mmol/L)?
Secondary ID [1] 280638 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 286650 0
Condition category
Condition code
Metabolic and Endocrine 286940 286940 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Continuous subcutaneous insulin infusion with insulin aspart

6 different bolus doses based on participants' individual insulin:carbohydrate ratios.
Dose 1: Standard bolus (rapid infusion) determined using participant's insulin:carbohydrate ratio
Dose 2: Insulin dose determined using 100% of participant's individual insulin:carbohydrate ratio delivered over 2 hours
Dose 3: Insulin dose determined using 50% of participant's individual insulin:carbohydrate ratio delivered over 2 hours
Dose 4: Insulin dose determined using 33% of participant's individual insulin:carbohydrate ratio delivered over 2 hours
Dose 5: Insulin dose determined using 25% of participant's individual insulin:carbohydrate ratio delivered over 2 hours
Dose 6: Insulin dose determined using 17% of participant's individual insulin:carbohydrate ratio delivered over 2 hours

After these doses participant's will return their insulin pump to their normal individually determined basal rate

This is a crossover study where each participant will receive each of the doses on different days. The study will be run over 6 days with the participants being given each different dose with their breakfast meal. For the remainder of the day the participants will use their usual basal settings with their usual boluses for meals.
Intervention code [1] 285034 0
Treatment: Drugs
Comparator / control treatment
Dose 1 is standard dose of insulin aspart as determined using the participant's individual insulin:carbohydrate ratio delivered rapidly
Control group
Active

Outcomes
Primary outcome [1] 287286 0
Postprandial blood glucose excursion
Continuous glucose monitoring system (CGMS) will be inserted on day 1 of the study to continously assess participants' blood glucose levels
Timepoint [1] 287286 0
1 hour
Secondary outcome [1] 297831 0
Rate of maximal blood glucose increase
CGMS will be inserted on day 1 of the study to continously assess participants' blood glucose levels
Timepoint [1] 297831 0
4 hours
Secondary outcome [2] 297832 0
Percent time in target BGL range
CGMS will be inserted on day 1 of the study to continously assess participants' blood glucose levels
Timepoint [2] 297832 0
4 hours
Secondary outcome [3] 297833 0
Maximal blood glucose excursion
CGMS will be inserted on day 1 of the study to continously assess participants' blood glucose levels
Timepoint [3] 297833 0
4 hours
Secondary outcome [4] 297834 0
Time to maximal blood glucose excursion
CGMS will be inserted on day 1 of the study to continously assess participants' blood glucose levels
Timepoint [4] 297834 0
4 hours
Secondary outcome [5] 297835 0
Time until blood glucose returns to baseline
CGMS will be inserted on day 1 of the study to continously assess participants' blood glucose levels
Timepoint [5] 297835 0
4 hours
Secondary outcome [6] 297836 0
Hypoglycaemic events
CGMS will be inserted on day 1 of the study to continously assess participants' blood glucose levels
Participants will also record their own BGLs according to standard practice. Standard practice typically involves 3 pre-meal BGL tests per day with 1 test prior to bed time/at suppertime.
Timepoint [6] 297836 0
4 hours

Eligibility
Key inclusion criteria
Type 1 Diabetes Mellitus >/= 12 months
Insulin pump therapy >/= 6 months
Aged between 7 and 35 years
HbA1c </= 8% (no lower limit)
Minimum age
7 Years
Maximum age
35 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
BMI >91st percentile
Complications of their diabetes
Major medical problems

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)
Potential subjects approached at diabetic clinic and provided with information package and consent form.
Participants given computer generated code.
Code used for randomisation.
Participants give each of the 6 different doses and are randomised to which day to deliver each of the doses.
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Upon generation of code participants will have computer-generated randomisation to deliver each of the 6 bolus doses on 6 different days.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Participants act as their own control as each participant gives each of the 6 different bolus doses
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

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)

Funding & Sponsors
Funding source category [1] 285404 0
Commercial sector/Industry
Name [1] 285404 0
NovoNordisk Regional Support Scheme grant
Address [1] 285404 0
NovoNordisk Pharmaceutical Pty Ltd
Level 3
21 Solent Circuit
BAULKHAM HILLS NSW 2153
Country [1] 285404 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
NovoNordisk Regional Support Scheme grant
Address
NovoNordisk Pharmaceutical Pty Ltd
Level 3
21 Solent Circuit
BAULKHAM HILLS NSW 2153
Country
Australia
Secondary sponsor category [1] 284256 0
None
Name [1] 284256 0
Address [1] 284256 0
Country [1] 284256 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 287415 0
Ethics committee address [1] 287415 0
Ethics committee country [1] 287415 0
Date submitted for ethics approval [1] 287415 0
08/06/2012
Approval date [1] 287415 0
Ethics approval number [1] 287415 0

Summary
Brief summary
BACKGROUND:
In patients with type 1 diabetes insulin is required to control the rise in blood sugar levels that occurs after eating. Insulin boluses may be given in 3 main ways - a standard bolus (rapid bolus of insulin usually given just prior to a meal), a square wave bolus (a fixed dose of insulin given over a set period of time) or a dual wave bolus (a combination of the previous 2 boluses).

AIM:
To determine the amplitude (dose) required for a square wave insulin bolus of two hours duration to maintain blood glucose levels (glycaemic control) when a standard carbohydrate (60g) meal is eaten.


METHOD:
40 participants between the ages of 7 and 35 years with Type 1 Diabetes on insulin pump therapy will be recruited. The inclusion criteria are HbA1C </= 8%, Body Mass Index (BMI) <91st percentile, no complications of their diabetes and no other medical conditions. During a 1 week lead up to the study blood glucose control will be closely monitored. Participants will be contacted daily-2nd daily by a member of the research team. Adjustments may be made to the participant's insulin pump settings in conjunction with their treating endocrinologist. A continuous glucose monitoring system (CGMS) will be inserted on the first morning of the study. On this morning the participant will need to come to the hospital prior to breakfast. They will check their BGL 1 and 2 hours after insertion of CGMS for machine calibration. Participants will be provided with standard breakfast containing 60g of carbohydrate for each of the 6 days of the study. Insulin for the breakfast will be delivered as a square wave bolus over two hours starting just before the person starts eating. The bolus rate will be based on the participant's insulin: carbohydrate ratio and randomised each day to deliver a different percentage of this ratio (1:1 i.e 100% of the participant's insulin:carbohydrate dose for 2 hours, 1:2 i.e 50% of the participant's insulin:carbohydrate dose for 2 hours, 1:3, 1:4 and 1:6). The 6th bolus will be the participant’s standard bolus dose delivered as per usual practice. After the bolus is completed participants will return the pump to their usual basal rate. Participants should not eat until 4 hours after the test meal. Participants will self-monitor their blood glucose levels (BGLs) according to usual practice. If BGL is >18mmol/L at any time from >/= 4 hours after breakfast a correction bolus will be used. If the BGL goes below 3.5mmol/L or the participant has symptoms of hypoglycaemia at any time then they will eat 15 grams of carbohydrate.

OUTCOMES:
Primary outcome is the blood glucose excursion at 1 hour.
Secondary outcomes include maximal blood glucose increase, maximal blood glucose excursion, time to maximal blood glucose excursion, time in target blood glucose range, area under the curve and hypoglycaemic events.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34283 0
Address 34283 0
Country 34283 0
Phone 34283 0
Fax 34283 0
Email 34283 0
Contact person for public queries
Name 17530 0
Prudence Evans
Address 17530 0
John Hunter Children's Hospital
Locked Bag 1
Hunter Region Mail Centre
NSW 2310
Country 17530 0
Australia
Phone 17530 0
+61249855634
Fax 17530 0
Email 17530 0
prudence.evans@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 8458 0
Prudence Evans
Address 8458 0
John Hunter Children's Hospital
Locked Bag 1
Hunter Region Mail Centre
NSW 2310
Country 8458 0
Australia
Phone 8458 0
+61249855634
Fax 8458 0
Email 8458 0
prudence.evans@hnehealth.nsw.gov.au

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