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Trial registered on ANZCTR


Registration number
ACTRN12618000905268
Ethics application status
Approved
Date submitted
10/05/2018
Date registered
29/05/2018
Date last updated
29/10/2018
Date data sharing statement initially provided
29/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Advancing automated insulin delivery for exercise to improve the daily lives of people with type 1 diabetes
Scientific title
Assessing exercise-related parameters during closed-loop insulin delivery to advance closed-loop systems for people with type 1 diabetes
Secondary ID [1] 294046 0
Nil known
Universal Trial Number (UTN)
U1111-1209-3472
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 306590 0
Condition category
Condition code
Metabolic and Endocrine 305686 305686 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All procedures involving study participants will be undertaken by study doctors, nurses and scientists. Participants will be directly supervised by research personnel for all study activities in the clinical trial centre (CTC), including exercise. Maximal cardiopulmonary exercise testing (VO2max) will be assessed on a stationary bicycle over 15 min. Maximal strength (3-lift max) will be measured. Participants will be provided with study devices and receive education regarding their use. Transcutaneous glucose sensors will be worn for continuous glucose monitoring (CGM) during the study. A study insulin pump will be programmed with the participant’s individualised insulin delivery settings and paired with the CGM.

Participants will undertake three exercise stages in random order, separated by 1–4 weeks (timing determined by participant availability). The exercise intervention bouts within the respective stages are: (i) moderate-intensity exercise (MIE) on a stationary bicycle [32 min continuous exercise at 40% maximal intensity]; (ii) high-intensity interval exercise (HIIE) on a stationary bicycle [4 × 4 min intervals at 80% maximal intensity with 4 min rest between intervals]; and (iii) resistance exercise (RE) involving a circuit of five compound resistance exercises (e.g. leg press, seated row) each performed for 8-12 repetitions and completed 3 times (resistance weight at 80% 3–lift max).

Four days prior to each exercise bout, closed loop (CL) automated insulin delivery mode will be initiated on the insulin pump. Prior to each exercise bout, participants will eat a standardised lunch (with 40 g carbohydrate, 25 g protein and 10 g fat) at midday, then attend the CTC early afternoon. Accelerometers (wrist and ankle) and electrocardiogram leads will be attached, and an intravenous cannula will be inserted for sample collection. During the HIIE stage only, a prototype lactate sensor will be inserted subcutaneously in the anterior abdomen and attached to a recorder. Two hours prior to each exercise bout, the CL glucose target will be increased from 6.7 mmol/L to 8.3 mmol/L. Exercise will commence 4 h after the standardised lunch. If blood glucose is <7.0 mmol/L at 10 min pre-exercise, 15 g carbohydrate will be consumed. Ten min after exercise completion, the CL target will be decreased to 6.7 mmol/L. Non-arterialised venous samples will be collected at standardised intervals (starting 60 min pre-exercise and finishing 240 min post-exercise completion) for measurement of glucose, lactate, ketones, free insulin, adrenaline, noradrenaline, dopamine, cortisol, growth hormone and glucagon. Blood ketones will continue to be measured hourly until they are <0.4 mmol/L. A standardised meal (with 45 g carbohydrate, 30 g protein and 15 g fat) will be provided for consumption at 21:00 h, preceded by an insulin bolus as per participants’ usual individualised settings. After the meal, the intravenous cannula and accelerometers will be removed and the participant will depart the CTC. Participants will continue using CL for 6 days after each exercise bout.

CGM data will be recorded throughout the study. Heart rate will be monitored by electrocardiograph from 30 min before exercise until 60 min after exercise completion. Accelerometer data will be recorded during the CTC visit and downloaded after wear.
Intervention code [1] 300318 0
Treatment: Drugs
Intervention code [2] 300319 0
Treatment: Devices
Intervention code [3] 300320 0
Treatment: Other
Comparator / control treatment
Crossover study - all participants undertake each exercise intervention stage, with the exercise and post-exercise periods compared with rest.
Control group
Active

Outcomes
Primary outcome [1] 304781 0
Proportion of time spent with sensor glucose 3.9–10 mmol/L
Timepoint [1] 304781 0
0–14 h after commencement of each exercise bout (primary timepoint); during each exercise bout; 0–4 h after completion of each exercise bout; and 4–13 h after completion of each exercise bout
Secondary outcome [1] 343151 0
Proportion of time spent with sensor glucose <3.9 mmol/L for at least 15 min
Timepoint [1] 343151 0
0–14 h after commencement of each exercise bout; during each exercise bout; 0–4 h after completion of each exercise bout; and 4–13 h after completion of each exercise bout
Secondary outcome [2] 343152 0
Proportion of time spent with sensor glucose >10.0 mmol/L
Timepoint [2] 343152 0
0–14 h after commencement of each exercise bout; during each exercise bout; 0–4 h after completion of each exercise bout; and 4–13 h after completion of each exercise bout
Secondary outcome [3] 343167 0
Glucose variability measured by coefficient of variation
Timepoint [3] 343167 0
0–14 h after commencement of each exercise bout; during each exercise bout; 0–4 h after completion of each exercise bout; and 4–13 h after completion of each exercise bout
Secondary outcome [4] 343168 0
Sensor glucose positive incremental area under the curve (AUC) following the Wolever method
Timepoint [4] 343168 0
0–14 h after commencement of each exercise bout; during each exercise bout; 0–4 h after completion of each exercise bout; and 4–13 h after completion of each exercise bout
Secondary outcome [5] 343210 0
Change in plasma glucose levels
Timepoint [5] 343210 0
From 1 h prior to exercise commencement until 4 h post-exercise completion for each exercise bout
Secondary outcome [6] 347346 0
Change in plasma lactate levels
Timepoint [6] 347346 0
From 1 h prior to exercise commencement until 4 h post-exercise completion for each exercise bout
Secondary outcome [7] 347347 0
Change in blood ketone levels
Timepoint [7] 347347 0
From 1 h prior to exercise commencement until normalisation (up to 8 h post-exercise completion) for each exercise bout
Secondary outcome [8] 347348 0
Change in plasma insulin levels
Timepoint [8] 347348 0
From 1 h prior to exercise commencement until 4 h post-exercise completion for each exercise bout
Secondary outcome [9] 347349 0
Change in glucose counter-regulatory hormones levels
Timepoint [9] 347349 0
From 1 h prior to exercise commencement until 4 h post-exercise completion for each exercise bout
Secondary outcome [10] 347350 0
Change in heart rate (assessed by electrocardiogram)
Timepoint [10] 347350 0
From 1 h prior to exercise commencement until 4 h post-exercise completion for each exercise bout

Eligibility
Key inclusion criteria
Type 1 diabetes for >1 year
Insulin pump therapy for >6 months
HbA1c <9% (<75 mmol/mol)
Able to undertake high-intensity exercise
Minimum age
12 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Renal impairment with eGFR <45 mL/min/1.73 m^2
Insulin dose >150 units/day
Untreated cardiovascular disease
Diabetic ketoacidosis or systemic steroid therapy within past month
Severe visual impairment
Pregnancy
Untreated thyroid, adrenal or 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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Data from adults (aged 24-60 years) and adolescents (aged 12-18 years) will be analysed combined and separately. We estimate that with a two-sided p of 0.05, samples of n=30 adults and n=30 adolescents participating in each exercise modality will have 80% power to detect a standardised mean difference of 0.6 in the primary endpoint in each sub-group when using ANCOVA. Pairwise comparisons between the exercise stages will be performed using ANCOVA.

Recruitment
Recruitment status
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,VIC
Recruitment hospital [1] 10010 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [2] 10875 0
John Hunter Children's Hospital - New Lambton
Recruitment postcode(s) [1] 22620 0
2305 - New Lambton
Recruitment postcode(s) [2] 19336 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 10385 0
Canada
State/province [1] 10385 0

Funding & Sponsors
Funding source category [1] 298671 0
Charities/Societies/Foundations
Name [1] 298671 0
JDRF International and The Leona M. and Harry B. Helmsley Charitable Trust
Address [1] 298671 0
26 Broadway, 14th floor
New York, NY 10004
Country [1] 298671 0
United States of America
Primary sponsor type
Hospital
Name
St Vincent's Hospital Melbourne
Address
27 Victoria Pde
Fitzroy, VIC 3065
Country
Australia
Secondary sponsor category [1] 297840 0
Hospital
Name [1] 297840 0
John Hunter Children's Hospital
Address [1] 297840 0
Lookout Road
New Lambton, NSW 2305
Country [1] 297840 0
Australia
Secondary sponsor category [2] 298720 0
University
Name [2] 298720 0
York University
Address [2] 298720 0
4700 Keele Street
Toronto, ON M3J 1P3
Country [2] 298720 0
Canada

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299625 0
St Vincent's HREC
Ethics committee address [1] 299625 0
27 Victoria Pde
Fitzroy, VIC 3065
Ethics committee country [1] 299625 0
Australia
Date submitted for ethics approval [1] 299625 0
Approval date [1] 299625 0
19/04/2018
Ethics approval number [1] 299625 0

Summary
Brief summary
Participants with type 1 diabetes will undertake three exercise stages, in random order, while they receive automated insulin dosing delivered via an insulin pump. The types of exercise to be undertaken are: (i) moderate-intensity exercise; (ii) short bursts of high-intensity exercise; and (iii) resistance exercise using weights. The changes in biochemical parameters, body movement and heart rate during the three types of exercise will be compared. This information will ultimately be used to refine the computer program controlling automated insulin delivery for people with type 1 diabetes when they are exercising.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81078 0
Prof David O'Neal
Address 81078 0
University of Melbourne
St Vincent's Hospital Melbourne
29 Regent St
Fitzroy, VIC 3065
Country 81078 0
Australia
Phone 81078 0
+61 3 9231 2211
Fax 81078 0
Email 81078 0
dno@unimelb.edu.au
Contact person for public queries
Name 81079 0
Ms Catriona Sims
Address 81079 0
University of Melbourne
St Vincent's Hospital Melbourne
29 Regent St
Fitzroy, VIC 3065
Country 81079 0
Australia
Phone 81079 0
+61 3 9231 2211
Fax 81079 0
Email 81079 0
catriona.sims@unimelb.edu.au
Contact person for scientific queries
Name 81080 0
Dr Sybil McAuley
Address 81080 0
University of Melbourne
St Vincent's Hospital Melbourne
29 Regent St
Fitzroy, VIC 3065
Country 81080 0
Australia
Phone 81080 0
+61 3 9231 2211
Fax 81080 0
Email 81080 0
sybil@unimelb.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Undecided
What supporting documents are/will be available?
No other documents available
Summary results
No Results