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Trial registered on ANZCTR


Registration number
ACTRN12615000137594
Ethics application status
Approved
Date submitted
30/01/2015
Date registered
12/02/2015
Date last updated
24/10/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of the Impact of Exercise on the Performance of an Artificial Pancreas
Scientific title
Evaluation of the Impact of Exercise on the Performance of an Artificial Pancreas in Adults with Type 1 Diabetes.
Secondary ID [1] 285983 0
None
Universal Trial Number (UTN)
U1111-1166-1659
Trial acronym
None
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes 293923 0
Condition category
Condition code
Metabolic and Endocrine 294227 294227 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This two staged randomised crossover study involves people with type 1 diabetes who are established on insulin pump therapy and have glucose sensing experience. The study aims to examine the performance of an integrated "artificial pancreas" challenged by aerobic and anaerobic exercise in people with type 1 diabetes therapy and with glucose sensor experience.

All participants will undertake the aerobic and anaerobic exercise stages in random order. Following clinical assessment, each participant will undergo cardiopulmonary testing to determine their maximal amount of oxygen consumed during exercise (VO2 max as ml/kg/min), maximal exercise capacity (Watts) and anaerobic threshold. Subsequently there will be a ~6 day run-in period when participants wear glucose sensors and the study pump (without insulin delivery from this pump), while continuing their usual insulin regimen via their own insulin pump. The aerobic exercise protocol will be conducted on a stationary bicycle with 5 minutes of warm-up, followed by 40 minutes of steady-state exercise at 20% below anaerobic threshold. The anaerobic exercise protocol is high intensity interval training with 5 minutes of warm-up, then 6 repetitions of 4 minutes of exercise at an intensity halfway between their anaerobic threshold and maximal intensity, followed by 2 minutes of rest (an additional 4 minutes rest will be provided between the 3rd and 4th repetitions).

On the morning of the exercise study days, participants will have an early morning light breakfast (40g of carbohydrate), preceded by an insulin bolus via their own pump to account for the carbohydrate of the meal. The participants will commence their exercise program ~3 hours after arrival at the Clinical Trial Centre, and venous blood samples will be collected at 15 minute intervals from 1 hour prior to exercise until 2 hours after exercise completion to assess insulin and counter-regulatory hormones. Participants will resume their usual insulin regimen via their own insulin pump at the conclusion of each stage.

Participants will return to the Clinical Trial Centre approximately 2 weeks later to undertake the alternate exercise regimen, preceded by the run-in period.
Intervention code [1] 290958 0
Treatment: Devices
Intervention code [2] 291029 0
Treatment: Drugs
Intervention code [3] 291129 0
Treatment: Other
Comparator / control treatment
We are comparing the effectiveness of an "Artificial Pancreas" in both aerobic and anaerobic exercise.
Control group
Active

Outcomes
Primary outcome [1] 294034 0
Safety: Episodes of hypoglycaemia (blood glucose < 4.0mmol/L for at least 15 minutes duration).
Timepoint [1] 294034 0
Monitored every 5 minutes from 1 hour prior to exercise, until 2 hours post exercise in each study stage.
Primary outcome [2] 294035 0
Efficacy: Continuous glucose monitoring % (CGM) time spent in target glycaemia (4.0-8.0 mmol/L and 4.0-10.0 mmol/L).
Timepoint [2] 294035 0
Monitored every 5 minutes from 1 hour prior to exercise, until 2 hours post exercise in each study stage.
Secondary outcome [1] 312374 0
Episodes of major hypoglycaemia requiring third party assistance.
Timepoint [1] 312374 0
Monitored every 5 minutes from 1 hour prior to exercise, until 2 hours post exercise in each study stage.
Secondary outcome [2] 312376 0
Episodes of hyperglycaemia (blood glucose > 10.0mmol/L) with blood ketones > 0.4 mmol/L.
Timepoint [2] 312376 0
Monitored every 15 minutes from 1 hour prior to exercise, until 2 hours post exercise in each study stage.
Secondary outcome [3] 312377 0
Continuous glucose monitoring % (CGM) time spent in hyperglycaemia (>10.0 mmol/L) and hypoglycaemia (<4.0 mmol/L).
Timepoint [3] 312377 0
Monitored every 5 minutes from 1 hour prior to exercise, until 2 hours post exercise in each study stage.
Secondary outcome [4] 312379 0
Continuous glucose monitoring (CGM) time and area under the curve (AUC) spent above target range (> 10.0 mmol/L).
Timepoint [4] 312379 0
Monitored every 5 minutes from 1 hour prior to exercise, until 2 hours post exercise in each study stage.
Secondary outcome [5] 312381 0
Continuous glucose monitoring (CGM) time and area under the curve (AUC) spent below target range (< 4.0 mmol/L)
Timepoint [5] 312381 0
Monitored every 5 minutes from 1 hour prior to exercise, until 2 hours post exercise in each study stage.
Secondary outcome [6] 312382 0
Glycaemic variability as determined by mean amplitude of glycaemic excursions (MAGE) and Standard deviations (SD).
Timepoint [6] 312382 0
Monitored every 5 minutes from 1 hour prior to exercise, until 2 hours post exercise in each study stage.
Secondary outcome [7] 312383 0
Laboratory assay for counter-regulatory hormones (Free insulin, glucose, growth hormone, cortisol and catecholamines).
Timepoint [7] 312383 0
Monitored every 15 minutes from 1 hour prior to exercise, until 2 hours post exercise in each study stage.

Eligibility
Key inclusion criteria
-Age > 18 years
-Type 1 Diabetes (confirmed by fasting C-peptide level < 50 pmol/L)
-Insulin pump therapy for at least 6 months
-HbA1c < 9.0%
-Experience with a glucose sensor
-Established insulin pump therapy parameters
-Ability to insert/change sensor
-Ability to undertake exercise as per protocol
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Requiring > 150 units of insulin/day
-Diabetic ketoacidosis within the past 4 weeks
-Hypoglycaemic unawareness (Gold score >4) while on Sensor Augmented Pump Therapy (SAPT) or > 2 severe hypoglycaemic episodes within the last 12 months
-Pregnancy
-Renal impairment (eGFR < 60ml/min/1.73m2)
-Current or recent (<4 weeks) oral or inhaled steroid therapy
-Dermatological conditions involving the region of device insertion
-Ischaemic heart disease or peripheral vascular disease precluding exercise
-Physical limitations (e.g. impaired vision) that would compromise operation of the Closed Loop system

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 random allocation (i.e. equal numbers in both groups)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
This is an exploratory study. There is an absence of available data allowing the calculation of statistical power. The data generated by this study will enable power calculations for future research.

Descriptive statistics will be used to describe safety and efficacy parameters. A formal statistical comparison will be used to compare time spent within target glucose range for each of the two exercise modalities. A qualitative analysis will be performed examining changes in circulating free insulin and counter-regulatory hormones in response to the two different forms of exercise.

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)
VIC
Recruitment hospital [1] 3333 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 9122 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 290572 0
Hospital
Name [1] 290572 0
St Vincent's Hospital
Address [1] 290572 0
41 Victoria Parade
Fitzroy VIC 3065
Country [1] 290572 0
Australia
Funding source category [2] 290573 0
Commercial sector/Industry
Name [2] 290573 0
Medtronic Diabetes
Address [2] 290573 0
18000 Devonshire Street
Northridge CA 91325
Country [2] 290573 0
United States of America
Primary sponsor type
Hospital
Name
St Vincents Hospital
Address
41 Victoria Parade
Fitzroy VIC 3065
Country
Australia
Secondary sponsor category [1] 289262 0
University
Name [1] 289262 0
University of Melbourne
Address [1] 289262 0
29 Regent Street
Fitzroy VIC 3065
Country [1] 289262 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292213 0
St Vincent's Hospital Melbourne
Ethics committee address [1] 292213 0
Research Governance Unit
Level 5, Mary Aikenhead Building
27 Victoria Parade
Fitzroy VIC 3065
Ethics committee country [1] 292213 0
Australia
Date submitted for ethics approval [1] 292213 0
Approval date [1] 292213 0
12/01/2015
Ethics approval number [1] 292213 0
HREC-D 152/14

Summary
Brief summary
Insulin delivery via an insulin pump can mimic the normal action of the pancreas more closely than multiple daily injections of short and long acting insulin. With the development of continuous glucose monitoring devices, glucose levels can be measured continuously over 24 hours. These two devices have now been linked by a computer to create an “artificial pancreas” or Closed Loop system. The computer’s function is to calculate accurately the amount of insulin to be delivered by the pump based on the sensor glucose readings. Overnight Closed Loop systems have been tested in both children and adults with Type 1 diabetes. Overall, the results show that the systems are safe and effective. However, important gaps in our knowledge remain to be explored. For example, while exercise is healthy for people with diabetes it can result in unpredictable changes in glucose levels that may challenge an artificial pancreas. In addition, different types of exercise have differing effects on glucose levels in people with Type 1 diabetes. Short intense bursts of exercise (anaerobic exercise) may initially increase glucose levels while less intense exercise (aerobic exercise) tends to reduce glucose levels.

This study aims to collect information about how well the Closed Loop system is able to control glucose levels of people with type 1 diabetes when they undertake aerobic and anaerobic exercise. Outcomes of interest will include the risk of hypoglycaemia and time in healthy glucose range. Insulin and counter-regulatory hormones will also be measured providing insights into changes in glucose levels with exercise in Type 1 diabetes patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 54106 0
A/Prof David O'Neal
Address 54106 0
Department of Endocrinology & Diabetes, St Vincent's Hospital Melbourne, 35 Victoria Parade Fitzroy VIC 3065
Country 54106 0
Australia
Phone 54106 0
+61 3 9231 2211
Fax 54106 0
Email 54106 0
dno@unimelb.edu.au
Contact person for public queries
Name 54107 0
Dr Sybil McAuley
Address 54107 0
Department of Endocrinology & Diabetes, St Vincent's Hospital Melbourne, 35 Victoria Parade Fitzroy VIC 3065
Country 54107 0
Australia
Phone 54107 0
+61 3 9231 2211
Fax 54107 0
Email 54107 0
sybil.mcauley@svha.org.au
Contact person for scientific queries
Name 54108 0
Dr Sybil McAuley
Address 54108 0
Department of Endocrinology & Diabetes, St Vincent's Hospital Melbourne, 35 Victoria Parade Fitzroy VIC 3065
Country 54108 0
Australia
Phone 54108 0
+61 3 9231 2211
Fax 54108 0
Email 54108 0
sybil.mcauley@svha.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary