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Trial registered on ANZCTR


Trial ID
ACTRN12613000581763
Ethics application status
Approved
Date submitted
21/05/2013
Date registered
23/05/2013
Date last updated
7/06/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
The impact of exercise and exercise-related reductions in insulin pump basal delivery on blood insulin levels in type 1 diabetes
Scientific title
The impact of exercise and exercise-related reductions in insulin pump basal delivery on circulating insulin levels in type 1 diabetes
Secondary ID [1] 282529 0
Nil known
Universal Trial Number (UTN)
U1111-1143-2748
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 289193 0
Condition category
Condition code
Metabolic and Endocrine 289521 289521 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Two-stage randomised crossover study, with a 1-8 week interval between stages. Stage 1 (comparator): following an overnight fast and stable baseline subcutaneous insulin infusion rate for at least 6 hours, a 50% basal rate reduction will be instituted and the participant will be monitored at rest for 210 minutes. Venous samples will be collected for plasma insulin and glucose levels at 15 minute intervals from 60 minutes prior to the rate reduction until 210 minutes after. Stage 2 (intervention): protocol as per stage 1, with the addition of a 30 minute standardised moderate-intensity exercise protocol starting 60 minutes after the basal rate reduction. Exercise will be performed on a stationary bicycle, with target workload 65-70% age-predicted maximal heart rate.

The baseline insulin infusion rate will be individualised, and equal to the usual overnight rate of each participant. The total dose of subcutaneous insulin infused during the 210 minute intervention period will be between 0.8 units and 2.5 units (depending on the insulin requirements of the individual). Standardised insulin pump, aspart insulin, pump consumables and line change protocol will be used for each study stage, and participants will resume their usual insulin and insulin pump at the conclusion of each stage.
Intervention code [1] 287190 0
Treatment: Devices
Intervention code [2] 287191 0
Treatment: Drugs
Comparator / control treatment
No exercise (Stage 1)
Control group
Active

Outcomes
Primary outcome [1] 289615 0
The impact of moderate-intensity exercise, associated with a prior reduction in basal insulin delivery, on changes in circulating insulin levels. Plasma free insulin levels will be measured via radioimmunoassay (plasma will be pre-treated with polyethylene glycol to precipitate bound insulin when antibodies are present).
Timepoint [1] 289615 0
Plasma insulin levels will be assessed at 15 minute intervals from 60 minutes prior to the basal insulin rate reduction until 210 minutes after the reduction.
Secondary outcome [1] 302872 0
The impact of moderate-intensity exercise, associated with a prior reduction in basal insulin delivery, on changes in plasma glucose levels. Plasma glucose concentrations will be measured via the glucose oxidase method.
Timepoint [1] 302872 0
Plasma glucose levels will be assessed at 15 minute intervals from 60 minutes prior to the basal insulin rate reduction until 210 minutes after the reduction.
Secondary outcome [2] 302877 0
The impact of moderate-intensity exercise, associated with a prior reduction in basal insulin delivery, on changes in interstitial glucose levels. Interstitial glucose will be measured using a continuous glucose monitoring device with a small sensor inserted under the skin for the duration of each study stage.
Timepoint [2] 302877 0
Interstitial glucose levels will be assessed continuously from at least 24 hours prior to the basal insulin rate reduction until 210 minutes after the reduction.
Secondary outcome [3] 302878 0
The impact of moderate-intensity exercise, associated with a prior reduction in basal insulin delivery, on the requirement for intravenous dextrose to be administered to either avoid or treat hypoglycaemia (defined by venous glucose <4.0 mmol/L and/or symptoms of hypoglycaemia).
Timepoint [3] 302878 0
Venous glucose will be measured via glucose meter at 15 minute intervals (or more frequently if clinically indicated) from 60 minutes prior to the basal insulin rate reduction until 210 minutes after the reduction.

Eligibility
Key inclusion criteria
Clinical diagnosis of type 1 diabetes, managed with insulin pump therapy for minimum of 3 months, established insulin:carbohydrate ratio, established insulin sensitivity factor, established basal insulin delivery profile including overnight basal rate between 0.50-1.40 units per hour (without significant overnight variation), able to tolerate moderate-intensity exercise.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Symptoms of ischaemic heart disease or known cardiac condition precluding moderate-intensity exercise, ischaemic changes on electrocardiogram, episode of diabetic ketoacidosis or severe hypoglycaemia (requiring third party assistance) within the last month, pregnant or planned pregnancy within study period, renal impairment (estimated glomerular filtration rate <60 mL per minute), body mass index <18 or >32, adverse skin condition in the area of cannula or device placement, allergy to insulin aspart.

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
Phase 4
Type of endpoint(s)
Pharmacokinetics / pharmacodynamics
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.

Comparisons by paired t-tests and generalised linear modelling will be performed. The changes in insulin level within stage 1 versus stage 2 will be compared. Insulin level changes from baseline will be compared between stages 1 and 2 following completion of the exercise protocol.

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] 1036 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 6898 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 287309 0
Charities/Societies/Foundations
Name [1] 287309 0
Australian Diabetes Society
Address [1] 287309 0
145 Macquarie Street
Sydney NSW 2000
Country [1] 287309 0
Australia
Funding source category [2] 287310 0
Charities/Societies/Foundations
Name [2] 287310 0
Hugh D T Williamson Foundation
Address [2] 287310 0
c/- ANZ Trustees
GPO Box 389
Melbourne VIC 3001
Country [2] 287310 0
Australia
Funding source category [3] 287311 0
Charities/Societies/Foundations
Name [3] 287311 0
Lynne Quayle Charitable Trust
Address [3] 287311 0
c/- Equity Trustees
GPO Box 2307
Melbourne VIC 3001
Country [3] 287311 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital Melbourne
Address
41 Victoria Parade
Fitzroy VIC 3065
Country
Australia
Secondary sponsor category [1] 286060 0
University
Name [1] 286060 0
University of Melbourne
Address [1] 286060 0
29 Regent Street
Fitzroy VIC 3065
Country [1] 286060 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289284 0
St Vincent's Hospital Melbourne
Ethics committee address [1] 289284 0
Research Governance Unit
Level 5, Mary Aikenhead Building
27 Victoria Parade
Fitzroy VIC 3065
Ethics committee country [1] 289284 0
Australia
Date submitted for ethics approval [1] 289284 0
Approval date [1] 289284 0
10/05/2013
Ethics approval number [1] 289284 0
#056/13

Summary
Brief summary
Insulin pumps are increasingly being used to deliver insulin for people with type 1 diabetes. The two main components of insulin pump delivery are firstly "bolus" insulin, used with meals or to correct high glucose levels, and secondly "basal" insulin which provides the background insulin requirements. The rate of basal insulin delivered is adjustable, and may vary according to the time of day, stress, illness or exercise. Basal insulin rate reductions are typically made by patients prior to exercise to account for changing insulin requirements that occur with physical activity.

Information regarding the effects of exercise, and exercise-related changes in basal insulin rate, on insulin and glucose levels is essential to guide clinical decision-making. The purpose of this study is to investigate the impact of exercise, preceded by a major reduction in basal insulin delivery, on insulin levels and associated glucose levels.
Trial website
Trial related presentations / publications
Insulin pump basal adjustment for exercise in type 1 diabetes: a randomised crossover study. Diabetologia 2016. http://www.ncbi.nlm.nih.gov/pubmed/27168135
Public notes

Contacts
Principal investigator
Name 40110 0
Dr Sybil McAuley
Address 40110 0
Department of Endocrinology & Diabetes,
St Vincent's Hospital Melbourne,
35 Victoria Parade
Fitzroy VIC 3065
Country 40110 0
Australia
Phone 40110 0
+61 3 9288 2211
Fax 40110 0
Email 40110 0
sybil.mcauley@svhm.org.au
Contact person for public queries
Name 40111 0
Dr Sybil McAuley
Address 40111 0
Department of Endocrinology & Diabetes,
St Vincent's Hospital Melbourne,
35 Victoria Parade
Fitzroy VIC 3065
Country 40111 0
Australia
Phone 40111 0
+61 3 9288 2211
Fax 40111 0
Email 40111 0
sybil.mcauley@svhm.org.au
Contact person for scientific queries
Name 40112 0
Dr Sybil McAuley
Address 40112 0
Department of Endocrinology & Diabetes,
St Vincent's Hospital Melbourne,
35 Victoria Parade
Fitzroy VIC 3065
Country 40112 0
Australia
Phone 40112 0
+61 3 9288 2211
Fax 40112 0
Email 40112 0
sybil.mcauley@svhm.org.au