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Trial registered on ANZCTR


Registration number
ACTRN12619001397101
Ethics application status
Approved
Date submitted
7/09/2019
Date registered
14/10/2019
Date last updated
5/03/2021
Date data sharing statement initially provided
14/10/2019
Date results information initially provided
5/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of reducing insulin versus eating carbohydrates on glycaemic control and performance with aerobic exercise in type 1 diabetes
Scientific title
The effects of reducing insulin versus eating carbohydrates on glycaemic control and performance with aerobic exercise in type 1 diabetes.
Secondary ID [1] 299135 0
Nil Known
Universal Trial Number (UTN)
U1111-1239-6201
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes 314202 0
Condition category
Condition code
Diet and Nutrition 312560 312560 0 0
Other diet and nutrition disorders
Metabolic and Endocrine 312856 312856 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
25 Male Participants (in groups of 5 participants at a time) will be performing a walking exercise for 45 mins on a standardized treadmill at a 1% gradient. The brisk walk will be determined by participants trying to maintain the speed of 7.24 kilometers per hour throughout the entire 45 min. Following the aerobic exercise, participants will perform a six-minute walk test which is a validated measure of predicted VO2 max and will serve as a performance test. This will be followed by a 7 days washout period and then the same group of participants will be repeating the above process for the crossover treatment.

Ninety minutes before the exercise all participants on continuous subcutaneous insulin infusion (CSII; known as insulin pump therapy) will start a 50% temporary basal rate reduction as per guidelines.

Sixty minutes before the exercise, all participants will eat a carbohydrate predominant mixed meal individualized to contain 0.66 g of carbohydrate/kg of body and 3.375 kcal/kg of body weight, meeting the requirements of both energy expenditure and exercise carbs guidelines

Participants in the reduced insulin group will administer 50% of their normal prandial dose of insulin immediately before the meal as a single bolus, with no combo or dual wave boluses allowed. Participants in the exercise carbs group will not administer any prandial insulin or adjust the doses of their basal insulin.

The first meal post exercise will be a pre-prepared lunch of sandwiches and fruit (equivalent to 1 g of carbohydrate/kg of body weight) will be provided.

Each patient will be provided with a Freestyle Libre reader and sensor to allow interstitial glucose levels to be measured by Flash Glucose Monitor (FGM) throughout the study period. The sensor will be inserted at least 36-48 hours before exercise day to ensure accurate calibration. Due to concerns over a several minute lag between changes in interstitial and blood glucose levels, Capillary Blood Glucose, Ketone and lactate levels will be measured on a calibrated glucometer at baseline and every 15 minutes whilst exercising as well as at baseline, at the completion of the aerobic exercise, and following completion of the 6-min walk test.

All treatment decisions will be based on CBG levels and not on FGM and will be administered by the research team in presence of a medical professional (Endocrinologist). All participants data of food intake will be recorded in a case record form for the night before, day of, and for the 48 hours following the study with the details of all meals, snacks and water consumed on a regular basis. Outside of these time frames, they will be allowed to consume their normal diets and there will be no strict and restrictive diet guidelines.
Intervention code [1] 315450 0
Treatment: Other
Comparator / control treatment
Comparator Intervention - Insulin reduction.

Ninety minutes before the exercise all participants on continuous subcutaneous insulin infusion (CSII; known as insulin pump therapy) will start a 50% temporary basal rate reduction as per guidelines.

Participants in the reduced insulin group will administer 50% of their normal prandial dose of insulin immediately before the meal as a single bolus, with no combo or dual wave boluses allowed.
Control group
Active

Outcomes
Primary outcome [1] 321248 0
The composite primary outcomes of the study are the time of glucose levels in target range (4-10 mmol/L), the time of glucose levels in hypoglycaemia (<4.0 mmol/L), the time of glucose levels in hyperglycaemia ( > 10.0 mmol/L). Both the outcomes will be assessed by measuring the capillary blood glucose using a glucometer and further assessed by laboratory assay of blood sample.
Timepoint [1] 321248 0
Monitored from the start of the exercise day (baseline), during (every 15 minutes of the exercise) and in the four hours following 45 minutes of aerobic exercise.
Secondary outcome [1] 374513 0
The composite secondary outcome is the effects on capillary Ketone and lactate levels.
Ketone and blood lactate as assessed by laboratory assay of blood sample.
Timepoint [1] 374513 0
Monitored from the start of the exercise day (baseline), during (every 15 minutes of the exercise) and in the four hours following 45 minutes of aerobic exercise.
Secondary outcome [2] 375366 0
The effects on predicted VO2 max as a marker of performance as assessed using the 6 minute walk test and using a heart rate monitor
Timepoint [2] 375366 0
Monitored from the start of the exercise day (baseline), during and in the four hours following 45 minutes of aerobic exercise.

Eligibility
Key inclusion criteria
Patients diagnosed with type 1 diabetes (T1D).
T1D Men (but not on testosterone replacement therapy)
Patients competent at self-management of all diabetes tasks
T1D patients who have an HbA1c of 45 - 90 mmol/mol (within the last 3 months)
T1D patients who are able to walk unaided for 45 mins at a fast pace (7 km/h)
T1D patients on treatment with a traditional insulin pump therapy
Minimum age
18 Years
Maximum age
60 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Type 1 diabetes (T1D) patients with any co-morbidity that could make exercise unsafe (e.g. inter-current illness, cardiovascular disease, cerebrovascular disease, severe diabetic retinopathy, nephropathy or neuropathy)
T1D patients who are currently on treatment with medications that alter heart rate (e.g. beta blockers)
T1D patients with closed or semi-closed loop insulin therapy

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table created by computer software (i.e. computerized sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
This is a randomized, cross-over design study where up to 20 men with T1D will be asked to complete two sessions to explore how reducing insulin versus eating carbohydrates compare for maintaining euglycemia and affecting performance around aerobic exercise. This study will initially only be undertaken in men to minimize any hormonal influences on glycaemic control.

Participants will be recruited through the Waikato Regional Diabetes Service (WRDS), and will initially be contacted by a member of the WRDS (letter, phone call, text or email) asking them if they are interested to participate. A participant information sheet will also be provided at this time.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
We expect this study to be adequately powered given smaller studies with less than 10 participants have shown significant differences in glucose levels. Repeated measures ANOVA’s will be performed using SPSS to compare time in normoglycaemia (primary outcome) and time in hyperglycaemia, capillary Ketone and lactate levels, and VO2 max (secondary outcomes). Chi-square tests will be performed to determine whether there are any differences in episodes of hypoglycaemia between the two groups. No analysis will be initiated prior to all data being collected and significance will be defined as a P value < 0.05.

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 outside Australia
Country [1] 21828 0
New Zealand
State/province [1] 21828 0
Waikato

Funding & Sponsors
Funding source category [1] 303674 0
University
Name [1] 303674 0
University of Waikato
Address [1] 303674 0
University of Waikato, Hillcrest, Hamilton, Waikato, New Zealand, 3216
Country [1] 303674 0
New Zealand
Primary sponsor type
University
Name
University of Waikato
Address
University of Waikato, Department of Health, Sport and Human Performance
Hillcrest, Hamilton, Waikato, New Zealand 3216
Country
New Zealand
Secondary sponsor category [1] 303779 0
None
Name [1] 303779 0
Address [1] 303779 0
Country [1] 303779 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304196 0
Health and disability ethics committees (HDEC)
Ethics committee address [1] 304196 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 304196 0
New Zealand
Date submitted for ethics approval [1] 304196 0
09/10/2019
Approval date [1] 304196 0
30/10/2019
Ethics approval number [1] 304196 0
19/NTB/175

Summary
Brief summary
Exercise is a cornerstone of management in type 1 diabetes (T1D) because of the improvement in glycemic control, reduction in cardiovascular disease and increased quality of life. However, the majority of patients with T1D do not meet their exercise requirements due to either the fear or risk of hypoglycaemia. To reduce these barriers, two consensus guidelines have been published that have contrasting approaches with either reducing the doses of insulin before exercise or eating additional carbohydrates. Importantly, these guidelines are predominantly based on expert opinion or laboratory-based studies of less than 10 participants. Furthermore, there are no published studies investigating which approach is more effective at controlling glucose levels around exercise, including whether there are any deleterious effects on performance from hyperglycaemia and/or ketonaemia and/or lactataemia. This study aims to answer these questions in a real-world setting, which will provide patients with T1D and their health professionals evidence-based advice for the best management of their diabetes around exercise.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96114 0
Dr Ryan Paul
Address 96114 0
Diabetes / Endocrinology, Waikato District Health Board Private Bag 3200, Pembroke St, Hamilton 3240
Country 96114 0
New Zealand
Phone 96114 0
+64 021 310974
Fax 96114 0
Email 96114 0
ryan.paul@waikatodhb.health.nz
Contact person for public queries
Name 96115 0
Mr Varun Ramesh Vartak
Address 96115 0
University of Waikato, Hillcrest, Hamilton, Waikato New Zealand 3216
Country 96115 0
New Zealand
Phone 96115 0
+64 022 5220014
Fax 96115 0
Email 96115 0
varun.r.vartak@gmail.com
Contact person for scientific queries
Name 96116 0
Dr Lynne Chepulis
Address 96116 0
University of Waikato, Research and Enterprise Department, Hillcrest, Hamilton, Waikato, New Zealand, 3216
Country 96116 0
New Zealand
Phone 96116 0
+64 022 6753353
Fax 96116 0
Email 96116 0
lynnec@waikato.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The data will not be made available as the study will be taking informed consent from every individual participant who will be a type 1 diabetes patient to not disclose or share any data, information with any other individual, organization without prior approval and thus, only post the approval of the individual participant, it would be possible to arrange for the data to be made available for sharing. Else it will not be shared with anyone.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary