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Trial registered on ANZCTR


Registration number
ACTRN12622000828729
Ethics application status
Approved
Date submitted
24/05/2022
Date registered
14/06/2022
Date last updated
29/05/2024
Date data sharing statement initially provided
14/06/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effect of dishabituation on hypoglycaemia awareness in patients with type 1 diabetes and impaired hypoglycaemia awareness.
Scientific title
Effect of exercise on hypoglycaemia awareness in individuals with type 1 diabetes and IAH under free-living conditions: A pilot study
Secondary ID [1] 307127 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes. 326293 0
Impaired awareness of hypoglycaemia 326597 0
Condition category
Condition code
Metabolic and Endocrine 323606 323606 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a pilot, single-centre, randomised, cross-over study in participants with both Type 1 diabetes and impaired awareness of hypoglycaemia (IAH) under free living conditions. Participants will be screened for IAH over the phone by our study doctor using the Clarke questionnaire. Once eligibility is confirmed, there will be a 2-week run in period where participants continue with their usual lifestyle. Participants will then be randomised into a 4-week period of either a tri-weekly low-intensity exercise or tri-weekly high-intensity exercise, with a 8-week wash-out in between the two exercise regimens after which, participants will be exposed to the alternative exercise programme for 4 weeks. A logbook will be provided to participants to enable them to record hypoglycaemia for 2 weeks. Logbooks will be used during the 2-week run in period and then in study weeks 5-7, 13-15 and 17-19. This will include a record of both autonomic and neuroglycopenic symptoms (Edinburg hypoglycaemia scale), with the severity of these symptoms being rated on a Likert scale from 1 to 7. (Appendix 6) All participants will be encouraged to record hypoglycaemia symptoms and glucose level in the logbook when at least one of the following conditions is met. a. Notification of urgent low alarm (3.1 mmol/l). b. Symptoms of hypoglycaemia as perceived by the participant c. Any time hypoglycaemia treatment (fast-acting carbohydrates) is instituted by the participant with glucose. Participants will be provided with an activity tracker watch (Garmin Forerunner 735xt) and Dexcom continuous glucose monitoring sensors if they do not have their own. Participants will be required to wear the Dexcom continuous glucose monitoring sensor for the whole study period. Participants will be given the option to wear the activity tracker for the whole study period or only when performing the exercise regimens.
Research staff will conduct a home visit to the participant's house to deliver and set up a cycle ergometer (MaXx KH-805 Programmable Upright Exercise Bike). Under the supervision of the research staff members, participants will perform a 10 second sprint test to determine their maximum power output generated (in Watts).
Low-intensity exercise for 4 weeks, 3 times a week. Participants will be required to cycle for 16 minutes at a low intensity corresponding to 15% of their peak power (measured during their peak power assessment at the familiarisation visit).
High-intensity exercise for 4 weeks, 3-times a week. After a 2-min warm up performed at an intensity equivalent to 15% peak power, participants will be required to engage in four 15-second maximal sprint efforts each separated by a 4-min period of light cycling at 15% peak power, finishing with 2-min of light cycling at 15% peak power.
Exercise to be performed at least 3 hours after the last insulin bolus and before the evening meal (dinner).
The primary outcome is the acceptability and feasibility of HIE as a home-based intervention. This outcome will be determined by the semi-structured interview at the end of the study. Weekly text messages and when needed, phone calls will be made to each participant to monitor adherence to the intervention.
Intervention code [1] 323582 0
Lifestyle
Intervention code [2] 323755 0
Treatment: Other
Comparator / control treatment
Each participant will act as their control as it is a cross over study and all participants will take part in both treatment groups.
Control group
Active

Outcomes
Primary outcome [1] 331376 0
The primary outcome is the acceptability of high intensity exercise as a home-based intervention. This outcome will be determined by the semi-structured interview at the end of the study
Timepoint [1] 331376 0
At the end of the 19 week study
Primary outcome [2] 331638 0
The feasibility of the high intensity exercise regimens as a home-based intervention determined by a semi-structured end of study interview.
Timepoint [2] 331638 0
At the end of the 19 week study
Secondary outcome [1] 409648 0
The feasibility of recruitment. The benchmarks for feasibility are:
60% of participants who meet the inclusion and exclusion criteria and accept the invitation to the study (feasibility of recruitment)
ii. 75% of participants who adhere to exercise schedule will be considered feasible (adherence to intervention)
Both of these benchmarks will be determined by an audit of study records and participant study data
Timepoint [1] 409648 0
At the end of the 19 week study
Secondary outcome [2] 409649 0
The adherence to the intervention using heart rate monitors for adherence
Timepoint [2] 409649 0
At the end of the 19 week study
Secondary outcome [3] 409650 0
The enjoyment of HIE through the semi-structured interview and Physical Activity Enjoyment Scale (PACES)
Timepoint [3] 409650 0
At the end of the 19 week study
Secondary outcome [4] 409651 0
Mean hypoglycaemia symptom score as measured by a validated questionnaire called the three factor model of hypogylycaemia (Deary IJ, et al. Diabetologia. 1993;36(8):771-7) during the last 2-week period of low-intensity and high-intensity exercise arms.
Timepoint [4] 409651 0
last 2-week period of low-intensity and high-intensity exercise arms.
Secondary outcome [5] 409652 0
Hypoglycaemia awareness score
Timepoint [5] 409652 0
At the end of the 19 week study
Secondary outcome [6] 409653 0
Percent time in hypoglycaemia (<3 mmol/l, <3.9 mmol/l), percent time in target range collected by the Dexcom continuous glucose monitoring sensor worn by each participant.
Timepoint [6] 409653 0
During the 19 week study period
Secondary outcome [7] 409654 0
Hypoglycaemia events (<3 mmol/l, <3.9 mmol/l) each lasting for at least 15 mins collected by the Dexcom continuous glucose monitoring sensor worn by each participant.
Timepoint [7] 409654 0
During the 19 week study period

Eligibility
Key inclusion criteria
Participant inclusion criteria.
1. Type 1 diabetes
2. Age 14 to 35 years
3. Impaired awareness of hypoglycaemia (Clarke score greater than or equal to 4 OR Gold Score greater than or equal to 4)
4. No clinical contraindication to exercise
5. HIE naïve or not participating in competitive team sports/sprints less than or equal to 1 /week
6. No expected participation in high intensity exercise other than the study-prescribed exercise for
the duration of the study
7. Willing to follow study instructions and attend visits
8. Willing to wear real-time CGM
9. Willing to wear a wrist-warn physical activity monitor (Garmin Forerunner)
10. Able to carry out exercise tasks
Minimum age
14 Years
Maximum age
35 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any clinical evidence of microvascular, macrovascular or neurological complications associated with T1D
2. Any clinical evidence of cardiovascular disease
3. Individuals not able to perform high-intensity exercise
4. Individuals with severe hypoglycaemia (coma, convulsion or requiring third-party assistance for treatment) in the last six months
5. Pregnancy or planned pregnancy within the study period
6. Another serious chronic illness or concomitant medication impacting one’s ability to perform the
exercise testing or study participation
7. Commenced new treatment (insulin pump or sensor) during or in the three months preceding the study

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomly assigned to arm order (control first, intervention first) using block randomisation with randomly differing block sizes of 2, 4, and 6. The website http://sealedenvelope.com will be used to generate the randomisation list. This list will be generated and held by a member of the study team playing no role in the recruitment of participants.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Free living study design
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Appropriate descriptive statistics (frequencies (%), mean (SD), median (IQR)) will be presented for all sociodemographic and clinical characteristics of the sample.
Mean and standard deviation, along with their 95% confidence interval, will be presented for continuous/interval outcome measures of interest (mean symptom score, Gold, Clarke, percent time in ranges) in each arm and for the paired difference between arms.
Where appropriate, linear mixed models will also be conducted to provide estimates of treatment effects accounting for the cross-over design. Models will include a random effect for individual and fixed effects for period and carryover. Evidence for a carryover effect will be explored though these linear mixed models and reported. Exploratory analysis examining the relationship between study week (within each arm and during washout) and individually collected symptom scores will also be conducted: scatterplots of symptom score by study week (in each period and during washout) will be produced and, if appropriate, a linear mixed model will be conducted to further explore.
To assist in determining the feasibility of the study design, the following will be presented to complement the information gathered through the semi-structured interviews:
The following proportions will be reported:
• proportion of participants that were invited and eligible who consented
• proportion of participants that adhered to intervention (at least three exercises per week at the appropriate intensity; no HIE in low-intensity exercise (LIE) arm)
o Split by arm
• Proportion withdrawn
The mean (SD), median (IQR) and range of the following will also be presented:
• Percent time CGM worn
• Percent time heart rate monitor worn
A qualitative analysis will be used to identify themes for semi-structured interview. Interviews will be transcribed and transcripts coded by independent researchers using inductive thematic analysis by Braun and Clark

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
18/03/2021
Date of last participant enrolment
Anticipated
Actual
25/03/2023
Date of last data collection
Anticipated
Actual
25/09/2023
Sample size
Target
12
Accrual to date
Final
7
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 22365 0
Perth Children's Hospital - Nedlands
Recruitment hospital [2] 22366 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [3] 22367 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 37529 0
6009 - Nedlands
Recruitment postcode(s) [2] 37530 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 311432 0
Charities/Societies/Foundations
Name [1] 311432 0
Diabetes Australia Research Program
Country [1] 311432 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Telethon Kids Institute
Address
Perth Children's Hospital 15 Hospital Avenue Nedlands 6009 WA
Country
Australia
Secondary sponsor category [1] 312827 0
None
Name [1] 312827 0
Address [1] 312827 0
Country [1] 312827 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310910 0
WA Department of Health Human Research Ethics Committee
Ethics committee address [1] 310910 0
Ethics committee country [1] 310910 0
Australia
Date submitted for ethics approval [1] 310910 0
17/03/2020
Approval date [1] 310910 0
31/08/2020
Ethics approval number [1] 310910 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 119310 0
Dr Mary Abraham
Address 119310 0
Telethon Kid's Institute Northern Entrance Perth Children's Hospital 15 Hospital Avenue Nedlands WA 6009
Country 119310 0
Australia
Phone 119310 0
+61 864565027
Fax 119310 0
Email 119310 0
Mary.abraham@health.wa.gov.au
Contact person for public queries
Name 119311 0
Mary Abraham
Address 119311 0
Telethon Kid's Institute Northern Entrance Perth Children's Hospital 15 Hospital Avenue Nedlands WA 6009
Country 119311 0
Australia
Phone 119311 0
+61 864565027
Fax 119311 0
Email 119311 0
Mary.abraham@health.wa.gov.au
Contact person for scientific queries
Name 119312 0
Mary Abraham
Address 119312 0
Telethon Kid's Institute Northern Entrance Perth Children's Hospital 15 Hospital Avenue Nedlands WA 6009
Country 119312 0
Australia
Phone 119312 0
+61 864565027
Fax 119312 0
Email 119312 0
Mary.abraham@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD data will not be shared. In the instance that this changes, amendments to ethics will be submitted. The individual participant data for this study will not be publically available


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.