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Trial registered on ANZCTR


Registration number
ACTRN12617000478314
Ethics application status
Approved
Date submitted
28/03/2017
Date registered
3/04/2017
Date last updated
6/06/2019
Date data sharing statement initially provided
6/06/2019
Date results information initially provided
6/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of high-intensity interval training on glycaemic control in adults with type 1 diabetes
Scientific title
Effects of high-intensity interval training on glycaemic control in adults with type 1 diabetes
Secondary ID [1] 291550 0
None
Universal Trial Number (UTN)
U1111-1194-7465
Trial acronym
HIIT T1D
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 302641 0
Condition category
Condition code
Metabolic and Endocrine 302158 302158 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised controlled trial (12 weeks) with subsequent partial cross-over (12 weeks)

Baseline study period and randomisation (Weeks 1-2):
Study participants will have initial baseline cardiorespiratory fitness assessment in a graded exercise test on treadmill with breath-by-breath gas analysis to determine individual peak heart rate and VO2peak in the Royal Prince Alfred Charles Perkins Centre clinic and gym. Participants will have a baseline HbA1c and a 2-week continuous glucose recording with FreeStyle Libre Pro flash glucose monitor.

Participants will then be randomised to either intervention or control groups.

Study Period 1: “Randomised controlled trial” (Weeks 3-14):
Intervention group: High-intensity interval training
Participants will undertake 3 sessions/week of high-intensity interval training (HIIT) exercise for 12 weeks: consisting of 2 sessions/week on a cycle ergometer or treadmill in the Royal Prince Alfred Charles Perkins Centre gym supervised by a study investigator (Endocrinologist and/or Accredited Exercise Physiologist), and 1 session/week unsupervised walking/jogging at home.

The HIIT exercise session will last 33 minutes consisting of: 5 minutes of warm-up at approximately 60% peak heart rate, then 4 bouts of 4-minute high-intensity intervals at 85-95% peak heart rate interspersed with 3 bouts of 3-minute recovery intervals at 50-70% peak heart rate, and concluding with 3 minutes of cool-down at approximately 50% peak heart rate. Participants will have their exercise individually progressed over the initial 2 weeks (by the supervising Endocrinologist/Exercise Physiologist) so that they are able to complete the full HIIT exercise session by week 3.

Measurement of exercise intensity: A polar heart rate monitor (heart rate sensor soft chest strap + watch) will be used for all exercise sessions to achieve the required target exercise intensity.

Control group: Participants will continue their usual daily activities and diet.


Study Period 2: “Partial Cross Over” (Weeks 15-26):
Intervention group: Participants will continue 3 sessions/week of HIIT exercise (33minutes/session) unsupervised at home for 12 weeks.
Control group: Participants will undertake 3 sessions/week of high-intensity interval training (HIIT) exercise for 12 weeks: consisting of 2 sessions/week on a cycle ergometer or treadmill in the Royal Prince Alfred Charles Perkins Centre gym supervised by a study investigator (Endocrinologist and/or Accredited Exercise Physiologist), and 1 session/week unsupervised walking/jogging at home, as described for the week 1-12 exercise program in the original intervention group.

Insulin dose adjustment: All participants in the intervention and control groups will have once-weekly review of their home blood glucose monitoring results by the study Endocrinologist (in person, on phone, or via email as per participant preference) for advice on individualised insulin dose adjustment during Study Period 1 and Study Period 2.

Adherence: For the participants participating in the HIIT exercise intervention, attendance will be recorded in an attendance record logbook at the gym, and reported as a percentage of total gym exercise sessions performed. At the weekly review, participants will be asked about their performance of home HIIT exercise, and this will be reported as a percentage of home exercise sessions performed.
Intervention code [1] 297616 0
Treatment: Other
Comparator / control treatment
Control: Usual care
Participants will continue their usual daily activities.
Control group
Active

Outcomes
Primary outcome [1] 301588 0
HbA1c (%, blood test)
Timepoint [1] 301588 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [1] 333195 0
Fasting blood glucose (mmol/L, blood test)
Timepoint [1] 333195 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [2] 333196 0
Fructosamine level (umol/L, blood test)
Timepoint [2] 333196 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [3] 333197 0
Mean glucose level over 2 weeks of flash glucose monitoring (recordings are taken every 15 minutes) (mmol/L, measured using flash glucose monitoring)
Timepoint [3] 333197 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [4] 333198 0
Glucose variability over 2 weeks of flash glucose monitoring (recordings are taken every 15 minutes) (standard deviation, measured using flash glucose monitoring)
Timepoint [4] 333198 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [5] 333199 0
Hypoglycaemia duration over 2 weeks of flash glucose monitoring (recordings are taken every 15 minutes) (total minutes/day, measured using flash glucose monitoring)
Timepoint [5] 333199 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [6] 333200 0
Hyperglycaemia duration over 2 weeks of flash glucose monitoring (recordings are taken every 15 minutes) (total minutes/day, measured using flash glucose monitoring)
Timepoint [6] 333200 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [7] 333201 0
Daily insulin dose (average units/day over 7 days, participant diary)
Timepoint [7] 333201 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [8] 333202 0
Insulin sensitivity (mg/kg/min, calculated using estimated glucose disposal rate)
Timepoint [8] 333202 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [9] 333203 0
Blood pressure (mmHg, sphygmomanometer)
Timepoint [9] 333203 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [10] 333204 0
Bodyweight (kg, scales)
Timepoint [10] 333204 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [11] 333205 0
Waist circumference (cm, tape measure)
Timepoint [11] 333205 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [12] 333206 0
Body fat percentage (%, DEXA body composition scan)
Timepoint [12] 333206 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [13] 333207 0
Cardiorespiratory fitness (VO2peak, treadmill graded exercise test)
Timepoint [13] 333207 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [14] 333208 0
Muscular strength (1-repetition maximum, Weight machine)
Timepoint [14] 333208 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [15] 333209 0
Joint flexibility (cm, sit-and-reach test)
Timepoint [15] 333209 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [16] 333210 0
Microalbuminuria (mg/mmol, urine albumin: creatinine ratio)
Timepoint [16] 333210 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [17] 333212 0
Central arterial stiffness (Augmentation index, applanation tonometry)
Timepoint [17] 333212 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [18] 333213 0
Liver function tests (ALT, AST blood test)
Timepoint [18] 333213 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [19] 333214 0
NAFLD Fibrosis score (score calculator)
Timepoint [19] 333214 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [20] 333215 0
Liver fat (% liver fat, MRI liver)
Timepoint [20] 333215 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [21] 333216 0
Diabetic cardiomyopathy (systolic and diastolic function, Cardiac MRI)
Timepoint [21] 333216 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [22] 333217 0
Cardiac autonomic neuropathy (Ewing score)
Timepoint [22] 333217 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [23] 333218 0
Fear of hypoglycaemia (Hypoglycaemia Fear Survey -II)
Timepoint [23] 333218 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [24] 333219 0
Quality of Life (Diabetes Quality of Life Measure)
Timepoint [24] 333219 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [25] 333224 0
Liver fibrosis (kPa, Fibroscan)
Timepoint [25] 333224 0
Baseline
Secondary outcome [26] 333227 0
Brain natriuretic peptide (ng/L, blood test)
Timepoint [26] 333227 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [27] 333228 0
Total testosterone level (nmol/L blood test)
Timepoint [27] 333228 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [28] 333371 0
Total cholesterol level (mmol/L blood test)
Timepoint [28] 333371 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [29] 333372 0
LDL cholesterol (mmol/L blood test)
Timepoint [29] 333372 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [30] 333373 0
HDL cholesterol (mmol/L blood test)
Timepoint [30] 333373 0
Baseline, and at 12 and 24 weeks after intervention commencement.
Secondary outcome [31] 333374 0
Triglycerides (mmol/L blood test)
Timepoint [31] 333374 0
Baseline, and at 12 and 24 weeks after intervention commencement.

Eligibility
Key inclusion criteria
Inclusion criteria:
a. Age 18-70 years,
b. Type 1 diabetes greater than or equal to 1 year duration,
c. HbA1c 7.5-10.5%,
d. BMI greater than or equal to 25 kg/m^2,
e. Self-manage diabetes with multiple-daily insulin injections or subcutaneous insulin pump, with flexible dosing according to carbohydrate counting and self-monitored blood glucose testing,
f. Exercising less than 150minutes/week moderate-intensity exercise for the past 6 months.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:
a. Conditions which prevent exercise participation (such as arthritis, unstable cardiac condition, active foot ulcer, untreated severe retinopathy),
b. Unable to have an MRI scan due to immovable implanted metal in the body (eg. Cardiac pacemaker/defibrillator, eye or ear implants, shrapnel), or severe claustrophobia.
c. Pregnancy or breastfeeding.

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)
Participants will then be randomised to either intervention or control groups. Randomisation will be by computer-generated randomisation sequence, with the allocation sequence contained in sequentially-numbered sealed opaque envelopes
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Randomised controlled trial (Study Period 1: initial 12 weeks) with partial cross-over (Study Period 2: subsequent 12 weeks).
Participants in the intervention group will undertake 12 weeks of supervised HIIT exercise in Study Period 1, and then 12 weeks of unsupervised HIIT exercise in Study Period 2.
Participants in the control group will have 12 weeks of usual care in Study Period 1, and then 12 weeks of supervised HIIT exercise in Study Period 2.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size calculation is based on a predicted mean HbA1c reduction of 0.7% by the exercise intervention from a baseline group mean (+/-SD) HbA1c of 9.0% +/- 0.6%, with a=0.05 and power 80% for a 2-sided test. The calculated sample size group is thus 12 per group. After allowing for 20% drop-out, the planned sample size is 15 per group, total of 30 participants. The predicted HbA1c decrease is based on a meta-analysis of exercise training in people with type 2 diabetes showing that exercise was associated with an overall reduction in HbA1c of 0.67%, and structured exercise of 150minutes per week or more was associated with an absolute HbA1c reduction of 0.89%.

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)
NSW

Funding & Sponsors
Funding source category [1] 296038 0
University
Name [1] 296038 0
University of Sydney
Address [1] 296038 0
THE UNIVERSITY OF SYDNEY
Level 3W, Charles Perkins Centre D17
The University of Sydney
NSW 2006
Country [1] 296038 0
Australia
Funding source category [2] 296044 0
Charities/Societies/Foundations
Name [2] 296044 0
Diabetes Australia Research Program
Address [2] 296044 0
Diabetes Australia National Office
PO Box 3156
Canberra ACT 2601
Country [2] 296044 0
Australia
Funding source category [3] 297119 0
Commercial sector/Industry
Name [3] 297119 0
Abbott Diabetes Care
Address [3] 297119 0
1360 South Loop Rd Alameda, CA 94502
Country [3] 297119 0
United States of America
Primary sponsor type
Government body
Name
Sydney Local Health District
Address
Sydney Local Health District
Level 11, KGV Building
Missenden Road
CAMPERDOWN NSW 2050
Country
Australia
Secondary sponsor category [1] 296132 0
None
Name [1] 296132 0
Address [1] 296132 0
Country [1] 296132 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297297 0
SLHD Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 297297 0
Research Ethics and Governance Office (REGO)
RPAH Medical Centre
Suite 210A, 100 Carillon Avenue
NEWTOWN NSW 2042
Ethics committee country [1] 297297 0
Australia
Date submitted for ethics approval [1] 297297 0
22/02/2017
Approval date [1] 297297 0
19/04/2017
Ethics approval number [1] 297297 0
X17-0055 & HREC/17/RPAH/74

Summary
Brief summary
Background
Blood glucose control is fundamental to the management of type 1 diabetes (T1D) to reduce rates of diabetes complications. Exercise studies have not been able to show a consistent benefit on blood glucose control in people with T1D. High-intensity interval training has been found to improve long term blood glucose control (HbA1c level) in people with type 2 diabetes. To our knowledge, there are no adequately-powered studies looking at the effect of HIIT exercise on HbA1c in people with T1D.

Research Question
In adults with type 1 diabetes who are overweight or obese, will 12-weeks of high-intensity interval training improve blood glucose control (HbA1c), cardiovascular risk factors and diabetes complications?

Study aim
This study will potentially show the first evidence that HIIT exercise can improve HbA1c without excess risk of hypoglycaemia (low glucose) in adults with T1D. Also, such exercise intervention may improve cardiovascular risk factors, and some aspects of traditional and novel diabetes complications including measures of non-alcoholic fatty liver disease, diabetic cardiomyopathy and cardiac autonomic neuropathy.

Research design and methods
In a randomised controlled trial (study period 1; 12 weeks) with subsequent partial cross-over (study period 2; 12 weeks), 30 sedentary adults with T1D who are overweight or obese will be randomised to the intervention group (12 weeks of supervised high-intensity interval training (HIIT) exercise, and then 12 weeks of unsupervised exercise) or the control group (12 weeks of usual care, and then 12 weeks of supervised HIIT exercise). The primary outcome will be HbA1c blood test at the end of the randomised controlled trial period (12 weeks exercise vs usual care), with a secondary outcome being to compare HbA1c with all 30 participants’ own baseline. The partial cross-over design allows all participants to benefit from undertaking the supervised HIIT, and has the advantage of increasing statistical power to secondary outcome measures.

Further secondary outcomes include measurement of hypoglycaemia, hyperglycaemia and glucose variability using a glucose sensor, cardiorespiratory fitness using a treadmill fitness test, and cardiovascular risk factors such as blood pressure, cholesterol levels, weight, and body composition with a DEXA scan. Several diabetic complications will be examined for improvements after exercise, including diabetic cardiomyopathy and non-alcoholic fatty liver disease with cardiac and liver MRI, and cardiac autonomic neuropathy with bedside electrocardiography (ECG) testing. Importantly, changes in quality of life and fear of hypoglycaemia will be measured with validated diabetes-specific questionnaires.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73622 0
Prof Stephen Twigg
Address 73622 0
THE UNIVERSITY OF SYDNEY
Level 3W, Charles Perkins Centre D17
The University of Sydney
NSW 2006
Country 73622 0
Australia
Phone 73622 0
+612 8627 1890
Fax 73622 0
+612 8627 1604
Email 73622 0
stephen.twigg@sydney.edu.au
Contact person for public queries
Name 73623 0
Dr Angela Lee
Address 73623 0
THE UNIVERSITY OF SYDNEY
Level 3W, Charles Perkins Centre D17
The University of Sydney
NSW 2006
Country 73623 0
Australia
Phone 73623 0
+61422875160
Fax 73623 0
Email 73623 0
alee8473@uni.sydney.edu.au
Contact person for scientific queries
Name 73624 0
Prof Stephen Twigg
Address 73624 0
THE UNIVERSITY OF SYDNEY
Level 3W, Charles Perkins Centre D17
The University of Sydney
NSW 2006
Country 73624 0
Australia
Phone 73624 0
+612 8627 1890
Fax 73624 0
Email 73624 0
stephen.twigg@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data sharing is not included in our study protocol approved by ethics committee.
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Ethical approval
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?
No
Results – basic reporting
Results – plain English summary