ANZCTR - Registration

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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

15/09/2020

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]

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

Condition category

Condition code

Metabolic and Endocrine

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]

Treatment: Other

Comparator / control treatment

Control: Usual care
Participants will continue their usual daily activities.

Control group

Active

Outcomes

Primary outcome [1]

HbA1c (%, blood test)

Timepoint [1]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [1]

Fasting blood glucose (mmol/L, blood test)

Timepoint [1]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [2]

Fructosamine level (umol/L, blood test)

Timepoint [2]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [3]

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]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [4]

Glucose variability over 2 weeks of flash glucose monitoring (recordings are taken every 15 minutes) (standard deviation, measured using flash glucose monitoring)

Timepoint [4]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [5]

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]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [6]

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]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [7]

Daily insulin dose (average units/day over 7 days, participant diary)

Timepoint [7]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [8]

Insulin sensitivity (mg/kg/min, calculated using estimated glucose disposal rate)

Timepoint [8]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [9]

Blood pressure (mmHg, sphygmomanometer)

Timepoint [9]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [10]

Bodyweight (kg, scales)

Timepoint [10]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [11]

Waist circumference (cm, tape measure)

Timepoint [11]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [12]

Body fat percentage (%, DEXA body composition scan)

Timepoint [12]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [13]

Cardiorespiratory fitness (VO2peak, treadmill graded exercise test)

Timepoint [13]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [14]

Muscular strength (1-repetition maximum, Weight machine)

Timepoint [14]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [15]

Joint flexibility (cm, sit-and-reach test)

Timepoint [15]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [16]

Microalbuminuria (mg/mmol, urine albumin: creatinine ratio)

Timepoint [16]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [17]

Central arterial stiffness (Augmentation index, applanation tonometry)

Timepoint [17]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [18]

Liver function tests (ALT, AST blood test)

Timepoint [18]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [19]

NAFLD Fibrosis score (score calculator)

Timepoint [19]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [20]

Liver fat (% liver fat, MRI liver)

Timepoint [20]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [21]

Diabetic cardiomyopathy (systolic and diastolic function, Cardiac MRI)

Timepoint [21]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [22]

Cardiac autonomic neuropathy (Ewing score)

Timepoint [22]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [23]

Fear of hypoglycaemia (Hypoglycaemia Fear Survey -II)

Timepoint [23]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [24]

Quality of Life (Diabetes Quality of Life Measure)

Timepoint [24]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [25]

Liver fibrosis (kPa, Fibroscan)

Timepoint [25]

Baseline

Secondary outcome [26]

Brain natriuretic peptide (ng/L, blood test)

Timepoint [26]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [27]

Total testosterone level (nmol/L blood test)

Timepoint [27]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [28]

Total cholesterol level (mmol/L blood test)

Timepoint [28]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [29]

LDL cholesterol (mmol/L blood test)

Timepoint [29]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [30]

HDL cholesterol (mmol/L blood test)

Timepoint [30]

Baseline, and at 12 and 24 weeks after intervention commencement.

Secondary outcome [31]

Triglycerides (mmol/L blood test)

Timepoint [31]

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

Sex

Both males and females

Can healthy volunteers participate?

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

28/07/2017

Actual

28/07/2017

Date of last participant enrolment

Anticipated

Actual

19/03/2018

Date of last data collection

Anticipated

31/10/2018

Actual

12/10/2018

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Sydney

Address [1]

THE UNIVERSITY OF SYDNEY
Level 3W, Charles Perkins Centre D17
The University of Sydney
NSW 2006

Country [1]

Australia

Funding source category [2]

Charities/Societies/Foundations

Name [2]

Diabetes Australia Research Program

Address [2]

Diabetes Australia National Office
PO Box 3156
Canberra ACT 2601

Country [2]

Australia

Funding source category [3]

Commercial sector/Industry

Name [3]

Abbott Diabetes Care

Address [3]

1360 South Loop Rd Alameda, CA 94502

Country [3]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

SLHD Ethics Review Committee (RPAH Zone)

Ethics committee address [1]

Research Ethics and Governance Office (REGO)
RPAH Medical Centre
Suite 210A, 100 Carillon Avenue
NEWTOWN NSW 2042

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

22/02/2017

Approval date [1]

19/04/2017

Ethics approval number [1]

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

Prof Stephen Twigg

Address

THE UNIVERSITY OF SYDNEY
Level 3W, Charles Perkins Centre D17
The University of Sydney
NSW 2006

Country

Australia

Phone

+612 8627 1890

Fax

+612 8627 1604

[email protected]

Contact person for public queries

Name

Dr Angela Lee

Address

THE UNIVERSITY OF SYDNEY
Level 3W, Charles Perkins Centre D17
The University of Sydney
NSW 2006

Country

Australia

Phone

+61422875160

Fax

[email protected]

Contact person for scientific queries

Name

Prof Stephen Twigg

Address

THE UNIVERSITY OF SYDNEY
Level 3W, Charles Perkins Centre D17
The University of Sydney
NSW 2006

Country

Australia

Phone

+612 8627 1890

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Effect of High-Intensity Interval Training on Glyc... [More Details]
Plain language summary	No		Overall, there was no significant reduction in HbA... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Effect of high-intensity interval training on glycemic control in adults with type 1 diabetes and overweight or obesity: A randomized controlled trial with partial crossover.	2020	https://dx.doi.org/10.2337/dc20-0342

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically