Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000371493
Ethics application status
Approved
Date submitted
13/03/2016
Date registered
22/03/2016
Date last updated
10/05/2024
Date data sharing statement initially provided
10/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of high-intensity exercise training among people with early-onset type 2 diabetes mellitus
Scientific title
Effects of high-intensity exercise training among people with early-onset type 2 diabetes mellitus
Secondary ID [1] 288744 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
early-onset type 2 diabetes mellitus 297986 0
Condition category
Condition code
Metabolic and Endocrine 298140 298140 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
After baseline tests are performed, subjects will be randomised to either the exercise training group or the usual care (exercise advice) group.

Exercise training:
Subjects randomly allocated to the exercise training group will undertake supervised high-intensity exercise training three times per week for eight weeks. Training will be conducted on a stationary exercise bike, located at either RPA Hospital or a gym close to the subject's home – whichever is more convenient for them. The training physiotherapist or exercise physiologist will supervise each training session and will monitor heart rate and symptom scores.
As all sessions are supervised, attendance will be recorded throughout the training period.
Participants will wear a heart rate monitor, i.e. sensing strap on their chest, and a watch.
In the first week of training, after a 5-min warm-up, cycling at a low load, subjects will do six 30-s efforts on the bike at a heart rate that is about 80-90% of their maximum heart rate. For two minutes between each effort subjects will pedal at an easy load at 60-70% of maximum heart rate. At the end of the session they will pedal at a low load for a 5-minute cool down. The physiotherapist/exercise physiologist will increase the exercise periods to 60 s in the second week of training; and to two minutes for the final 6 weeks of exercise training. Recovery periods between exercise bouts will remain at two minutes. Each exercise training session will therefore only take between 25 to 35 minutes.
Intervention code [1] 294178 0
Treatment: Other
Comparator / control treatment
Usual care/Exercise advice
Usual care constitutes exercise advice. Subjects randomly allocated to the usual care/exercise advice group will be provided written advice about exercise (recommended type - aerobic, strength, combined - and dosage based on American Diabetes Association/American College of Sports Medicine guidelines) and reducing sedentary behaviour (modifying some daily habits). This advice will be discussed with the participant after randomisation allocation is revealed at the start of the intervention period of eight weeks.
After completion of the usual care participation, those randomised to usual care will be offered the high-intensity exercise training, which will be conducted exactly as described for those originally randomised to exercise training. Outcome measures collected after 8 weeks of exercise training will be the same as those conducted at 8 weeks.
Control group
Active

Outcomes
Primary outcome [1] 297649 0
Peak oxygen uptake measured using a standard cycle ergometry protocol with expired gas analysis and ventilation analysis using a standardised and calibrated metabolic cart system
Timepoint [1] 297649 0
1. Baseline (before randomization) 2. End of intervention period at 8 weeks.
Primary outcome [2] 297653 0
Glycaemic status (HbA1c; glycated haemoglobin) measured by high-performance liquid chromatography
Timepoint [2] 297653 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [1] 321690 0
Stroke volume at rest and during 50% pre-training upright max workload cycling in left-leaning supine position measured by echocardiography
Timepoint [1] 321690 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [2] 321739 0
Peak annulus velocity in early diastole (ventricular relaxation) at rest and during 50% pre-training upright max workload cycling in left-leaning supine position measured by echocardiography
Timepoint [2] 321739 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [3] 321740 0
Peripheral nerve function: Motor and sensory nerve excitability of median nerve using standard surface electromyography (EMG)
Timepoint [3] 321740 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [4] 321741 0
Endothelial Vasodilator Function measured by standardised EndoPAT Trademark protocol.
Timepoint [4] 321741 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [5] 321749 0
Expectations and experiences (including acceptability) of the aerobic interval training or usual care/exercise advice. These are qualitative outcomes that will be explored by semi-structured interview; and themes will be presented together in discussion..
Timepoint [5] 321749 0
1. End of intervention period at 8 weeks
Secondary outcome [6] 321750 0
Blood inflammatory markers (IL-6, TNF-alpha, CRP) measured by ELISA
Timepoint [6] 321750 0
At rest and during each of three submaximal exercise loads (20, 35, 50% of upright pre-training max workload) at:
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [7] 321751 0
Heat shock proteins (Hsp90, 72) by serum (Hsp90) or plasma (Hsp72) assay
Timepoint [7] 321751 0
At rest and during each of three submaximal exercise loads (20, 35, 50% of upright pre-training max workload) at:
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [8] 321752 0
Blood glucose measured by autoanalyzer
Timepoint [8] 321752 0
At rest and during each of three submaximal exercise loads (20, 35, 50% of upright pre-training max workload) at:
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [9] 321848 0
Brachial artery flow-mediated dilation (FMD) utilising standardised Doppler method
Timepoint [9] 321848 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [10] 321849 0
Lung volumes measured by body plethysmograph system.
Timepoint [10] 321849 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [11] 321850 0
Pulmonary blood flow measured by intra breath acetylene dilution
Timepoint [11] 321850 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [12] 321872 0
Barriers and motivators to exercise. These will be explored in an individual semi-structured interview.
Timepoint [12] 321872 0
1. End of intervention period at 8 weeks
Secondary outcome [13] 321874 0
Blood lactate measured by autoanalyzer
Timepoint [13] 321874 0
At rest and during each of three submaximal exercise loads (20, 35, 50% of upright pre-training max workload) at:
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [14] 321875 0
Arterialized venous blood pH and PCO2 measured by autoanalzyer
Timepoint [14] 321875 0
At rest and during each of three submaximal exercise loads (20, 35, 50% of upright pre-training max workload) at:
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [15] 321876 0
Free fatty acids measured by spectrophotometric method
Timepoint [15] 321876 0
At rest and during each of three submaximal exercise loads (20, 35, 50% of upright pre-training max workload) at:
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [16] 321877 0
Serum insulin measured by ELISA
Timepoint [16] 321877 0
At rest and during 50% upright pre-training max workload (submaximal) exercise at:
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [17] 321878 0
NT pro-BNP measured by ELISA
Timepoint [17] 321878 0
At rest and during 50% upright pre-training max workload (submaximal) exercise at:
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [18] 321879 0
Matrix metalloproteinases (MMP-2, -9) by zymography and MMP-1, -7 and tissue inhibitor TIMP-1 by ELISA
Timepoint [18] 321879 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [19] 321880 0
Monocyte number count isolated using a percoll gradient
Timepoint [19] 321880 0
At rest and during 50% upright pre-training max workload (submaximal) exercise at:
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [20] 321881 0
Questionnaire: SF12v2 with PIQ-6 measures pain severity and impact along with measures of functional health and well-being
Timepoint [20] 321881 0
1. Baseline (before randomization) 2. End of intervention period at 8 weeks
Secondary outcome [21] 321882 0
Questionnaire: Appraisal of diabetes scale
Timepoint [21] 321882 0
1. Baseline (before randomization) 2. End of intervention period at 8 weeks.
Secondary outcome [22] 321883 0
Questionnaire: Physical activity stages of change
Timepoint [22] 321883 0
1. Baseline (before randomization) 2. End of intervention period at 8 weeks.
Secondary outcome [23] 321884 0
Global Physical activity questionnaire (GPAQ)
Timepoint [23] 321884 0
1. Baseline (before randomization) 2. End of intervention period at 8 weeks.
Secondary outcome [24] 321885 0
Behavioural regulation in exercise questionnaire
Timepoint [24] 321885 0
1. Baseline (before randomization) 2. End of intervention period at 8 weeks.
Secondary outcome [25] 321886 0
Pittsburgh Sleep Quality Index questionnaire
Timepoint [25] 321886 0
1. Baseline (before randomization) 2. End of intervention period at 8 weeks.
Secondary outcome [26] 321887 0
Fatigue severity scale questionnaire and VAS fatigue
Timepoint [26] 321887 0
1. Baseline (before randomization) 2. End of intervention period at 8 weeks.
Secondary outcome [27] 321888 0
Questionnaire: Depression anxiety stress scale-21 (DASS21)
Timepoint [27] 321888 0
1. Baseline (before randomization) 2. End of intervention period at 8 weeks.
Secondary outcome [28] 321889 0
Questionnaire: Exercise benefits/barriers scale
Timepoint [28] 321889 0
1. Baseline (before randomization) 2. End of intervention period at 8 weeks.
Secondary outcome [29] 321890 0
Exercise self-efficacy questionnaire
Timepoint [29] 321890 0
1. Baseline (before randomization) 2. End of intervention period at 8 weeks.
Secondary outcome [30] 321891 0
Accelerometry to determine minutes per day of sedentary and moderate/vigorous intensity activity
Timepoint [30] 321891 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [31] 321892 0
Accelerometry to determine steps per day
Timepoint [31] 321892 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [32] 321893 0
Peripheral nerve function: H-reflex and M-wave of tibial nerve using the QTRAC system (semi-automated computerized system) and a multifunction data acquisition system.
Timepoint [32] 321893 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [33] 321894 0
monocyte cell surface marker expression and mitochondrial DNA concentration performed on RNA and DNA isolated from whole blood using the Qiagen whole blood DNA or RNA isolation kit
Timepoint [33] 321894 0
At rest and during 50% upright pre-training max workload (submaximal) exercise at:
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [34] 322031 0
Spirometry measured by body plethysmograph system.
Timepoint [34] 322031 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [35] 322032 0
Single breath diffusing capacity measured by body plethysmograph system.
Timepoint [35] 322032 0
1. Baseline (before randomization)
2. End of intervention period at 8 weeks
Secondary outcome [36] 349433 0
STOP-Bang questionnaire
Timepoint [36] 349433 0
Baseline only.

Eligibility
Key inclusion criteria
Diagnosis of T2D (two fasting plasma glucose values >7.0 mmol/l and/or a 2-hr value >11.1 mmol/l in an oral glucose tolerance test)
aged between 18 and 45 years
onset of T2D before age 40 yrs (i.e. early-onset)
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
chronic respiratory disease; current history of smoking; chest wall disease; heart failure; stroke; overt cardiovascular disease; and any other condition in which exercise is contraindicated, any condition precluding the ability to provide informed consent; pregnancy; and residence > 50 km from the hospital.

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)
A researcher blinded to allocation will open an opaque envelope (labelled with the study participant number) in front of the participant (after all pre-intervention testing is complete) and reveal the allocation. This researcher is a supervisor, i.e. not the PhD student (who will remain blinded to the allocation).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Another researcher generated the randomization sequence using a web-based program, put allocations in opaque envelopes, and sealed each envelope. The sealed envelopes are then stored on site at RPAH for access by the researcher revealing the allocation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Addition of a baseline comparison group who do not have diabetes. Twenty participants who do not have diabetes, and who are matched for age, gender and body mass index with the participants with diabetes, will be recruited. These participants without diabetes will undergo identical baseline testing to that undertaken by the participants with diabetes. They will not take part in the randomised controlled trial of high-intensity exercise training.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on the one previous study to report peak oxygen uptake (~23 ml/kg/min) in EOT2D; an hypothesized difference after exercise training between usual care exercise advice and the high-intensity exercise training group of 5 ml/kg/min and a within group standard deviation of 2.5 ml/kg/min in peak oxygen uptake; with 80% power at p<0.05, 5 subjects would be required per group. To account for possible drop-out with a novel high-intensity exercise training program we have increased group size to 10. We obtained ethical approval to recruit 12 to the exercise training group and 8 in the control group. Hence, 20 participants with EOT2D will be recruited for this study.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
28/03/2016
Actual
28/03/2016
Date of last participant enrolment
Anticipated
Actual
30/07/2022
Date of last data collection
Anticipated
Actual
18/10/2022
Sample size
Target
20
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5426 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 26526 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 12910 0
2050 - Camperdown
Recruitment postcode(s) [2] 42567 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 293097 0
Charities/Societies/Foundations
Name [1] 293097 0
Diabetes Australia Research Trust Grant
Country [1] 293097 0
Australia
Funding source category [2] 293109 0
Charities/Societies/Foundations
Name [2] 293109 0
Jill Nosworthy Bequest, Physiotherapy Research Foundation
Country [2] 293109 0
Australia
Primary sponsor type
Individual
Name
A/Prof Alison Harmer
Address
Discipline of Physiotherapy,
Faculty of Health Sciences,
The University of Sydney,
P.O. Box 170 Lidcombe, NSW 1825
Country
Australia
Secondary sponsor category [1] 291887 0
None
Name [1] 291887 0
n/a
Address [1] 291887 0
n/a
Country [1] 291887 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294601 0
Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 294601 0
Ethics committee country [1] 294601 0
Australia
Date submitted for ethics approval [1] 294601 0
Approval date [1] 294601 0
16/10/2015
Ethics approval number [1] 294601 0
X11-0060 & HREC/11/RPAH/72 updated 16/01/2018

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

Contacts
Principal investigator
Name 64322 0
Dr Alison Harmer
Address 64322 0
Discipline of Physiotherapy,
Faculty of Health Sciences,
The University of Sydney,
P.O. Box 170 Lidcombe, NSW 1825
Country 64322 0
Australia
Phone 64322 0
+61 2 9351 9706
Fax 64322 0
+61 2 9351 9278
Email 64322 0
[email protected]
Contact person for public queries
Name 64323 0
Alison Harmer
Address 64323 0
Discipline of Physiotherapy,
Faculty of Health Sciences,
The University of Sydney,
P.O. Box 170 Lidcombe, NSW 1825
Country 64323 0
Australia
Phone 64323 0
+61 2 9351 9706
Fax 64323 0
+61 2 9351 9278
Email 64323 0
[email protected]
Contact person for scientific queries
Name 64324 0
Alison Harmer
Address 64324 0
Discipline of Physiotherapy,
Faculty of Health Sciences,
The University of Sydney,
P.O. Box 170 Lidcombe, NSW 1825
Country 64324 0
Australia
Phone 64324 0
+61 2 9351 9706
Fax 64324 0
+61 2 9351 9278
Email 64324 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not all analyses will be completed as part of the PhD candidature and we do not have a definitive time for their analysis at this stage.


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.