Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001240336
Ethics application status
Approved
Date submitted
1/08/2017
Date registered
25/08/2017
Date last updated
16/07/2021
Date data sharing statement initially provided
16/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Brain blood flow, type 2 diabetes, and high-intensity interval training.
Scientific title
High-intensity interval training in type 2 diabetes. Does it improve brain blood flow, cognitive function and reduce the risk of cerebrovascular disease?
Secondary ID [1] 290798 0
Nil
Universal Trial Number (UTN)
U1111-1182-1377
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes 301444 0
Cerebrovascular Health 301445 0
Cognition 301446 0
Condition category
Condition code
Cardiovascular 301162 301162 0 0
Other cardiovascular diseases
Metabolic and Endocrine 301163 301163 0 0
Diabetes
Mental Health 303651 303651 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised to six months of high-intensity interval training will be compared to standard clinical management. For the first two months, the participants will be supervised by an exercise physiologist during exercise three times a week after which the participants will be encouraged to complete at least one session a week on their own (not compulsory). Cycling on a stationary ergometer will be completed during the supervised session at the School of Physical Education Sports and Exercise Science, University of Otago, Dunedin. If the participants decide to complete a session on their own, they will be free to undertake an exercise modality of their choice as long as they are following the high-intensity interval protocol which is provided as an attachment.
The sessions last for 20 – 30 min including a short warm up and cool down. The high-intensity interval training protocol is graduated targeting a heart rate of 90% of their age-predicted max (220 – age) see attached protocol which is attached to the ANZCTR registration form, interspaced lower intensity exercise which is participant self-selected.
The participant’s heart rates will be recorded for each session using individualised Polar Heart Rate monitors. The Polar Heart Rate monitors are given to the participants randomised to high-intensity interval training for the duration of the study. These recordings will be used to assess adherence and compliance to the training protocol. The participants will be contacted by study personnel at least on a weekly basis in the high-intensity interval group.
Intervention code [1] 296713 0
Lifestyle
Intervention code [2] 298836 0
Treatment: Other
Comparator / control treatment
In those who identify as having type 2 diabetes three months of standard clinical diabetes management as prescibed by their general practitioner will be the control comparator. These participants will be encouraged to remain in contacted with study personnel. Study personnel will contact them on a fortnightly basis.

Those participants without type 2 diabetes will not be randomised into the interventional groups. They will be compared to those with type 2 diabetes at baseline to assess the extent that diabetes affects brain blood flow, its reserve, and cognitive function.
Control group
Active

Outcomes
Primary outcome [1] 300575 0
Brain blood flow reserve assessed with postural change.

Brain blood flow will be measured using transcranial Doppler ultrasound insonating the middle cerebral artery.

The brain blood flow response to changes in posture which transiently alters arterial blood pressure will be assessed during repeated sit-to-stand tests for 5 minutes, each sit or stand phase will last 10 seconds.
Timepoint [1] 300575 0
Baseline for all participants and in those with type 2 diabetes post-intervention – Those randomised to high-intensity interval training will be reassessed at 6 months; Those randomised to standard clinical management will be reassessed at 3 months, and then will be offered to cross over to 6 months of high-intensity interval training then reassessed.
Primary outcome [2] 303022 0
Brain blood flow reserve assessed with alterations in arterial carbon dioxide.

Brain blood flow will be measured using transcranial Doppler ultrasound insonating the middle cerebral artery.

The brain blood flow response to changes in arterial carbon dioxide, giving an indication of chemical regulation of brain blood flow. This will be assessed i) during two stepped increases in arterial carbon dioxide of 5 mm Hg for 5 minutes, by controlled supplementation of 100% medical grade carbon dioxide into the inspired air. ii). during two stepped decreases in arterial carbon dioxide of 5 mm Hg for 5 minutes, by getting the participants to voluntarily hyperventilate (increase thier rate and depth of breathing).
Timepoint [2] 303022 0
Baseline for all participants and in those with type 2 diabetes post-intervention – Those randomised to high-intensity interval training will be reassessed at 6 months; Those randomised to standard clinical management will be reassessed at 3 months, and then will be offered to cross over to 6 months of high-intensity interval training then reassessed.
Secondary outcome [1] 330349 0
Cognitive function assessed in the executive domain using an automated computerised Stroop test.
Timepoint [1] 330349 0
Baseline for all participants and in those with type 2 diabetes post-intervention – Those randomised to high-intensity interval training will be reassessed at 6 months; Those randomised to standard clinical management will be reassessed at 3 months, and then will be offered to cross over to 6 months of high-intensity interval training then reassessed.
Secondary outcome [2] 337358 0
Cardiorespiratory capacity during an aerobic capacity test using an incremental protocol on a cycle ergometer.
Timepoint [2] 337358 0
Baseline for all participants and in those with type 2 diabetes post-intervention – Those randomised to high-intensity interval training will be reassessed at 6 months; Those randomised to standard clinical management will be reassessed at 3 months, and then will be offered to cross over to 6 months of high-intensity interval training then reassessed.
Secondary outcome [3] 337504 0
Venipuncture for glycosylated haemoglobin.
Timepoint [3] 337504 0
Baseline for all participants and in those with type 2 diabetes post-intervention – Those randomised to high-intensity interval training will be reassessed at 6 months; Those randomised to standard clinical management will be reassessed at 3 months, and then will be offered to cross over to 6 months of high-intensity interval training then reassessed.
Secondary outcome [4] 337505 0
Venipuncture for plasma lipid profiles.
Timepoint [4] 337505 0
Baseline for all participants and in those with type 2 diabetes post-intervention – Those randomised to high-intensity interval training will be reassessed at 6 months; Those randomised to standard clinical management will be reassessed at 3 months, and then will be offered to cross over to 6 months of high-intensity interval training then reassessed.
Secondary outcome [5] 337506 0
Blood volume will be measured using carbon monoxide dilution rebreathing.
Timepoint [5] 337506 0
Baseline for all participants and in those with type 2 diabetes post-intervention – Those randomised to high-intensity interval training will be reassessed at 6 months; Those randomised to standard clinical management will be reassessed at 3 months, and then will be offered to cross over to 6 months of high-intensity interval training then reassessed.
Secondary outcome [6] 337720 0
Venipuncture for fasting glucose.
Timepoint [6] 337720 0
Baseline for all participants and in those with type 2 diabetes post-intervention – Those randomised to high-intensity interval training will be reassessed at 6 months; Those randomised to standard clinical management will be reassessed at 3 months, and then will be offered to cross over to 6 months of high-intensity interval training then reassessed.
Secondary outcome [7] 337721 0
Venipuncture for fasting insulin.
Timepoint [7] 337721 0
Baseline for all participants and in those with type 2 diabetes post-intervention – Those randomised to high-intensity interval training will be reassessed at 6 months; Those randomised to standard clinical management will be reassessed at 3 months, and then will be offered to cross over to 6 months of high-intensity interval training then reassessed.

Eligibility
Key inclusion criteria
For those who identify as having type 2 diabetes.
Confirmed diagnosis of Type 2 diabetes
Aged between 40 - 65 years
Able to give informed consent

For those who identify as healthy volunteers.
Aged between 40 - 65 years
Able to give informed consent
Minimum age
40 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
For those who identify as having type 2 diabetes.
Unable to give informed consent
Any pre-existing cardiovascular and cerebrovascular disease and peripheral neuropathy
Currently treated with beta-blocker or rate control therapy

For those who identify as healthy volunteers.
Found to have undiagnosed type 2 diabetes.
Unable to give informed consent
Any pre-existing cardiovascular and cerebrovascular disease and peripheral neuropathy
Currently treated with beta-blocker or rate control therapy

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis
Based on estimates from Petrica, et al 2007 (Wein Klin Wochenschr 119(11-12): p 365-71) where brain blood flow reserve was reduced by 6.6 ± 1.5 cm.s-1 in people with diabetes than those without. We anticipate 10 participants per group to detect a difference of a one-third between the non-diabetic controls and the participants with diabetes, and improvement in brain blood flow reserve with the training of one-third (90% power, P <0.05). Allowing for loss to attrition we will recruit 15 participants per diabetic group (total of 30).

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/11/2017
Actual
Date of last participant enrolment
Anticipated
21/06/2018
Actual
Date of last data collection
Anticipated
21/12/2018
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment outside Australia
Country [1] 8523 0
New Zealand
State/province [1] 8523 0
Otago

Funding & Sponsors
Funding source category [1] 295220 0
Government body
Name [1] 295220 0
Lottery Health Research
Country [1] 295220 0
New Zealand
Funding source category [2] 295221 0
Charities/Societies/Foundations
Name [2] 295221 0
Healthcare Otago Charitable Trust
Country [2] 295221 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
University of Otago
PO Box 56
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 296117 0
None
Name [1] 296117 0
Address [1] 296117 0
Country [1] 296117 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298284 0
Northern B Health and Disability Ethics Comittee
Ethics committee address [1] 298284 0
C/- Ministry of Health
PO Box 5013
Wellington 6145
Ethics committee country [1] 298284 0
New Zealand
Date submitted for ethics approval [1] 298284 0
19/07/2017
Approval date [1] 298284 0
22/09/2017
Ethics approval number [1] 298284 0
17/NTB/145

Summary
Brief summary
People with type 2 diabetes require a disproportionate amount of New Zealand’s medical resources. These patients are twice as likely to have cardiovascular and cerebrovascular disease as non-diabetics. In fact, 65% of cardiovascular and cerebrovascular disease admissions are people with type 2 diabetes, and account for ~30% of inpatient hospitalisation cost, which is predicted to increase in the future. Therefore, prevention of diabetic cerebrovascular disease is important for directing the development of preventative strategies to mitigate the social and economic burden for New Zealand.
Stroke the most severe outcome of cerebrovascular disease causes prolonged morbidity and consumes ~$50,000 per case. We know that people with diabetes are twice as likely to suffer from a stroke, which may be caused by alterations in brain blood flow or its reserve that appears to occur in people with diabetes. These changes elevate the risk of cerebrovascular disease including stroke in other populations. In addition, there is indirect evidence that brain blood flow is perturbed with diabetes, with multiple studies showing cognitive function is more commonly impaired. Impaired cognitive function is associated with reduced and/or abnormal brain blood flow in other populations.
Three months of exercise training in healthy but previously sedentary people improves cognitive function, brain blood flow and its reserve. However the effect of exercise on brain blood flow has not been tested in people with diabetes. The clinical high-intensity exercise programme our laboratory uses, may offer a simple tool to improve brain blood flow, cognitive function and reduce the risk of cerebrovascular disease in people suffering from type 2 diabetes. Our research group has recently used HIT to improve daily blood glucose in a small group of pre-diabetic participants. High-intensity interval training interspaces bursts of intense exercise reaching 90% of individual maximum heart rates with periods of exercise at lower intensities. Importantly, HIT improves blood glucose and fitness more than traditional exercise recommendations, and seems to be more popular. We now propose to enrol diagnosed diabetic patients in a six month HIT program to test the hypothesis that this popular exercise method can improve brain blood flow, cognitive function and reduce cerebrovascular disease risk.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1959 1959 0 0
/AnzctrAttachments/372064-HIT protocol.pdf (Protocol)

Contacts
Principal investigator
Name 71314 0
Dr Luke Wilson
Address 71314 0
Department of Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 71314 0
New Zealand
Phone 71314 0
+64274491401
Fax 71314 0
Email 71314 0
[email protected]
Contact person for public queries
Name 71315 0
Dr Luke Wilson
Address 71315 0
Department of Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 71315 0
New Zealand
Phone 71315 0
+64274491401
Fax 71315 0
Email 71315 0
[email protected]
Contact person for scientific queries
Name 71316 0
Dr Luke Wilson
Address 71316 0
Department of Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 71316 0
New Zealand
Phone 71316 0
+64274491401
Fax 71316 0
Email 71316 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


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.