Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000988156
Ethics application status
Approved
Date submitted
27/06/2019
Date registered
11/07/2019
Date last updated
29/06/2021
Date data sharing statement initially provided
11/07/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Improving brain health in at risk populations with aerobic exercise
Scientific title
Aerobic exercise to improve cerebrovascular function, mood and cognition in middle-aged and older physically inactive overweight/obese adults
Secondary ID [1] 298603 0
None
Universal Trial Number (UTN)
U1111-1236-0016
Trial acronym
ACE Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cognitive impairment 313454 0
Dementia 313538 0
Condition category
Condition code
Neurological 311887 311887 0 0
Dementias
Physical Medicine / Rehabilitation 311968 311968 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Aerobic exercise
The objective of this research is to investigate the effects of regular aerobic exercise on cerebrovascular function, mood and cognition in middle-aged to older adults. A randomised control trial that aims to determine whether a high or low level of aerobic exercise training for 16 weeks can improve cerebrovascular function, mood and cognition in a physically inactive, middle-aged to older, overweight and obese cohort who are at risk of cognitive decline and dementia. It is hypothesised that both the higher levels of exercise training will improve cognition and mood in this cohort by improving cerebrovascular function, as well as improving cardiovascular function and general physiological and psychological markers of health. However, it is unknown if less aerobic exercise training will elicit any changes in cognition and mood by improving cerebrovascular function. Hence, the aim here is to determine the optimal amount of aerobic exercise training to improve the aforementioned outcomes.
We will aim to recruit one hundred and thirty-five participants for this study. Recruitment will occur via an approved media release that incorporates physical advertisement, social media and information on the USQ website. The individuals will be recruited from community organisations in and around Ipswich, Toowoomba and Brisbane. Respondents will initially be screened for suitability using the Exercise and Sports Science Australia (ESSA) Adult Pre-exercise Screening System, the Yale Physical Activity Survey and a medical history questionnaire to determine whether participants meet the inclusion and/or exclusion criteria.
Once participants are recruited, voluntary written informed consent will be obtained prior to any assessment being performed and their allocation to one of the two arms of the study at a 2 is to 1 ratio (intervention:control). Further, participants will be asked to complete a nutritional questionnaire at 0 and 16 weeks, so that this can be assessed and that any effects that are noted throughout the study are due to the exercise intervention and not due to changes in nutritional behaviour.
The two arms of this study will consist of a wait-list (control group), which will not participate in any exercise training, and a second arm (the exercise group) that will participate in 2 – 4 aerobic exercise sessions per week. Participants that are allocated to the exercise arm will participate in aerobic exercise training for either two, three or four days per week for 16 weeks (i.e., the participant can choose how many sessions they attend). These sessions will be conducted as supervised group sessions run by student exercise physiologists in the presence of an accredited Clinical Exercise Physiologist at the University of Southern Queensland Ipswich Campus.
Participants in the second arm or exercise arm of the study can attend any of these sessions, as long as they participate in a minimum of two sessions per week. All sessions will last for 40 min, incorporating both a 5-min gentle warm-up and cool-down. The body of the sessions will be performed at a moderate intensity (Borg RPE 5-6), vigorous-high intensity (Borg RPE 7-8) or a mix of the two. Participants will be requested to perform these exercise sessions at a higher intensity every four weeks from the previous four weeks (this will be based on the Borg rating of perceived exertion (CR-10) scale). These sessions will incorporate steady-state aerobic exercise (i.e. walking), circuit training or a mix of the two types of training.
Once informed about the study and its requirements, by providing potential participants with a participant information sheet, participants that meet part of the inclusion criteria will attend USQ Ipswich for baseline screening and testing. Prior to the start of any testing during visit 1, informed consent will be first voluntarily obtained and, once acknowledged, testing and screening will commence. These visits will incorporate the following methods:
• Cerebrovascular responsiveness to hypercapnia and cognitive stimuli (NIH Toolbox, Trail Making Task) using transcranial Doppler sonography;
• Profile of Mood States to ascertain current mood;
• Anthropometry, determined by body weight and height (body mass index calculation), waist and hip circumferences (waist to hip ratio calculation) and Dual-energy X-ray absorptiometry (DEXA) which will ascertain body composition of total fat mass, lean mass, body fat percentage, and bone mineral content and density;
• Systolic and diastolic blood pressure and arterial elasticity will be measured non-invasively using a Research Cardiovascular Profiling System;
• Biomarker analyses after blood is collected; and
• Exercise capacity will be assessed using a 6 minute walk test at 0 and 16 weeks and handgrip strength will be determined using hand dynamometry.
Intervention code [1] 314862 0
Lifestyle
Intervention code [2] 314911 0
Treatment: Other
Comparator / control treatment
The first arm of the study will be the wait-list (control) group, which will not participate in any exercise training, Once the study has concluded, the control group will be provided with the exercise regime used in this study so that they can utilise this resource in their day-to-day lives. They will be provided with this 16 weeks after their initial enrolment.
Control group
Active

Outcomes
Primary outcome [1] 320555 0
Cerebrovascular responsiveness to hypercapnia using a transcranial Dopper sonography
Timepoint [1] 320555 0
Pre-intervention and 16 weeks after intervention commencement
Primary outcome [2] 320556 0
Cerebrovascular responsiveness to cognitive stimuli using the NIH Toolbox, Corsi-block sorting test and the trail making task (parts A and B).
Timepoint [2] 320556 0
Pre-intervention and 16 weeks after intervention commencement
Secondary outcome [1] 371992 0
Mean cognitive tests scores using NIH Toolbox battery, Trail Making Task (Parts A & B) and Corsi-block sorting test. This is a composite secondary outcome.
Timepoint [1] 371992 0
Pre-intervention and 16 weeks after intervention commencement
Secondary outcome [2] 371993 0
Mean profile of mood states score
Timepoint [2] 371993 0
Pre-intervention and 16 weeks after intervention commencement
Secondary outcome [3] 371994 0
Cardiovascular profile (arterial stiffness and blood pressure) using a non-invasive HDI/Pulsewave™ CR-2000 Research Cardiovascular Profiling System. This is a composite secondary outcome..
Timepoint [3] 371994 0
Pre-intervention and 16 weeks after intervention commencement
Secondary outcome [4] 371995 0
Metabolic, inflammatory, haematological and general biochemical markers (serum and plasma). These are exploratory outcomes. This is a composite secondary outcome.
Timepoint [4] 371995 0
Pre-intervention and 16 weeks after intervention commencement
Secondary outcome [5] 371996 0
Changes in 6 minute walk test
Timepoint [5] 371996 0
Pre-intervention and 16 weeks after intervention commencement
Secondary outcome [6] 371997 0
Changes in handgrip strength test using a digital dynamometer.
Timepoint [6] 371997 0
Pre-intervention and 16 weeks after intervention commencement
Secondary outcome [7] 371998 0
Changes in body composition using a Dual-energy X-ray absorptiometry (DEXA) (Luna Corp Prodigy Advancer Model GE). Total fat mass, lean mass, body fat percentage, and bone mineral content and density will be assessed.
Timepoint [7] 371998 0
Pre-intervention and 16 weeks after intervention commencement

Eligibility
Key inclusion criteria
Be aged 50-80 years
Be physically inactive
Have a body mass index >25 kg/m2 (we will calculate this)
Have blood pressure below 160/100mmHg (we will determine this at the screening visit)
Have an adequate ultrasound signal (we will determine this at the screening visit).
Not have heart, kidney or liver disease (excluding fatty liver disease), cancer or a neurological disorder (e.g. stroke)
Not taking insulin, anticoagulants or hormone replacement therapy
Minimum age
50 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Cognitive impairment and/or dementia
Less than 150 minutes of moderate to vigorous intensity exercise/week
BMI greater than 25 kg/m2
resting blood pressure equal to or less than 160/100mmHg
Chronic kidney disease
Chronic liver disease (excluding fatty liver disease)
Coronary heart disease
Congestive heart failure
Atrial fibrillation
Prior myocardial infarction
Carcinoma (unless in remission or similar)
Stroke
Aneurysm
Epilepsy
Multiple sclerosis
Parkinson’s disease
Neuropathies
Presence of a fistulae
Smoker
Prescribed insulin, hormone-replacement therapy, oral anticoagulants
Middle cerebral artery signal absent on Doppler ultrasound

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)
Dynamic (adaptive) random allocation methods, i.e. minimisation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
One hundred and thirty-five participants will be recruited for this study. This allows for 20% attrition as 108 participants are required to give 80% power to detect a significant (p<0.05) 5% change in cerebrovascular function, based on a 10% standard deviation observed in previously run studies that measure cerebrovascular function.

Data will presented as mean ± standard error of the mean (SEM). These data will be normally distributed and analysed using 2 (pre- and post- exercise prescription) x 2 (baseline and 16 weeks post intervention for each level of exercise) factor repeated analysis of variance (ANOVA) using SPSS or the like thereof.. The repeated measures ANOVA will be performed on the CVR to hypercapnia and cognitive stimuli, as well as the overall cognitive performance to determine the significance of differences between each level of exercise. P-value < 0.05 for the primary outcome (CVR) will be considered significant. A sequential Bonferroni procedure for multiple comparisons of the remaining measurements will be used. Pearson’s correlation analyses with false discovery adjustments, which is used to minimise the occurrence of a type 1 error (i.e. a false-positive), will used to evaluate baseline measurements in CVR to hypercapnia and/or cognitive stimuli, physiological measurements and psychological markers. A P-value < 0.025 for the remainder measures will be considered significant.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Other reasons/comments
Other reasons
COVID-19
Date of first participant enrolment
Anticipated
Actual
1/06/2019
Date of last participant enrolment
Anticipated
28/02/2020
Actual
28/02/2020
Date of last data collection
Anticipated
30/06/2020
Actual
28/02/2020
Sample size
Target
135
Accrual to date
Final
28
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 303145 0
University
Name [1] 303145 0
University of Southern Queensland
Country [1] 303145 0
Australia
Primary sponsor type
University
Name
University of Southern Queensland
Address
University of Southern Queensland
West Street
Toowoomba Qld 4350
Australia
Country
Australia
Secondary sponsor category [1] 303142 0
None
Name [1] 303142 0
Address [1] 303142 0
Country [1] 303142 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303694 0
University of Southern Queensland Human Ethics Committee
Ethics committee address [1] 303694 0
Ethics committee country [1] 303694 0
Australia
Date submitted for ethics approval [1] 303694 0
20/11/2018
Approval date [1] 303694 0
19/03/2019
Ethics approval number [1] 303694 0
H19REA007

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

Contacts
Principal investigator
Name 94518 0
Mr Edward Bliss
Address 94518 0
University of Southern Queensland
West Street
Toowoomba Qld 4350
Australia
Country 94518 0
Australia
Phone 94518 0
+61 746315477
Fax 94518 0
Email 94518 0
[email protected]
Contact person for public queries
Name 94519 0
Edward Bliss
Address 94519 0
University of Southern Queensland
West Street
Toowoomba Qld 4350
Australia
Country 94519 0
Australia
Phone 94519 0
+61 746315477
Fax 94519 0
Email 94519 0
[email protected]
Contact person for scientific queries
Name 94520 0
Edward Bliss
Address 94520 0
University of Southern Queensland
West Street
Toowoomba Qld 4350
Australia
Country 94520 0
Australia
Phone 94520 0
+61 746315477
Fax 94520 0
Email 94520 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Only data underlying published results collected during the trial will be made available, after de-identification.
When will data be available (start and end dates)?
Once published and Edward Bliss has completed his PhD (~31/12/2020). Hence, immediately following publication of Edward's thesis and any journal articles that are generated throughout the course of the study. No end date
Available to whom?
Individual data will also be available to the participants of the study on request.
De-identified data will be available for journal/conference proceedings.
Researchers on the project (i.e. co-investigators).
Available for what types of analyses?
Only to achieve the aims in the approved proposal
How or where can data be obtained?
Restricted access via USQ data portal (password protected) and this will be granted subject to approvals by Principal Investigator ([email protected]).


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.