Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000700235
Ethics application status
Approved
Date submitted
17/04/2018
Date registered
30/04/2018
Date last updated
30/04/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Optimising exercise for cognitive function in older adults
Scientific title
Optimising exercise for cognitive function in older adults: joining the dots between exercise intensity, hippocampal volume and novel biomarkers
Secondary ID [1] 289712 0
Nil known
Universal Trial Number (UTN)
U1111-1185-5102
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cognitive decline 299527 0
Dementia 299528 0
Alzheimer's Disease 299529 0
Mild cognitive impairment 299530 0
Condition category
Condition code
Neurological 299505 299505 0 0
Studies of the normal brain and nervous system
Neurological 299506 299506 0 0
Dementias
Neurological 299507 299507 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised to one of three exercise interventions - low intensity (control), moderate intensity and aerobic intensity - and visit the exercise laboratory three times per week for six months. All training sessions will be supervised by qualified Exercise Scientists and Exercise Physiologists and will be conducted in small-group settings. Exercise intensity will be regularly monitored via heart rate and rating of perceived exertion (RPE) and will be recorded at regular intervals during the training sessions.

Attendance, adherence and feasibility
All data for training sessions will be recorded in an individual participant training diary, attendance will be calculated as the number of sessions attended divided by the total number of sessions available to attend. In the control group adherence will be calculated as the number of exercises completed, the moderate intensity group will be the total minutes where the target heart rate was maintained divided by the total exercise time, and the high-intensity condition adherence will be calculated as the number of intervals where the target heart rate is achieved divided by the total number of intervals completed. Attendance and adherence will be used to comment on the feasibility of the exercise paradigms in the target population.

Moderate-intensity exercise training condition
The moderate intensity exercise protocol will consist of 45-min continuous treadmill walking exercise at 60-70% of peak heart rate, with a 10-minute warm-up whereby participants increase the intensity of their walking to reach the target heart rate, a 30-minute core session, and a 5-minute cool down.

Aerobic interval exercise training condition
Participants randomised to aerobic interval training will complete a light 10-minute warm-up followed by four, four-minute working periods at 85-95% of peak heart rate interspersed by three-minute active breaks at 60-70% peak heart rate followed by a 5-minute cool-down, totalling 40-minutes of treadmill exercise.
Intervention code [1] 295341 0
Prevention
Intervention code [2] 295342 0
Lifestyle
Intervention code [3] 295343 0
Treatment: Other
Comparator / control treatment
Control condition
Participants randomised to the low-intensity exercise (control) condition will attend an indoor 40-minute fit ball, balance, stretching and toning class facilitated by an Exercise Scientist/Physiologist. The program will include a range of 5-8 stretching, balance, range of motion and relaxation tasks in a small group setting, with a 10-minute warm up, 20-minute core class, and 10-minute cool down. This group will serve to control for confounding variables such as attention, participation, social interaction, physical exercise received by travelling to and from the exercise centre and changes in lifestyle secondary to study participation.
Control group
Active

Outcomes
Primary outcome [1] 299259 0
Measures of spatio-visual cognitive function (CANTAB)
Timepoint [1] 299259 0
Baseline, interim (month 1, 2, 3, 4, and 5), post-intervention (month 6) and interim and post-follow-up (month 9 and 12). Month 6 (post-intervention) is the primary timepoint of interest.
Primary outcome [2] 299260 0
Changes in hippocampal volume as measured by multimodal 7T MRI.
Timepoint [2] 299260 0
Baseline, post-intervention (6 months) , and post-follow-up (12 months). Month 6 (post-intervention) is the primary timepoint of interest.
Primary outcome [3] 299261 0
Changes in physiological fitness, as determined by peak aerobic capacity measured via indirect calirometry using an automated metabolic cart
Timepoint [3] 299261 0
Baseline, interim (3 months), post-intervention (6 months) and post-follow-up (9 and 12 months). Month 6 (post-intervention) is the primary timepoint of interest.
Secondary outcome [1] 326668 0
Measures of global cognitive function (ACE-R)
Timepoint [1] 326668 0
Baseline, interim (month 3), post-intervention (month 6),and interim and post-follow-up (month 9 and 12).
Secondary outcome [2] 326669 0
Measures of spatial navigation (hMWM)
Timepoint [2] 326669 0
Baseline, interim (month 3), post-intervention (month 6),and interim and post-follow-up (month 9 and 12).
Secondary outcome [3] 326670 0
Changes in physiologic fitness (exercise efficiency), as determined via automated indirect calirometry
Timepoint [3] 326670 0
Baseline, interim (3 months), post-intervention (6 months) and post-follow-up (9 and 12 months).
Secondary outcome [4] 326671 0
Changes in blood biomarkers (growth factors, inflammatory factors, hormones, DNA methylation, RNA expression). This is an exploratory outcome.
Timepoint [4] 326671 0
Baseline, interim (month 1, 2, 3, 4, and 5), post-intervention (month 6) and interim and post-follow-up (month 9 and 12)
Secondary outcome [5] 326673 0
Changes in exercise response of biochemical factors (growth factors, inflammatory factors and hormones) following acute exercise. This is an exploratory outcome.
Timepoint [5] 326673 0
Month 0, 1, 2, 3, 4, 5, 6 during the intervention.
Secondary outcome [6] 326674 0
Measures of depression and anxiety (DASS)
Timepoint [6] 326674 0
Baseline, interim (3 months), post-intervention (6 months) and post-follow-up (9 and 12 months).
Secondary outcome [7] 326675 0
Measures of quality of life (SF-36)
Timepoint [7] 326675 0
Baseline, interim (3 months), post-intervention (6 months) and post-follow-up (9 and 12 months).
Secondary outcome [8] 326676 0
Measures of habitual physical activity (actigraphy)
Timepoint [8] 326676 0
Baseline, interim (3 months), post-intervention (6 months) and post-follow-up (9 and 12 months).
Secondary outcome [9] 326678 0
Measures of sleep quality and quanity (ISI)
Timepoint [9] 326678 0
Baseline, interim (3 months), post-intervention (6 months) and post-follow-up (9 and 12 months).
Secondary outcome [10] 345814 0
Measures of sleep quality and quanity (PSQI)
Timepoint [10] 345814 0
Baseline, interim (3 months,), post-intervention (6 months) and post-follow-up (9 and 12 months)
Secondary outcome [11] 345815 0
Changes in physiologic fitness (heart rate recovery) as assessed via 12-lead ECG during 5-minutes of seated rest following an exercise stress test
Timepoint [11] 345815 0
Baseline, interim (3 months, post-intervention (6 months, and post-follow-up (9 and 12 months)
Secondary outcome [12] 345816 0
Changes in functional fitness using the short physical performance battery
Timepoint [12] 345816 0
Baseline, interim (3 months), post-intervention (6 months)) and post-follow-up (9 and 12 months)
Secondary outcome [13] 345817 0
Changes in physiologic fitness ( body composition) as determined by dual-energy x-ray absorptiometry
Timepoint [13] 345817 0
Baseline, interim (3-months), post-intervention (6 months) and post-follow-up (9 and 12 months).
Secondary outcome [14] 345963 0
Changes in hippocampal sub-field volumes (including dentate gyrus to quantify neurogenesis) as measured by 7T stuctural MRI.
Timepoint [14] 345963 0
0, 6, and 12 months
Secondary outcome [15] 345964 0
Changes in resting and active state functional connectivity as measured by multimodal 7T MRI
Timepoint [15] 345964 0
0, 6 and 12 months
Secondary outcome [16] 345965 0
Changes in physiologic fitness (ventilatory threshold), as determined via automated indirect calirometry
Timepoint [16] 345965 0
Baseline, interim (3-months), post-intervention (6-months) and post-follow-up (9- and 12-months)
Secondary outcome [17] 345966 0
Changes in physiologic fitness (peak heart rate), as determined via 12-lead ECG during an exercise stress test
Timepoint [17] 345966 0
Baseline, interim (3 months), post-intervention (6 months), and post-follow-up (9 and 12 months)
Secondary outcome [18] 346206 0
Changes in physiologic fitness (oxygen uptake efficiency slope), as determined via automated indirect calirometry.
Timepoint [18] 346206 0
Baseline, interim (3-months), post-intervention (6-months) and post-follow-up (9- and 12-months)
Secondary outcome [19] 346207 0
Changes in physiological fitness (peak cardiac output) as estimated from 12-lead ECG during an exercise stress test.
Timepoint [19] 346207 0
Baseline, interim (3-months), post-intervention (6-months) and post-follow-up (9- and 12-months).

Eligibility
Key inclusion criteria
• Aged 65 – 85 years at the time of study inclusion
• Able and willing to provide written informed consent
• Able to communicate in English
• No history of stroke or brain trauma
• Stratified as ‘not high risk of experiencing a cardiac event during exercise’ according to the adult pre-exercise screening system (ESSA, 2012)
• No presently diagnosed mental illness or significant cognitive impairment
• Not be medicated for dementia
• Healthy body mass index 18.5 – 30 kg.m-2
• Be able and willing to commit to the duration of the exercise program.
Minimum age
65 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Younger than 65 years or older than 85 years of age
• Illness or disability that preclude exercise or hinder completion of the study
• Poorly controlled hypertension, cardiomyopathy, unstable angina, heart failure or severe arrhythmia, cancer, or chronic communicable infectious diseases
• Current use of antipsychotics and/or antidepressants
• Current or planned use of dehydroepiandrosterone, testosterone, transdermal oestrogens or other medications known to affect the growth hormone releasing hormone/growth hormone/insulin-like growth factor-1 axis.
• Currently diagnosed significant psychiatric illness, such as depression or schizophrenia, or dementia
• Any contraindication for 7 Tesla MRI investigation, including joint replacements, stents, bullet or shrapnel wounds and metal in the eye
• Tobacco use, excessive alcohol intake (more than four alcoholic drinks per day), excessive caffeine intake (more than four cups of coffee per day)
• Excessive exercise involvement (more than twice the weekly recommendations for adults or >600 minutes moderate to vigorous exercise)
• Test results that indicate study participation is unsafe
• Participation in conflicting studies.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Random generated numbers will be placed into an envelope, which will be opened after the baseline assessment is complete. The randomisation envelopes will be stored in a locked filing cabinet in the principle investigators office, and will only be accessed by the principle investigator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation to intervention and control groups will be completed using random computer-generated numbers, which will be generated prior to participant assessment and will be stratified according to sex.
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
Based on an a-priori sample size calculation (alpha=0.05, power=0.80, effect size=0.50 (moderate), standard deviation=0.50, Vanderbilt®), we will require 64 participants per group. In order to achieve this sample size, we will approach and screen 1000 potential participants, From this number, we anticipate that approxcimately half will be eligible fror the study, and we hope to recruit 60% of these. To allow for 30% drop-out, 100 participants per group will be recruited. Participants will be male and female aged 65-85 years at the time of study inclusion, must fulfil all inclusion criteria and not exhibit any exclusion criteria.
This project will implement an intention-to-treat statistical analysis model. Data will be analysed using Microsoft Excel 2007, SPSS (version 22.0, SPSS, Inc., Chicago, IL, USA) and GraphPad Prism® statistical software packages. Normality of the distribution for outcome measures will be tested using the Shapiro-Wilk test with an alpha level <0.05. Where the data are not normally distributed, data will be log-transformed and re-checked for normality of distribution. Where log-transformed data are not normally distributed, non-parametric analyses including the Spearman’s correlation coefficient, Wilcoxon signed-rank test and Friedman’s analysis of variance followed by the Wilcoxon signed-rank test will be employed. Analyses for normally-distributed data will include standard descriptive statistics and frequency counts. Pearson’s correlation coefficients or the non-parametric equivalent will be used to determine associated between variables. Paired and independent samples t-tests will be used to test for within- and between-group differences and two-way repeated measures analysis of variance will determine group x time effects for the training allocation. Variables that are significantly different at baseline will be included in univariate and multivariate logarithmic and linear regression analyses to predict cognitive function. The Queensland Brain Institute has access to biostatisticians who will be consulted for statistical analysis of data.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
27/02/2017
Date of last participant enrolment
Anticipated
31/12/2018
Actual
Date of last data collection
Anticipated
31/12/2019
Actual
Sample size
Target
300
Accrual to date
130
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 295431 0
Charities/Societies/Foundations
Name [1] 295431 0
The Stafford Fox Medical Research Foundation
Country [1] 295431 0
Australia
Primary sponsor type
University
Name
The Univeristy of Queensland
Address
The University of Queensland
St Lucia,
Brisbane, Australia
4072
Country
Australia
Secondary sponsor category [1] 294251 0
None
Name [1] 294251 0
NA
Address [1] 294251 0
NA
Country [1] 294251 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296763 0
Bellberry Limited
Ethics committee address [1] 296763 0
Ethics committee country [1] 296763 0
Australia
Date submitted for ethics approval [1] 296763 0
22/06/2016
Approval date [1] 296763 0
05/08/2016
Ethics approval number [1] 296763 0
2016-01-038-A1

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

Contacts
Principal investigator
Name 67538 0
Dr Mia Schaumberg
Address 67538 0
The School of Human Movement and Nutrition Sciences
Building 26B (C0nnell)
Corner Blair Drive and Union Road
The University of Queensland
St Lucia, 4072
Country 67538 0
Australia
Phone 67538 0
+61 7 3346 8770
Fax 67538 0
Email 67538 0
[email protected]
Contact person for public queries
Name 67539 0
Mia Schaumberg
Address 67539 0
The UQ Centre for Exercise and Healthy Brain Ageing
Room 226 – 228, Building 26 (Connell)
Corner Blair Drive and Union Road
The University of Queensland
St Lucia, 4072
Country 67539 0
Australia
Phone 67539 0
+61 7 3443 3209
Fax 67539 0
Email 67539 0
[email protected]
Contact person for scientific queries
Name 67540 0
Mia Schaumberg
Address 67540 0
The UQ Centre for Exercise and Healthy Brain Ageing
Room 226 – 228, Building 26 (Connell)
Corner Blair Drive and Union Road
The University of Queensland
St Lucia, 4072
Country 67540 0
Australia
Phone 67540 0
+61 7 3346 8770
Fax 67540 0
Email 67540 0
[email protected]

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No Supporting Document Provided



Results publications and other study-related documents

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