Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000489392
Ethics application status
Approved
Date submitted
2/09/2008
Date registered
30/09/2008
Date last updated
19/11/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
The Study of Mental Activity and Regular Training for the Prevention of Cognitive Decline in at Risk Individuals: The SMART Trial
Scientific title
The Study of Mental Activity and Regular Training for the Prevention of Cognitive Decline in at Risk Individuals: The SMART Trial
Secondary ID [1] 280457 0
None
Universal Trial Number (UTN)
Trial acronym
SMART
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cognitive Impairment 3632 0
Condition category
Condition code
Neurological 3717 3717 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cognitive Training Intervention - The SMART Trial suite of cognitive training exercises are aimed at computer-based multimodal, multi-domain and task load-graded training in the areas of memory, executive function, attention and speed of information processing. We have chosen a subset of exercises from the COGPACK package as these were developed at a recognized neurorehabilitation centre, are based largely on well established neuropsychological tests and principles and, moreover, their effective use with psychiatric patients has been reported (McGurk et al 2005; 2007).

Training frequency was 3 days per week for the first 30 participants. It was reduced to 2 days per week for the remaining subjects as a means to reduce participant burden which was determined to be a major barrier to recruitment due to transportation difficulties in this cohort with mild cognitive impairment. Each participant in this arm will participant in two or three 45-min sessions/week (total of 52-78 sessions over 6 months). The sessions will be conducted in small groups (maximum of 10 participants), with each participant working through the memory, information processing, attention and problem solving tasks at their own pace.


Participants will complete 4 exercises per session; the mix of exercise per session is one verbal memory exercise, one visual memory exercise, and the other two rotating between attention, information speed, and executive exercises in a balanced fashion across the sessions Fourteen exercises have been chosen. Thirteen of the 14 exercises require a simple touch-screen response with no mouse operation and in this way will avoid training difficulties in the computer-naïve. Resistance Training Intervention - The progressive resistance training (PRT) will be conducted 2-3 days per week, 45 minutes per session, for 26 weeks. The subjects will be trained by experienced exercise trainers in a medically-supervised setting at a ratio of 1 trainer for 4-5 subjects.
PRT intensity was prescribed at 80% of current measured or estimated strength on each exercise using pneumatic resistance machines. This was achieved by initially measuring the 1RM twice at baseline and again after every 6 training sessions during the 6 mo intervention. The load was then set at 80% of the most recently determined 1RM, and increased by about 3% for every subsequent session as tolerated, until the next 1RM determination. Tolerance was assessed by keeping the Borg rating of perceived exertion between 15-18, adjusting the load up or down as needed to achieve this. In addition, assessor observation of pain, accessory muscle use or violations of form were used to titrate the load. For free weight exercises in which 1RM testing could not be done, the Borg scale and assessor evaluation of effort were used to monitor progression and alter loads.

We have successfully and safely used this regimen since 1988 in frail elders up to the age of 103 to induce anabolic adaptations, as well as robust physical, functional, and psychological benefits (Singh 2002). Combined Cognitive and Exercise Intervention - This group will get both the cognitive and exercise training on the same day (90 minute sessions), 2-3 sessions per week for 26 weeks. In order to take advantage of the enhanced attention and learning exhibited after an acute bout of exercise in both animal and human studies, the cognitive training will take place after the progressive resistance training. The subjects in the intervention groups will be randomised into one of the four groups: 1. Cognitive Training + Sham PRT, 2. PRT + Sham Cognitive Training, 3. Cognitive Training + PRT and 4. Sham Cognitive Training + Sham PRT.
Intervention code [1] 3271 0
Prevention
Comparator / control treatment
Sham Cognitive and Sham Exercise Control Groups - In these groups, subjects will receive versions of cognitive exercise (in the form of lectures, Sham Cognitive) and physical exercise (seated and standing gentle exercises, Sham Exercise) that are considered to be ineffective with regards to the cognitive and neurological outcomes of this trial. The total session length will be 45 minutes, and all training will be supervised in groups of approximately 10. Lectures seated gentle exercise. This group will train for 2 sessions per week for 26 weeks
Control group
Placebo

Outcomes
Primary outcome [1] 4618 0
Primary Outcomes: Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) for global cognitive function and subsets. Functional independence attributed to cognitive impairment was be assessed by the Informant Bayer-Activities of Daily Living (B-ADL) questionnaire.
Timepoint [1] 4618 0
Baseline, 6 months, and 18 months
Secondary outcome [1] 7790 0
Secondary Cognitive outcomes included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR), Matrices and Similarities subtests of Wechsler Adult Intelligence Scale 3rd Edition (WAIS-III) , Trail Making Test (TMT), Symbol Digit Modalities Test (SDMT), Logical Memory I and II subtests of the Wechsler Memory Scale 3rd Edition (WMS-III), Benton Visual Retention Test -Revised 5th Edition (BVRT-R), Category fluency, Controlled Oral Word Association Test (COWAT), and the General Practitioner assessment of Cognition (GP-Cog).

Secondary mood and affect outcomes: Psychological outcomes including, Short Form 36 (SF-36), Quality of Life Scale (QoL), Life Satisfaction Scale (LSS), Scale of Psychological Well-being (SPWB), Depression Anxiety and Stress Scale (DASS 21),Memory Awareness Rating Scale (MARS), Geriatric Depression Scale (GDS), Subjective Memory Concerns (SMC),

Secondary physiological outcomes included: Graded Treadmill exercise stress test with exercise capacity (VO2 measured via metabolic cart and mask apparatus; Medgraphics), body composition (waist, height (stretch stature), naked fasting weight), blood pressure ( inclusive also of ankle-brachial index, orthostatic blood pressure), 1RM muscle strength of lower and upper limbs, static and dynamic balance tests, gait speed, sit-to-stand, grip strength, nutritional biochemistry, insulin resistance and glucose homeostasis, genetic polymorphism, cortisol stress response, inflammatory biomarkers, habitual levels of physical activity and sleep. Pet care, Self-reported size and satisfaction of social support (DUKE), and community health services utilization.
Timepoint [1] 7790 0
Baseline, 6 months, and 18 months and 72-months
Secondary outcome [2] 319008 0
Telephone administered versions of Mood/Affect and functional questionnaires listed in clinical assessment time-points BL, 6, 18, 72) with the additional of the Telephone interview for cognitive status (TICS) questionnaire and activity log for week prior to call.
Timepoint [2] 319008 0
24, 36, 48, 60, 72, 84-month Telephone status check interviews (post intervention)
Secondary outcome [3] 319009 0
Diet survey, 3-day food diary, Stroop computer based cognitive test
Timepoint [3] 319009 0
72-month clinical follow up assessment and follow up, SMARTlife program

Eligibility
Key inclusion criteria
Age 55 or above with a corrected Mini-Mental State Exam score of 29 or below; willing to have multiple cognitive, physical and imaging assessments over 12 months; has a suitable informant (if available) that is willing and able to answer questions about their past and current condition; understands and agrees to comply with random allocation process; has telephone at home. There will be 3-stage screening, which includes: Telephone screen by RA of participant and informant (if available) for willingness to participate, sedentary status, no exclusionary medical history, and TICS < or equal to 30. This will be followed by In-person screen by neuropsychologist and later on by In-person screen by geriatrician/stress testing (to ascertain unstable or unsuitable medical conditions).
Minimum age
55 Years
Maximum age
120 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Diagnosis of dementia, more than 1 stroke or transient ischemic attack (TIA) or major degenerative neurological disease; current psychotic illness diagnosis, current/past alcohol or drug abuse; current or past use of prescribed cognitive enhancing medication such as cholinesterase inhibitor, nootropic agents; no competency in English, or unable to read and write or use computers due to sensory impairment; high participation in mental activity; current participation in planned structured exercise of any kind other than low- intensity walking 1 or more days per week; Activities of daily living (ADL) or instrumental activities of daily living (IADL) impairment due to cognition; non-ambulatory; contraindications to high intensity progressive resistance training (PRT) or maximal exercise testing

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)
Written informed consent will be required prior to any testing or randomisation.
Assignments will be placed in sealed opaque envelopes and designated “Blue Group” for cognitive training, “Red Group” for PRT, “Yellow Group” for cognitive training + PRT, and “Green Group” for sham exercise.

The subject will open these envelopes after completion of all baseline testing. Subjects who dropout prior to completion of baseline testing will not be randomised.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Subjects are randomised after the baseline assessment has been completed to: 1. Cognitive training + sham PRT 2. PRT + sham cognitive training 3. Cognitive training + PRT 4. Sham cognitive + sham PRT Randomisation is at the level of the individual patient, and will be stratified by gender and age. The list will be generated and maintained by a research assistant not otherwise involved in the study. The sequential treatment assignments are based on a computer-generated randomisation scheme (by using the Web site www.randomization.com set up by Dr Gerard E. Dallal). Stratification by gender and age group (55-74 and 75+) will be planned, in anticipation of the greater prevalence of women in the targeted cohort, and potential age effects on underlying pathophysiology of cognitive impairment and adaptation to training.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/09/2008
Actual
30/09/2008
Date of last participant enrolment
Anticipated
Actual
29/06/2011
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
100
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 3736 0
Government body
Name [1] 3736 0
National Health and Medical Research Council (NHMRC)
Country [1] 3736 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Exercise and Sport Science, C42, Faculty of Health Sciences, University of Sydney
East Street, Lidcombe, NSW, 2141, Australia
Country
Australia
Secondary sponsor category [1] 3352 0
University
Name [1] 3352 0
University of New South Wales
Address [1] 3352 0
University of New South Wales
Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, 2031, Australia
Country [1] 3352 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5789 0
University of Syndey Human Research Ethics Committee
Ethics committee address [1] 5789 0
Ethics committee country [1] 5789 0
Australia
Date submitted for ethics approval [1] 5789 0
Approval date [1] 5789 0
18/07/2008
Ethics approval number [1] 5789 0
06-2008/11094
Ethics committee name [2] 5869 0
Sydney South West Area Health Service Ethics Review Committee (RPAH Zone)
Ethics committee address [2] 5869 0
Research Development Office
Level 8, Building 14
Royal Prince Alfred Hospital
Camperdown NSW 2050
Ethics committee country [2] 5869 0
Australia
Date submitted for ethics approval [2] 5869 0
Approval date [2] 5869 0
29/05/2008
Ethics approval number [2] 5869 0
08/RPAH/106
Ethics committee name [3] 5870 0
The University of New South Wales Human Research Ethics Committee
Ethics committee address [3] 5870 0
Rupert Myers Building
c/o Research Office/Ethics
Gate 14
Barker St
Kensington
NSW 2033
Ethics committee country [3] 5870 0
Australia
Date submitted for ethics approval [3] 5870 0
Approval date [3] 5870 0
22/07/2008
Ethics approval number [3] 5870 0

Summary
Brief summary
Over 200,000 individuals are affected by dementia in Australia, with many more individuals at-risk by virtue of borderline cognitive impairment. The personal, social and economic impact is therefore significant and projected to increase due to the ageing of the population. Even relatively modest goals, however, such as delaying the onset of dementia by a few years could have a large impact on the burden to individuals and society. New strategies aimed at preventing cognitive decline are therefore an urgent priority. In this regard, there is mounting evidence that involvement in a variety of mentally and physically stimulating activities throughout life may be important for optimal brain function and a reduced occurrence of memory problems in older adults. There is also some evidence that even when started in later life, mental and physical exercises can maintain or improve brain function compared to those who do not engage in such activities. However, the best type or combination of activities to achieve such benefits is far from clear. In addition, whether such techniques would work in those who have already developed mild changes in mental function is largely unknown. Therefore, we have designed a robust clinical trial in which individuals who have early changes in memory or thinking ability without an identified cause will be randomly assigned to mental exercises, weight lifting exercise, both interventions together, or a control condition. Participants will have their cognitive abilities tested after 1 year to ascertain whether lasting benefits do occur. In addition, brain size and biochemistry will be assessed using sophisticated magnetic resonance imaging studies. Associated improvements in fitness, body fat, mood, risk for other chronic diseases, and independence and quality of life will also be measured. This study will therefore provide the first comparison of the isolated and combined effects of these two interventions in an older sample at risk for dementia, as well as provide new insights into possible biological changes underlying these benefits. Statistical Analysis Strategy: Primary outcomes will be analysed by intention-to-treat analysis with imputation of missing data using the expectation maximization algorithm and/or mixed model regression techniques. Secondary analyses of primary outcomes will include all available data and per protocol analytic strategies, in order to investigate any potential dose-response effect of our interventions. Secondary outcomes will be analysed using all available data.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28844 0
Prof Maria A. Fiatarone Singh
Address 28844 0
Exercise and Sport Science, C42, Faculty of Health Sciences, University of Sydney East Street, Lidcombe, NSW, 2141, Australia
Country 28844 0
Australia
Phone 28844 0
612-9351-9755
Fax 28844 0
Email 28844 0
maria.fiataronesingh@sydney.edu.au
Contact person for public queries
Name 12001 0
Prof Maria Fiatarone Singh
Address 12001 0
Exercise and Sport Science, C42, Faculty of Health Sciences, University of Sydney
East Street, Lidcombe, NSW, 2141, Australia
Country 12001 0
Australia
Phone 12001 0
612-9351-9755
Fax 12001 0
02 93519204
Email 12001 0
maria.fiataronesingh@sydney.edu.au
Contact person for scientific queries
Name 2929 0
Prof Maria Fiatarone Singh
Address 2929 0
Exercise and Sport Science, C42, Faculty of Health Sciences, University of Sydney
East Street, Lidcombe, NSW, 2141, Australia
Country 2929 0
Australia
Phone 2929 0
612-9351-9755
Fax 2929 0
02 93519204
Email 2929 0
maria.fiataronesingh@sydney.edu.au

No information has been provided regarding IPD availability


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
SourceTitleYear of PublicationDOI
EmbaseMediation of Cognitive Function Improvements by Strength Gains After Resistance Training in Older Adults with Mild Cognitive Impairment: Outcomes of the Study of Mental and Resistance Training.2017https://dx.doi.org/10.1111/jgs.14542
EmbaseStudy of Mental Activity and Regular Training (SMART) in at risk individuals: a randomised double blind, sham controlled, longitudinal trial.2011
N.B. These documents automatically identified may not have been verified by the study sponsor.