Trial from ANZCTR


Trial ID ACTRN12608000489392
Trial Status: Registered
Date Submitted: 2/09/2008
Date Registered: 30/09/2008
Prospectively registered

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Public title The Study of Mental Activity and Regular Training for the Prevention of Cognitive Decline in at Risk Individuals: The SMART Trial
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Study title in 'Participant- Intervention- Comparator- Outcome (PICO)' format The Study of Mental Activity and Regular Training for the Prevention of Cognitive Decline in at Risk Individuals: The SMART Trial
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Secondary ID [1] 280457 0
None
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UTN
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Trial acronym SMART
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Health condition(s) or problem(s) studied:
Cognitive Impairment 3632 0
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Condition category: Condition code:
Neurological Neurodegenerative diseases
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3717 3717 0 0

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Descriptions 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.
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Intervention Code:
Prevention 3271 0
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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
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Control group Placebo
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Primary Outcome: Cognitive performance; involves assessing attention, memory, language, problem solving, and speed through clinician- and patient-administered questionnaires: Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog), Matrices and Similarities, Trail Making Test (TMT), Symbol Digit Modalities Test (SDMT), Logical Memory, Benton Visual Retention Test, Category fluency, Controlled Oral Word Association Test (COWAT). In conjunction with cognitive performance, functional independence attributed to cognitive impairment will be assessed by the Informant Bayer-Activities of Daily Living (B-ADL) questionnaire. 4618 0
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Timepoint: Baseline, 6 months, and 18 months 4618 0
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Secondary Outcome: Functional independence attributed to physical impairment will be assessed by the Participant and Informant Bayer-Activities of Daily Living (B-ADL) questionnaire. In addition, psychological outcomes including, Short Form 36 (SF-36), Quality of Life Scale, Life Satisfaction Scale, Scale of Psychological Well-being (SPWB), Depression Anxiety and Stress Scale (DASS 21) and Memory Awareness Rating Scale (MARS). 7790 0
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Timepoint: Baseline, 6 months, and 18 months 7790 0
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Secondary Outcome: Physical testing includes exercise stress test, exercise capacity, body composition, blood pressure (ankle-brachial index, orthostatic blood pressure), muscle strength, balance, gait speed, nutritional biochemistry, insulin resistance and glucose homeostasis, genetic polymorphism, cortisol stress response, inflammatory biomarkers, habitual levels of physical activity and sleep. Self-reported size and satisfaction of social support, and community health services utilization. 8063 0
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Timepoint: Baseline, 6 months, and 18 months 8063 0
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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).
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Minimum age 55 Years
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Maximum age 120 Years
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Gender Both males and females
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Healthy volunteers? No
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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
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Study type Interventional
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Purpose of the study Treatment
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Allocation to intervention Randomised controlled trial
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Describe the 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.
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Describe the 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.
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Masking / blinding Blinded (masking used)
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Who is / are masked / blinded (choose all that apply)


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Assignment Factorial
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Other design features
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Type of endpoint(s) Efficacy
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Statistical Methods/Analysis
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Phase Not Applicable
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Anticipated date of first participant enrolment 30/09/2008
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Date of first participant enrolment
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Anticipated date last participant recruited/enrolled
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Actual date last participant recruited/enrolled
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Target sample size 100
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Recruitment status Completed
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Recruitment in Australia

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Recruitment outside Australia

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Funding Source: Government body 3736 0
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Name: National Health and Medical Research Council (NHMRC) 3736 0
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Address: National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
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Country: Australia 3736 0
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Primary Sponsor University
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Name: University of Sydney
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Address: Exercise and Sport Science, C42, Faculty of Health Sciences, University of Sydney
East Street, Lidcombe, NSW, 2141, Australia
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Country: Australia
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Secondary Sponsor: University 3352 0
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Name: University of New South Wales 3352 0
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Address: University of New South Wales
Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, 2031, Australia
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Country: Australia 3352 0
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Has the study received approval from at least one Ethics Committee? Yes
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Ethics Committee name: University of Syndey Human Research Ethics Committee 5789 0
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Address: 5789 0
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Country: Australia 5789 0
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Approval Date: 18/07/2008 5789 0
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Submitted Date: 5789 0
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HREC: 06-2008/11094 5789 0
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Ethics Committee name: Sydney South West Area Health Service Ethics Review Committee (RPAH Zone) 5869 0
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Address: Research Development Office
Level 8, Building 14
Royal Prince Alfred Hospital
Camperdown NSW 2050
5869 0
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Country: Australia 5869 0
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Approval Date: 29/05/2008 5869 0
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Submitted Date: 5869 0
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HREC: 08/RPAH/106 5869 0
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Ethics Committee name: The University of New South Wales Human Research Ethics Committee 5870 0
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Address: Rupert Myers Building
c/o Research Office/Ethics
Gate 14
Barker St
Kensington
NSW 2033
5870 0
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Country: Australia 5870 0
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Approval Date: 22/07/2008 5870 0
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Submitted Date: 5870 0
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HREC: 5870 0
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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.
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Trial website
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Public Notes
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Principal Investigator
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Contact person for public queries
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Name: Maria Fiatarone Singh
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Address: Exercise and Sport Science, C42, Faculty of Health Sciences, University of Sydney East Street, Lidcombe, NSW, 2141, Australia
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Country: Australia
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Tel: 612-9351-9755
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Fax: 02 93519204
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Email: maria.fiataronesingh@sydney.edu.au
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Contact person for scientific queries
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Name: Maria Fiatarone Singh
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Address: Exercise and Sport Science, C42, Faculty of Health Sciences, University of Sydney East Street, Lidcombe, NSW, 2141, Australia
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Contact person responsible for updating information
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Name: Maria Fiatrone Singh
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Address: Exercise and Sport Science, C42, Faculty of Health Sciences, University of Sydney East Street, Lidcombe, NSW, 2141, Australia
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Addition Cancer fields
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