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Trial record 1 of 2 for:    SYNERGIC | Canada
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SYNchronizing Exercises, Remedies in GaIt and Cognition (SYNERGIC)

This study is currently recruiting participants.
Verified June 2017 by Manuel Montero Odasso, Lawson Health Research Institute
Sponsor:
ClinicalTrials.gov Identifier:
NCT02808676
First Posted: June 22, 2016
Last Update Posted: June 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Manuel Montero Odasso, Lawson Health Research Institute
  Purpose
The proposed SYNERGIC trial is uniquely designed to evaluate the effect of aerobic and progressive resistance training exercises, combined with cognitive training and Vitamin D3 supplementation, in cognition and mobility in older adults with Mild Cognitive Impairment (MCI).

Condition Intervention
Mild Cognitive Impairment Dietary Supplement: Vitamin D3 Other: Exercises (E) Other: Cognitive Training (CT) Other: placebo D3 Other: control cognitive training Other: Placebo exercise

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: SYNchronizing Exercises, Remedies in GaIt and Cognition (SYNERGIC): A Randomized Controlled Double Blind Trial

Resource links provided by NLM:


Further study details as provided by Manuel Montero Odasso, Lawson Health Research Institute:

Primary Outcome Measures:
  • Change in global cognition assessed using the ADASCog(13 and Plus modalities). [ Time Frame: baseline and at 20 weeks (after interventions finalised) ]
    Global cognition will be assessed using the cognitive section of the Alzheimer Disease Assessment Scale-plus EF+FA (ADAS-Cog-plus). This scale consists of 10 brief cognitive tests assessing memory, language, executive function, praxis, and instrumental activities of daily living. The ADAS-Cog has been a significant outcome measure in numerous trials with MCI and AD. The ADAS-Cog-plus has marked advantages as an outcome measure in MCI populations since incorporates items concerning executive function (EF) and functional abilities (FA). Scores in the ADASCog-plus (EF+FA) range from 0 to 90, with higher scores indicating better cognitive performance.


Secondary Outcome Measures:
  • Change in cognition assessed as the CCNA Cognitive Battery. [ Time Frame: baseline at 20 weeks (after interventions finalised) ]
    The Canadian Consortium on Neurodegeneration in Ageing (CCNA) has established a battery of neuropsychological test which will used as secondary outcomes

  • Change in gait velocity (cm/s). [ Time Frame: baseline at 20 weeks (after interventions finalised) ]
    Gait will be assessed under single and dual-task conditions

  • Change in gait variability (%CoV). [ Time Frame: baseline at 20 weeks (after interventions finalised) ]
    Gait will be assessed under single and dual-task conditions

  • Brain structure (sMRI) [ Time Frame: baseline and at 20 weeks (after interventions finalised) ]
    Structural 3 Tesla MRI will be performed at baseline and 20 weeks in all participants who do no present contra-indication for imaging studies

  • Brain function (fMRI) [ Time Frame: baseline and at 20 weeks (after interventions finalised) ]
    Functional 3 Tesla MRI will be performed at baseline and at 20 weeks 6 in all participants who do no present contra-indication for imaging studies.

  • Changes in BDNF serum levels [ Time Frame: baseline and at 20 weeks (after interventions finalised) ]
    Changes in brain derived neurotrophic factor (BDNF) serum levels will be assessed and measured in international units

  • Combined Score of Cognition and Functionality (Pooled Index) [ Time Frame: baseline and at 20 weeks (after interventions finalised) ]
    This index will include cognitive test, gait velocity, dual task gait and the ability to perform activities of daily living. Therefore, treatments are considered successful if they slow down the progression of cognitive decline and maintain functionality and independency

  • Changes in serum levels Interleukin 1. [ Time Frame: baseline and at 20 weeks (after interventions finalised) ]
    Changes in IL-1 will be assessed in serum and measured in international units.

  • Changes in serum levels Interleukin 6. [ Time Frame: baseline and at 20 weeks (after interventions finalised) ]
    Changes in IL-6 will be assessed in serum and measured in international units.

  • Changes in serum High Sensitive C reactive protein (CRP). [ Time Frame: baseline and at 20 weeks (after interventions finalised). ]
    Serum levels of C reactive protein (CRP) 1 will be determined by standardized ELISA methods.

  • Changes in serum levels of VEGF receptor 1. [ Time Frame: baseline and at 20 weeks (after interventions finalised) ]
    Serum levels of VEGF receptor 1 will be determined by standardized ELISA methods.


Estimated Enrollment: 200
Study Start Date: July 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exercises+CognitiveTraining+Vitamin D3
Exercises will combine aerobic+resistance training. Cognitive training will be performed before exercise intervention and using using an "ad-hoc" software developed by us for tablets. Vitamin D3 (10000IU) will be provided orally three time per week for 20 weeks.
Dietary Supplement: Vitamin D3
Dose: 10000 IU, three times per week, orally.
Other Name: Cholecalciferol
Other: Exercises (E)
All participants will complete three (3) group training sessions per week (total 20 weeks), under the supervision of trainers. Each exercise session will last approximately 60 minutes and will happen after the cognitive training/control (CT cCT) session. The exercise session will be a combined aerobic and progressive strengthening exercise. Within each small group of four to eight individuals, participants follow the program tailored to their individual functioning level, with constant monitoring by the trainers. Participants are expected to attend all training sessions and research staff will strongly encourage them to do so.
Other: Cognitive Training (CT)
CT intervention will involve computer-based multimodal and multi-domain dual-task training with memory load. A custom-written program, developed for neuro-rehabilitation and used in previous research trials for cognitive and mobility outcomes will be used. Training sessions will take place in groups of four to eight participants before each of the fitness-training session for duration of 30 min max. Participants will perform a concurrent visuo-motor task (dual-task combination) composed of different sets of visual stimuli that have to be identified by tapping designated figures on an digital tablet (IOS or Android system). Participants will perform discrimination tasks involving sets of items (e.g. letters, numbers, animals, vehicles, fruits, celestial bodies).
Experimental: Exercises+CognitiveTraining+Placebo D3
Exercises will combine aerobic+resistance training. Cognitive training will be performed before exercise intervention and using using an "ad-hoc" software developed by us for tablets. Matching placebo of vitamin D3 will be provided orally three time per week for 20 weeks.
Other: Exercises (E)
All participants will complete three (3) group training sessions per week (total 20 weeks), under the supervision of trainers. Each exercise session will last approximately 60 minutes and will happen after the cognitive training/control (CT cCT) session. The exercise session will be a combined aerobic and progressive strengthening exercise. Within each small group of four to eight individuals, participants follow the program tailored to their individual functioning level, with constant monitoring by the trainers. Participants are expected to attend all training sessions and research staff will strongly encourage them to do so.
Other: Cognitive Training (CT)
CT intervention will involve computer-based multimodal and multi-domain dual-task training with memory load. A custom-written program, developed for neuro-rehabilitation and used in previous research trials for cognitive and mobility outcomes will be used. Training sessions will take place in groups of four to eight participants before each of the fitness-training session for duration of 30 min max. Participants will perform a concurrent visuo-motor task (dual-task combination) composed of different sets of visual stimuli that have to be identified by tapping designated figures on an digital tablet (IOS or Android system). Participants will perform discrimination tasks involving sets of items (e.g. letters, numbers, animals, vehicles, fruits, celestial bodies).
Other: placebo D3
matching placebo for Vitamin D3
Experimental: Exercises+Control CogTraining+Vitamin D3
Exercises will combine aerobic+resistance training. Control cognitive training will be performed before exercise intervention and will consist in computer skills training courses. Each session will consist of introductory exercises for computers and different software (e.g., Word, Excel), as well as an initiation to the Internet (search engines, websites, games, etc.). Vitamin D3 (10000IU) will be provided orally three time per week for 20 weeks
Dietary Supplement: Vitamin D3
Dose: 10000 IU, three times per week, orally.
Other Name: Cholecalciferol
Other: Exercises (E)
All participants will complete three (3) group training sessions per week (total 20 weeks), under the supervision of trainers. Each exercise session will last approximately 60 minutes and will happen after the cognitive training/control (CT cCT) session. The exercise session will be a combined aerobic and progressive strengthening exercise. Within each small group of four to eight individuals, participants follow the program tailored to their individual functioning level, with constant monitoring by the trainers. Participants are expected to attend all training sessions and research staff will strongly encourage them to do so.
Other: control cognitive training
As a control activity to ensure the same time exposure as in the interventions arms, participant in the control arm will receive a 30 min computer skills training.
Experimental: Exercises+Control CogTraining+Placebo D3
Exercises will combine aerobic+resistance training.Control cognitive training will be performed before exercise intervention and will consist in computer skills training courses. Each session will consist of introductory exercises for computers and different software (e.g., Word, Excel), as well as an initiation to the Internet (search engines, websites, games, etc. Matching placebo of vitamin D3 will be provided orally three time per week for 20 weeks.
Other: Exercises (E)
All participants will complete three (3) group training sessions per week (total 20 weeks), under the supervision of trainers. Each exercise session will last approximately 60 minutes and will happen after the cognitive training/control (CT cCT) session. The exercise session will be a combined aerobic and progressive strengthening exercise. Within each small group of four to eight individuals, participants follow the program tailored to their individual functioning level, with constant monitoring by the trainers. Participants are expected to attend all training sessions and research staff will strongly encourage them to do so.
Other: placebo D3
matching placebo for Vitamin D3
Other: control cognitive training
As a control activity to ensure the same time exposure as in the interventions arms, participant in the control arm will receive a 30 min computer skills training.
Placebo Comparator: Placebo exercise+Control Cog+Placebo D3
This will be the comparator arm with control/placebo activities.
Other: placebo D3
matching placebo for Vitamin D3
Other: control cognitive training
As a control activity to ensure the same time exposure as in the interventions arms, participant in the control arm will receive a 30 min computer skills training.
Other: Placebo exercise
As a control activity to ensure the same time exposure as in the interventions arms, participant in the control arm will receive a 60 min of a tone exercise regimen

Detailed Description:

Exercises, specifically resistance and aerobic training, have been demonstrated to improve cognitive outcomes, along with improved physical capacity and mobility. Both aerobic and resistance training trials of different duration have revealed positive results, with the most consistent findings being observed after combined interventions of 6 months to one year. Although the training benefits of progressive resistance training (PRT) have been well documented, PRT has been studied far less extensively in older adults with Mild Cognitive Impairment (MCI). Exercise training has proven to be beneficial for cognition even in vulnarable populations like in frail older adults, and those with mobility issues. The exact mechanism supporting the benefits of exercise for cognition in humans needs to be further explored, as numerous studies in animals and humans have demonstrated that aerobic exercise may have neuroprotective and neurorestorative effects. The rationale of combining aerobic and PRT as multimodal exercise intervention is supported by research that has revealed potential beneficial effects. In addition, multimodal exercise interventions have shown positive effects on muscle/lean mass, cognition and brain structure, functionality, and brain volume.

Similarly cognitive training, i.e. computer based cognitive process training, has also shown positive results in improving cognition, mobility, and postural control. Several recent systematic reviews on the topic support the benefits of cognitive training. In line with exercise training, recent research on cognitive training has also supported important improvements in brain plasticity post-intervention.

Finally, Vitamin D3 deficiency in older adults has been linked to cognitive dysfunction, dementia, and mobility decline. Besides its very well-known effects on muscle and bone physiology, several studies have shown a potential beneficial role of Vitamin D3 on cognitive function. Robustly designed trials, with longitudinal follow-up, have been recommended in older adults with MCI to investigate the comparative benefits of isolated Vitamin D3 supplementation, and combined with physical and cognitive training.

To date, the effect of adding cognitive training and/or Vitamin D3 to a multimodal progressive exercise training for improving global cognition, executive function, memory, and gait in MCI has not been assessed.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   60 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. At least 60 years of age
  2. Self-reported levels of proficiency in English (French for Montreal site only) for speaking and understanding spoken language.
  3. Able to comply with scheduled visits, treatment plan, and other trial procedures
  4. Able to ambulate at least 10 meters independently
  5. Having MCI operationalized using Albert et al. criteria as:

    • objective cognitive impairment in one of the following four cognitive domains: memory, executive function, attention, and language evaluated by the Montreal Cognitive Assessment (MoCA) test with scores ranging from 13-24/30.
    • Preserved activities of daily living on the disability scale confirmed by clinician interview
  6. Having normal or corrected to normal vision in at least one eye so that they can identify symbols and stimuli presented on a computer screen in front of them.
  7. Must be in sufficient health to participate in the study's aerobic-based exercise training program, based on medical history, vital signs, physical examination by study physicians, or written recommendation by family physician indicating one's appropriateness to participate in aerobic-based exercise training program.

Exclusion Criteria:

  1. Serious underlying disease (such as active cancer, or recent heart attack) which, in the opinion of the investigator, may preclude engagement in interventions or may interfere with the participant's ability to participate fully in the study.
  2. Diagnosis of dementia using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.
  3. Participant with uncontrolled major depression, schizophrenia, severe anxiety and substance abuse.
  4. Current parkinsonism or any neurological disorder with residual motor deficits (e.g. stroke with motor deficit), active musculo-skeletal disorders (e.g. severe osteoarthritis of lower limbs) or history of knee/hip replacement affecting gait performance at clinical evaluation.
  5. Intention to enroll in other clinical trials during the same time period
  6. Pre-existing exercise structured training program involving aerobic or resistance training in previous 6 months.
  7. Taking cognitive enhancers, neuroleptics, anticholinergics or Vitamin D3 in doses more than 1000IU/day or equivalent.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02808676


Contacts
Contact: Alanna Black, MSc, CCRP 519 685 4292 ext 42179 Alanna.Black@sjhc.london.on.ca

Locations
Canada, British Columbia
University of British Columbia Recruiting
Vancouver, British Columbia, Canada
Contact: Dr. Teresa Liu-Ambrose         
Canada, Ontario
St. Joseph's Health Care London, Parkwood Hospital Recruiting
London, Ontario, Canada, N6C5J1
Contact: Manuel Montero Odasso, MD, PhD    (519) 685-4292 ext 42179    mmontero@uwo.ca   
Principal Investigator: Manuel Montero Odasso, MD, PhD         
University of Waterloo Recruiting
Waterloo, Ontario, Canada
Contact: Dr. Laura Middleton         
Wilfrid Laurier University Recruiting
Waterloo, Ontario, Canada
Contact: Dr. Quincy Almeida         
Canada, Quebec
Concordia University, McGill University, Université de Montréal Not yet recruiting
Montréal, Quebec, Canada
Contact: Dr. Louis Bherer         
Sponsors and Collaborators
Lawson Health Research Institute
Investigators
Study Chair: Manuel M Montero-Odasso, MD, PhD Gait and Brain Lab, Lawson Health Research Institute
  More Information

Publications:
Bherer L, Erickson KI, Liu-Ambrose T. Physical exercise and brain functions in older adults. J Aging Res. 2013;2013:197326. doi: 10.1155/2013/197326. Epub 2013 Sep 17.
Liu-Ambrose T, Nagamatsu LS, Voss MW, Khan KM, Handy TC. Resistance training and functional plasticity of the aging brain: a 12-month randomized controlled trial. Neurobiol Aging. 2012 Aug;33(8):1690-8. doi: 10.1016/j.neurobiolaging.2011.05.010. Epub 2011 Jul 7.
Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci. 2003 Mar;14(2):125-30.
Langlois F, Vu TT, Chassé K, Dupuis G, Kergoat MJ, Bherer L. Benefits of physical exercise training on cognition and quality of life in frail older adults. J Gerontol B Psychol Sci Soc Sci. 2013 May;68(3):400-4. doi: 10.1093/geronb/gbs069. Epub 2012 Aug 28.
Sage MD, Almeida QJ. A positive influence of vision on motor symptoms during sensory attention focused exercise for Parkinson's disease. Mov Disord. 2010 Jan 15;25(1):64-9. doi: 10.1002/mds.22886.
Sage MD, Almeida QJ. Symptom and gait changes after sensory attention focused exercise vs aerobic training in Parkinson's disease. Mov Disord. 2009 Jun 15;24(8):1132-8. doi: 10.1002/mds.22469.
Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 2007 Sep;30(9):464-72. Epub 2007 Aug 31. Review. Erratum in: Trends Neurosci. 2007 Oct;30(10):489.
Nagamatsu LS, Handy TC, Hsu CL, Voss M, Liu-Ambrose T. Resistance training promotes cognitive and functional brain plasticity in seniors with probable mild cognitive impairment. Arch Intern Med. 2012 Apr 23;172(8):666-8. doi: 10.1001/archinternmed.2012.379. Erratum in: Arch Intern Med. 2013 Aug 12;173(15):1477.
Kueider AM, Parisi JM, Gross AL, Rebok GW. Computerized cognitive training with older adults: a systematic review. PLoS One. 2012;7(7):e40588. doi: 10.1371/journal.pone.0040588. Epub 2012 Jul 11. Review.
Reijnders J, van Heugten C, van Boxtel M. Cognitive interventions in healthy older adults and people with mild cognitive impairment: a systematic review. Ageing Res Rev. 2013 Jan;12(1):263-75. doi: 10.1016/j.arr.2012.07.003. Epub 2012 Jul 25. Review.
Ballesteros S, Prieto A, Mayas J, Toril P, Pita C, Ponce de León L, Reales JM, Waterworth J. Brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial. Front Aging Neurosci. 2014 Oct 14;6:277. doi: 10.3389/fnagi.2014.00277. eCollection 2014. Erratum in: Front Aging Neurosci. 2015;7:82.
Chapman SB, Aslan S, Spence JS, Hart JJ Jr, Bartz EK, Didehbani N, Keebler MW, Gardner CM, Strain JF, DeFina LF, Lu H. Neural mechanisms of brain plasticity with complex cognitive training in healthy seniors. Cereb Cortex. 2015 Feb;25(2):396-405. doi: 10.1093/cercor/bht234. Epub 2013 Aug 28.
Annweiler C, Montero-Odasso M, Muir SW, Beauchet O. Vitamin D and Brain Imaging in the Elderly: Should we Expect Some Lesions Specifically Related to Hypovitaminosis D? Open Neuroimag J. 2012;6:16-8. doi: 10.2174/1874440001206010016. Epub 2012 Feb 28.
Beauchet O, Annweiler C, Verghese J, Fantino B, Herrmann FR, Allali G. Biology of gait control: vitamin D involvement. Neurology. 2011 May 10;76(19):1617-22. doi: 10.1212/WNL.0b013e318219fb08. Epub 2011 Apr 6.
Annweiler C, Schott AM, Rolland Y, Blain H, Herrmann FR, Beauchet O. Dietary intake of vitamin D and cognition in older women: a large population-based study. Neurology. 2010 Nov 16;75(20):1810-6. doi: 10.1212/WNL.0b013e3181fd6352.
Montero-Odasso M, Bherer L, Studenski S, Gopaul K, Oteng-Amoako A, Woolmore-Goodwin S, Stoole P, Wells J, Doherty T, Zecevic AA, Galinsky D, Rylett RJ, Jutai J, Muir-Hunter S, Speechley M, Camicioli R. Mobility and Cognition in Seniors. Report from the 2008 Institute of Aging (CIHR) Mobility and Cognition Workshop. Can Geriatr J. 2015 Sep 30;18(3):159-67. doi: 10.5770/cgj.18.188. eCollection 2015 Sep. Review.
Annweiler C, Beauchet O, Bartha R, Hachinski V, Montero-Odasso M; WALK Team (Working group Angers-London for Knowledge). Vitamin D and caudal primary motor cortex: a magnetic resonance spectroscopy study. PLoS One. 2014 Jan 31;9(1):e87314. doi: 10.1371/journal.pone.0087314. eCollection 2014.
Montero-Odasso M, Hachinski V. Preludes to brain failure: executive dysfunction and gait disturbances. Neurol Sci. 2014 Apr;35(4):601-4. doi: 10.1007/s10072-013-1613-4. Epub 2013 Dec 24.
Montero-Odasso M, Verghese J, Beauchet O, Hausdorff JM. Gait and cognition: a complementary approach to understanding brain function and the risk of falling. J Am Geriatr Soc. 2012 Nov;60(11):2127-36. doi: 10.1111/j.1532-5415.2012.04209.x. Epub 2012 Oct 30. Review.
Skinner J, Carvalho JO, Potter GG, Thames A, Zelinski E, Crane PK, Gibbons LE; Alzheimer's Disease Neuroimaging Initiative. The Alzheimer's Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-Plus): an expansion of the ADAS-Cog to improve responsiveness in MCI. Brain Imaging Behav. 2012 Dec;6(4):489-501. doi: 10.1007/s11682-012-9166-3.
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.
Fraser SA, Li KZ, DeMont RG, Penhune VB. Effects of balance status and age on muscle activation while walking under divided attention. J Gerontol B Psychol Sci Soc Sci. 2007 May;62(3):P171-8.

Responsible Party: Manuel Montero Odasso, MD, PhD, FRCPC, Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT02808676     History of Changes
Other Study ID Numbers: 107670
First Submitted: June 6, 2016
First Posted: June 22, 2016
Last Update Posted: June 5, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Manuel Montero Odasso, Lawson Health Research Institute:
Cognitive training
Vitamin D
Exercise

Additional relevant MeSH terms:
Cognition Disorders
Mild Cognitive Impairment
Neurocognitive Disorders
Mental Disorders
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents


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