Mild Cognitive ImpairmentSYN2NCT05375513
SYNERGIC-2 Trial (SYNchronizing, Exercises and Remedies to GaIn Cognition@Home)
A study testing PMI@Home and Brain Health Pro in people with Mild Cognitive Impairment, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 8 sites in Canada.
Trial summary
In Canada, 1,700,000 adults are at risk of dementia, half of them with MCI,representing one of the largest groups at risk for an incurable disease. Epidemiological evidence suggests up to 40% of dementia cases might be preventable by targeting modifiable lifestyle and cardiovascular factors. Read more about this study
- Who is it for?
- Ages 60 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment
- What is being tested?
- PMI@Home and Brain Health Pro
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 250 participants
- Where
- 8 sitesCanada
- Study dates
- 5 Jun 2023to 30 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Ages 60-85 years.
- Having mild cognitive impairment (MCI) defined as meeting all of the following:
- Presence of subjective memory complaints from the participant and/or informant.
- Objective impairment on cognitive tests independent of outcome measures.†
- Preserved activities of daily living assessed (>14/23 in Lawton-Brody IADL score). For the study, impairment of daily living will be assessed based on cognitive abilities, not physical abilities.
- Absence of clinical dementia per DSM-IV criteria †Objective cognitive impairment is operationalized as: Montreal Cognitive Assessment (MoCA) total score between 16 and 25 (inclusive), and/or RAVLT delayed recall ≤6, and /or Clinical Dementia Rating Scale (CDR) =0.5
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- Have at least 1 dementia risk factors targeted by our intervention as follows: low physical activity (less than 150 minutes of moderate-to-vigorous-intensity physical activity per week, as per GAQ), poor diet (14-item Mediterranean Diet Assessment (MDA-14) score ≤7), insomnia or subthreshold insomnia ( Insomnia Severity Index (ISI) score >7), and vascular-metabolic risk (Cardiovascular Risk Factors Aging and Incidence of Dementia (CAIDE) score ≥6 and/or diabetes (type I or II) and/or obesity (BMI≥30) and/or diagnosis of high blood pressure (hypertension) and/or smoking).
- Have access to a home computer/laptop/tablet with home internet (have regular access to email) and ability to use technology (able to send and receive emails and join video conferences).
- Self-reported levels of proficiency in English for speaking and understanding spoken and written language.
- Have normal/corrected to normal vision in at least one eye to identify stimuli on computer/tablet screen.
- Have normal to corrected hearing ability, in order for the participant to engage in digital/virtual communication. Research personnel will determine and assess the hearing ability as per participant's performance.
- Able to comply with virtual visits, treatment plan, and trial-related activities.
- Ability to participate in the study's exercise training as determined by the Get Active Questionnaire (GAQ).
Who cannot join
- Having a diagnosis of dementia (based on DSM-IV criteria).
- Underlying severe disease that precludes engagement with interventions, including presence of psychiatric diagnoses (i.e., major depression (Geriatric Depression Scale (GDS-30) >19), schizophrenia, severe anxiety, neurological disorder with severe motor deficits, such as current parkinsonism or any neurological disorder with residual severe motor deficits (i.e., stroke with motor deficit), or presence of unstable (non-controlled e.g., symptoms that suggest instability or no treatment for their condition) chronic disease such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) that may preclude the participant from engaging properly with the trial interventions, or advanced-stage active cancer that at the study physician's discretion will prevent them from participating.
- Having had surgery within the last 2 months or having an upcoming planned surgery in the next 12 months that could interfere with the participant's vision, hearing, mobility, or any other abilities to participate in the study.
- Regular use of Benzodiazepine or neuroleptic drugs that may interfere with the participants ability to participate in the assessments and interventions.
- Recent (in the past 12 months) and/or current substance or alcohol abuse.
- Having had a transmural myocardial infarction (severe heart attack) within six months prior to enrollment in the clinical trial that according to the study physician may preclude physical activity performance.
- Intention to enroll in other interventional clinical trials during same time.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Canada8 sites, 8 recruiting
- Recruiting
University of Alberta
Edmonton, Alberta, T6G 2G3
Dr. Richard Camicioli
- Recruiting
University of New Brunswick
Fredericton, New Brunswick
Dr. Chris McGibbon
- Recruiting
St. Joseph's Health Care London, Parkwood Hospital
London, Ontario, N6C5J1
Manuel Montero Odasso, MD, PhD, (519) 685-4292 ext. 42179, mmontero@uwo.ca
Manuel Montero Odasso, MD, PhD
- Recruiting
Concordia University
Montreal, Quebec
Dr. Karen Li
- Recruiting
University of Ottawa
Ottawa, Ontario
Dr. Sarah Fraser
- Recruiting
Baycrest Academy for Research and Education
Toronto, Ontario
Dr. Howard Chertkow
- Recruiting
University of British Columbia
Vancouver, British Columbia
- Recruiting
University of Waterloo
Waterloo, Ontario
Dr. Laura Middleton
About this study
Official title: A Home-based Personalized Multidomain RCT From the Canadian Therapeutic Platform for Multidomain Interventions to Prevent Dementia (CAN-THUMBS UP)
In Canada, 1,700,000 adults are at risk of dementia, half of them with MCI,representing one of the largest groups at risk for an incurable disease. Epidemiological evidence suggests up to 40% of dementia cases might be preventable by targeting modifiable lifestyle and cardiovascular factors. Given that current treatments cannot modify the disease, prevention is critical. SYNERGIC-2 offers a "personalized multidomain intervention" that combines physical and cognitive training, sleep, diet, and vascular-metabolic interventions in individuals with MCI to synergistically enhance their overall brain health including cognition and contributes to maintaining their independence. Importantly, interventions will be provided at home using an existing virtual platform reducing delivery complexity and expanding the accessibility to a wider population, thus decreasing potential inequities. Improving older adults' brain health and achieving even a modest two-year dementia incidence delay will have a projected saving of $218 Billion in Canada's healthcare system over 30 years.
Read the detailed description
Epidemiological evidence suggests up to 40% of potential dementia cases might be preventable by targeting modifiable lifestyle and cardiovascular factors; given that current treatments cannot modify the disease, prevention is a critical aspect. SYNERGIC-2 is the first large Canadian clinical trial using a 12-month home-based personalized multidomain lifestyle intervention to improve cognition in 550 older adults with Mild Cognitive Impairment (MCI), a pre-dementia state. These personalized at-home interventions target 5 domains with tailored physical exercise, cognitive training, diet recommendations, sleep interventions, and vascular risk factor management and are all delivered using a digital platform. Specifically, SYNERGIC-2 will be conducted with participants in their homes using video-conference meetings to test participants and to coach them 1-on-1 through the interventions on a web-based digital platform. The effect of these combined interventions on cognition will be compared to an online-educational program Brain Health PRO (BHPro). Both interventions are part of CAN-THUMBS UP, the interventional platform of the CCNA related to Canada Dementia Research Strategy; and constitutes Canada's contribution to the World-Wide-FINGERS Network. Importantly, these interventions have been selected because there is evidence that they synergistically enhance overall brain health including cognition and contributes to maintaining independence for individuals at risk for developing dementia.
- Conditions
- Mild Cognitive Impairment
- Being tested
- PMI@Home, Brain Health Pro
- Keywords
- Dementia, Mild Cognitive Impairment, Virtual Interventions, Geriatric Medicine
- Medical subject headings
- Cognitive Dysfunction, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PMI@HomeOther
Personalized multidomain interventional program by combining tailored lifestyle interventions that targets 5 domains: physical activity, cognition, diet, sleep, and vascular risk factors. These interventions are tailored based on participants' baseline profile and progress in intensity following the principles of personalized medicine. All aspects of the PMI@home will be delivered remotely, at participants' homes, using a "digital platform" with scheduled bi-weekly 1-to1 coaching sessions. Delivery of interventions and assessments are centralized with 5 trained staff at the sponsor site (London) to assure logistics, standardization, and quality control.
Brain Health ProOther
Online Modules:
- Motivation, Self-Efficacy, Positive Health, Environment and Genetic risk
- Physical Activity
- Cognitively Stimulating Activities
- Diet
- Sleep
- Social and Psychological Health
- Vascular health
- Vision and Hearing
- Lifestyle Risk Impact Surveys
- Goal Setting
| Study group | Role | What they receive |
|---|---|---|
| SYNERGIC 2 | Active comparator | Personalized multidomain coached 1-to-1 interventions at home (PMI@Home) including:
1. Physical Exercise
2. Cognitive Training
3. Diet
4. Sleep
5. Vascular Risk Factors Control Receives: Other: PMI@Home |
| Brain Health PRO (BHPro) | Placebo comparator | Brain Health PRO (BHPROBHPRO) is an independent, educational program with content also related to:
1. Physical Exercise
2. Cognitive Training
3. Diet
4. Sleep
5. Vascular Risk Factors
6. Social engagement Receives: Other: Brain Health Pro |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in global cognition assessed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) with 13 items (ADASCog-13)
Global cognition will be assessed using the cognitive section of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) with 13 items (ADASCog-13). This scale consists of 13 brief cognitive tests assessing attention, memory, language, executive function, praxis, orientation, and instrumental activities of daily living. The ADAS-Cog has been a significant outcome measure in numerous trials with MCI and AD to measure changes in cognitive performance in populations with cognitive impairment, it score ranges from 0 to 84, with higher scores indicating worse cognitive performance.
Measured: baseline and at 48 weeks (after interventions finalized)
Secondary outcomes (30)
Change in Anthropometric Measures
Measurements of weight and hip/waist circumference will be done at home and self-reported by the participant. This can be used to characterize participant's body dimension and determine body mass index as kg/m^2 which can be used to estimate whether participants have obesity. A BMI greater than 30 is the cut off for obesity. Changes in waist circumference may also indicate visceral fat and cardiovascular risk.
Measured: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
Change in Cardiovascular Risk Factors, Aging, and Incidence of Dementia
The Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) is a short questionnaire assessing midlife vascular risk for dementia, with scores ranging from 0 to 15 (higher scores suggesting higher risk) and has cut-off score of 5 for high risk.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in the CCNA Gait Assessments results-Walking performance
The CCNA gait assessment includes preferred and fast pace gait, and dual-task gait that comprises walking while performing three cognitively demanding tasks: counting backwards by ones, counting backwards by sevens, and naming animals. Participants will be asked to walk on a designated walking path(4 meters) in sight of camera
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Clinical Dementia Rating scores
The Clinical Dementia Rating (CDR) scale is a validated scale (0-3) used in longitudinal Alzheimer's Disease (AD) research to characterize the impact of cognitive decline on global function performance applicable to AD and related dementias. Information is obtained through a semi-structured interview of the patient and a reliable informant or collateral source (e.g. family member). A score of ) indicate no cognitive impairment; 0.5 for Mild cognitive impairment; 1 for early dementia; 2 for mild severe dementia; 3 for severe dementia
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Digit Symbol Modalities Test - Oral Version (mental processing speed)
The Digit Symbol Modalities Test is a 90-second, timed task that asks participants to orally match geometric figures with specific numbers according to a defined key (specifying which symbols are assigned to which numbers) that is provided at the top of the stimulus page. The oral Digit Symbol Modalities Test measures processing speed capabilities. The total number of numbers correctly matched with symbols is the final score for this test ranging from 0-110 correct numbers sequentially spoken.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Eating Pattern Self-Assessment
The Eating Pattern Self-Assessment (EPSA) is a 12-item questionnaire assessing participants' dietary intake profiles over the past 12 months. No score provided
Measured: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
Changes in Fall Occurrence
The monthly falls calendar that will be sent to help track any participant falls. Participants are being asked to complete this calendar on a daily basis in order to help investigators better track whether or not they have fallen since last intervention. A fall is defined as any unintentional event in which a participant falls to the ground or onto an object (e.g., a chair) no caused by a syncope or loss of consciousness. Total number of falls and consequences of falls is provided.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Generalized Anxiety Disorder (GAD-7)
A questionnaire to score the frequency the participant experiences anxiety symptoms in the past 7 days with higher scores indicating worse anxiety symptoms. Score ranges from 0-21.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Change in Geriatric Depression Scale (GDS-30)
A questionnaire to establish a participant's experience with depressive symptoms with higher score indicating more severe depressive symptoms. Score ranges from 0-30.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Change in Health Utility Index (HUI-3)
The HUI-3 provides descriptive health profile measures on a generic scale with higher scores indicating better quality of life and global functionality. HUI also provides single-attribute scores of morbidities for the following attributes; vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain. Score ranges from one 1 to 6 or 1 to 5 depending on the domain; and sum of all domains could range from 8 to 45.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Health Resource Utilization Questionnaire (HRUQ)
The HRUQ provides an overall assessment of a participants utilization of health-related resource use and costs for elderly adults with and without mild cognitive impairment.There is no scoring for the HRUQ
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Insomnia Severity Index
The Insomnia Severity Index (ISI) is a 7-item questionnaire assessing sleep onset, sleep maintenance, sleep satisfaction, and sleep problems.
Measured: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
Changes in International Physical Activity Questionnaire scores
Modified for the elderly people, assesses older adults' level of physical activity, with a simple 7-item questionnaire. Scoring ranges from low, moderate and high.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in the Lawton-Brody Instrumental Activities of Daily Living (IADL) scale
Measures participant's ability to engage in instrumental activities of daily living via questionnaire assessing the ability to independently perform activities such as using the telephone, shopping, preparing meals, chores, household activities, managing prescriptions and medications, and managing personal finances. Score ranges from 0-23.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in the Mediterranean Diet Assessment
A 14-item questionnaire to help evaluate a participants Mediterranean ingredients in their diet. Score ranges from 0-14.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in global cognitive function using Montreal Cognitive Assessment(MoCA)
The MoCA is a brief screening instrument designed to detect global cognitive dysfunction. It assesses a range of different cognitive domains, including attention, executive functions, memory, language, visuo-constructional skills, abstract thinking, and orientation. Score ranges from 0-30.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in the Oral Trail Making Test - Attention Shifting capabilities/executive functions using
The Oral Trail Making Test (TMT) A \& B is a two-part test that assesses attention speed, and mental flexibility and has been widely used in clinical settings for assessing deficits in attention and executive functioning. Score from part A ranges from 0-180; part B from 0-300 seconds. Longer times mean worse performance in the test.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Quality of Life Questionnaire (SF-36)
The Short-Form Quality of Life Questionnaire (SF-36) is a 36-item questionnaire assessing quality of life, with scores ranging from 0 to 100 and higher scores indicating better quality of life.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Rey Auditory Verbal Learning Test (RAVLT)-Episodic memory
The Rey Auditory Verbal Learning Test (RAVLT) assesses episodic memory, in which the participant is presented with 15 words in five presentations or trials, after which they are asked to recall the words (immediately and after a delay). Score ranges from 0 to 15 words recalled.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in the Cognitive Expectancies Questionnaire
It is a version developed by the CCNA to measures participant's expectancies about the cognitive benefits of the intervention. Score ranges from 1 to 88. This questionnaire measures the participant's perception about the interventions. The questionnaire outcome is not related to participant's cognition, but participant's subjective perception about the interventions.
Measured: Baseline and follow-up at 12 months
Changes in sleep pattern
The Sleep Diary is self-administered of 10-days of sleep patterns to assess sleep quality and total of sleep time. It also helps to identify possible sleep disruptions that may affect sleep quality and identify certain habits that may explain sleeping issues.
Measured: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
Changes in physical activity in the elderly
The Wrist (AX3) Accelerometer is used to detect movement, vibrations, and orientation changes to assess physical activity trends in older population.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in behavior
This questionnaire asks about eleven health behaviors, to be rated on a 0 (low) to 10 (high) scale. Prior research has demonstrated that a 1-point change on these 0 to 10 items is clinically meaningful.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in BHPro questionnaires
These questionnaires ask about cognition (6-item questionnaire), vascular health (4-item questionnaire), and social and psychological health (8-item questionnaire).
- BHPro Questionnaire - Cognition: This questionnaire asks about participant's engagement in activities such as reading, crafting, and instrument playing. It does not provide any quantitative range score.
- BHPro Questionnaire - Social and Psychological Health: This questionnaire asks about participant's emotions and mood. It does not provide any quantitative range score.
- BHPro Questionnaire - Vascular Health: This questionnaire asks about participant's updated medical history. It does not provide any quantitative range score.
Measured: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
Changes in EEG
Participants will use the MUSE-S EEG Headband for 3 consecutive nights. The MUSE S Headband is a commercially available consumer headband that has 7 sensors, 2 on the forehead, 2 behind the ears, plus 3 reference sensors, to detect and measure EEG signals when sleeping.
Measured: Baseline and follow-up at 12 months
Identification of APO-E variants, a planned panel of 31 single nucleotide polymorphisms (SNPs), and untargeted metabolomics
Participants will use the DNA-Genotek, which is a self-administered saliva collection kit to analyze saliva sample for possible identification of APO-E variants, a planned panel of 31 single nucleotide polymorphisms (SNPs), and untargeted metabolomics.
Measured: Baseline and follow-up at 12 months
Changes in Resource Use Inventory Q7 & Q8 (RUI Q7 &Q8)
Questions 7 and 8 from the Resource Use Inventory (RUI)28 questionnaire assess health-related resource use for caregivers. This instrument has been used for tracking resource use and costs in cognitively intact older adults, as well as with Alzheimer disease (AD). This is a self-report questionnaire investigates if participants received any help while preforming daily living tasks e.g., bathing, brushing, and getting the phone. It does not provide any quantitative range score.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in 60s Chair Standing Test
Participants will be performing the one-minute chair stand test while being assessed via video conferencing by a research team member to evaluate mobility.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in The Activities-specific Balance Confidence Scale (ABC) questionnaire
The ABC questionnaire consists of 16 questions where the participants rate their confidence that they will not lose their balance or become unsteady while performing different activities. They need to rate 16 different activities from 0 to 100, 0 being not confident at all, and 100 being completely confident on their abilities to perform the activity.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in The Short Physical Performance Battery (SPPB)
The SPPB is an objective assessment tool for evaluating lower extremity functioning in older adults. Score ranges from 0 to 12. 0 being frail (disabled), and 12 being no mobility disability issues.
Measured: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2022
- Study start5 Jun 2023
- Primary completion30 Nov 2027 (estimated)
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (49)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The SYNERGIC-2 Trial is a single-blind, two-arm, randomized controlled trial (RCT) evaluating the cognitive effect of personalized multidomain interventions that target physical exercise, cognitive training, sleep, diet, and vascular risk factors. The SYNERGIC-2 Trial is administered virtually through online video conferencing platform systems (MicrosoftTeams, Zoom, etc.). Figure 1 illustrates the trial design. The trial adheres to the Consolidated Standards of Reporting Trials (CONSORT) guidelines for conducting and reporting clinical trials, as extended to non-pharmacological interventions. A total of 550 participants with MCI aged 60-85 will be enrolled and randomized into one of two arms, with 275 participants in each arm. This sample size assumes a conservative 10% drop out yielding a final sample of 500 for analyses, enough to detect a significant effect size of 0.15. To achieve a significant effect size of 0.16, 400 participants are needed for the final analyses.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Manuel Montero-Odasso, MD, PhD, Principal investigator, St. Joseph's Health Care London, Parkwood Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05375513
- Sponsor's protocol ID
- 3948
- Acronym
- SYN2
- Status last verified
- Sep 2026
- First submitted
- 21 Apr 2022
- Last updated
- 21 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Delis DC, Kramer JH, Kaplan E, Holdnack J. Reliability and validity of the Delis-Kaplan Executive Function System: an update. J Int Neuropsychol Soc. 2004 Mar;10(2):301-3. doi: 10.1017/S1355617704102191. No abstract available.
PubMed 15012851Schmidt M. Rey auditory verbal learning test: A handbook. Los Angeles, CA: Western Psychological Services.; 1996.
Esther Strauss OS. Trail Making Tests. New York: Oxford University Press; 1998.
Koblinsky ND, Anderson ND, Ajwani F, Parrott MD, Dawson D, Marzolini S, Oh P, MacIntosh B, Middleton L, Ferland G, Greenwood CE. Feasibility and preliminary efficacy of the LEAD trial: a cluster randomized controlled lifestyle intervention to improve hippocampal volume in older adults at-risk for dementia. Pilot Feasibility Stud. 2022 Feb 9;8(1):37. doi: 10.1186/s40814-022-00977-6.
PubMed 35139918Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092-7. doi: 10.1001/archinte.166.10.1092.
PubMed 16717171DOPPELT JE, WALLACE WL. Standardization of the Wechsler adult intelligence scale for older persons. J Abnorm Psychol. 1955 Sep;51(2):312-30. doi: 10.1037/h0044391. No abstract available.
PubMed 13263050Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.
PubMed 15817019Peters R, Booth A, Rockwood K, Peters J, D'Este C, Anstey KJ. Combining modifiable risk factors and risk of dementia: a systematic review and meta-analysis. BMJ Open. 2019 Jan 25;9(1):e022846. doi: 10.1136/bmjopen-2018-022846.
PubMed 30782689Bennett DA, Schneider JA, Buchman AS, Barnes LL, Boyle PA, Wilson RS. Overview and findings from the rush Memory and Aging Project. Curr Alzheimer Res. 2012 Jul;9(6):646-63. doi: 10.2174/156720512801322663.
PubMed 22471867Falck RS, Davis JC, Best JR, Li LC, Chan PCY, Wyrough AB, Landry GJ, Liu-Ambrose T. Buying time: a proof-of-concept randomized controlled trial to improve sleep quality and cognitive function among older adults with mild cognitive impairment. Trials. 2018 Aug 17;19(1):445. doi: 10.1186/s13063-018-2837-7.
PubMed 30119694Carney CE, Buysse DJ, Ancoli-Israel S, Edinger JD, Krystal AD, Lichstein KL, Morin CM. The consensus sleep diary: standardizing prospective sleep self-monitoring. Sleep. 2012 Feb 1;35(2):287-302. doi: 10.5665/sleep.1642.
PubMed 22294820Csizmadi I, Kahle L, Ullman R, Dawe U, Zimmerman TP, Friedenreich CM, Bryant H, Subar AF. Adaptation and evaluation of the National Cancer Institute's Diet History Questionnaire and nutrient database for Canadian populations. Public Health Nutr. 2007 Jan;10(1):88-96. doi: 10.1017/S1368980007184287.
PubMed 17212847Sala-Vila A, Valls-Pedret C, Rajaram S, Coll-Padros N, Cofan M, Serra-Mir M, Perez-Heras AM, Roth I, Freitas-Simoes TM, Domenech M, Calvo C, Lopez-Illamola A, Bitok E, Buxton NK, Huey L, Arechiga A, Oda K, Lee GJ, Corella D, Vaque-Alcazar L, Sala-Llonch R, Bartres-Faz D, Sabate J, Ros E. Effect of a 2-year diet intervention with walnuts on cognitive decline. The Walnuts And Healthy Aging (WAHA) study: a randomized controlled trial. Am J Clin Nutr. 2020 Mar 1;111(3):590-600. doi: 10.1093/ajcn/nqz328.
PubMed 31912155Loughrey DG, Lavecchia S, Brennan S, Lawlor BA, Kelly ME. The Impact of the Mediterranean Diet on the Cognitive Functioning of Healthy Older Adults: A Systematic Review and Meta-Analysis. Adv Nutr. 2017 Jul 14;8(4):571-586. doi: 10.3945/an.117.015495. Print 2017 Jul.
PubMed 28710144Borm GF, Fransen J, Lemmens WA. A simple sample size formula for analysis of covariance in randomized clinical trials. J Clin Epidemiol. 2007 Dec;60(12):1234-8. doi: 10.1016/j.jclinepi.2007.02.006. Epub 2007 Jun 6.
PubMed 17998077
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Home-based Personalized Multidomain RCT From the Canadian Therapeutic Platform for Multidomain Interventions to Prevent Dementia (CAN-THUMBS UP)
- ClinicalTrials.gov ID
- NCT05375513
- Acronym / sponsor ID
- SYN2 / 3948
- Conditions
- Mild Cognitive Impairment
- Keywords
- Dementia, Mild Cognitive Impairment, Virtual Interventions, Geriatric Medicine
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- 5 Jun 2023 (actual)
- Primary completion
- 30 Nov 2027 (estimated)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 16 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In Canada, 1,700,000 adults are at risk of dementia, half of them with MCI,representing one of the largest groups at risk for an incurable disease. Epidemiological evidence suggests up to 40% of dementia cases might be preventable by targeting modifiable lifestyle and cardiovascular factors. Given that current treatments cannot modify the disease, prevention is critical. SYNERGIC-2 offers a "personalized multidomain intervention" that combines physical and cognitive training, sleep, diet, and vascular-metabolic interventions in individuals with MCI to synergistically enhance their overall brain health including cognition and contributes to maintaining their independence. Importantly, interventions will be provided at home using an existing virtual platform reducing delivery complexity and expanding the accessibility to a wider population, thus decreasing potential inequities. Improving older adults' brain health and achieving even a modest two-year dementia incidence delay will have a projected saving of $218 Billion in Canada's healthcare system over 30 years.
Detailed description
Epidemiological evidence suggests up to 40% of potential dementia cases might be preventable by targeting modifiable lifestyle and cardiovascular factors; given that current treatments cannot modify the disease, prevention is a critical aspect. SYNERGIC-2 is the first large Canadian clinical trial using a 12-month home-based personalized multidomain lifestyle intervention to improve cognition in 550 older adults with Mild Cognitive Impairment (MCI), a pre-dementia state. These personalized at-home interventions target 5 domains with tailored physical exercise, cognitive training, diet recommendations, sleep interventions, and vascular risk factor management and are all delivered using a digital platform. Specifically, SYNERGIC-2 will be conducted with participants in their homes using video-conference meetings to test participants and to coach them 1-on-1 through the interventions on a web-based digital platform. The effect of these combined interventions on cognition will be compared to an online-educational program Brain Health PRO (BHPro). Both interventions are part of CAN-THUMBS UP, the interventional platform of the CCNA related to Canada Dementia Research Strategy; and constitutes Canada's contribution to the World-Wide-FINGERS Network. Importantly, these interventions have been selected because there is evidence that they synergistically enhance overall brain health including cognition and contributes to maintaining independence for individuals at risk for developing dementia.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The SYNERGIC-2 Trial is a single-blind, two-arm, randomized controlled trial (RCT) evaluating the cognitive effect of personalized multidomain interventions that target physical exercise, cognitive training, sleep, diet, and vascular risk factors. The SYNERGIC-2 Trial is administered virtually through online video conferencing platform systems (MicrosoftTeams, Zoom, etc.). Figure 1 illustrates the trial design. The trial adheres to the Consolidated Standards of Reporting Trials (CONSORT) guidelines for conducting and reporting clinical trials, as extended to non-pharmacological interventions. A total of 550 participants with MCI aged 60-85 will be enrolled and randomized into one of two arms, with 275 participants in each arm. This sample size assumes a conservative 10% drop out yielding a final sample of 500 for analyses, enough to detect a significant effect size of 0.15. To achieve a significant effect size of 0.16, 400 participants are needed for the final analyses.
| Arm | Type | Receives |
|---|---|---|
| SYNERGIC 2 | Active comparator | Other: PMI@HomePersonalized multidomain coached 1-to-1 interventions at home (PMI@Home) including: 1. Physical Exercise 2. Cognitive Training 3. Diet 4. Sleep 5. Vascular Risk Factors Control |
| Brain Health PRO (BHPro) | Placebo comparator | Other: Brain Health ProBrain Health PRO (BHPROBHPRO) is an independent, educational program with content also related to: 1. Physical Exercise 2. Cognitive Training 3. Diet 4. Sleep 5. Vascular Risk Factors 6. Social engagement |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Ages 60-85 years.
- Having mild cognitive impairment (MCI) defined as meeting all of the following:
- Have at least 1 dementia risk factors targeted by our intervention as follows: low physical activity (less than 150 minutes of moderate-to-vigorous-intensity physical activity per week, as per GAQ), poor diet (14-item Mediterranean Diet Assessment (MDA-14) score ≤7), insomnia or subthreshold insomnia ( Insomnia Severity Index (ISI) score >7), and vascular-metabolic risk (Cardiovascular Risk Factors Aging and Incidence of Dementia (CAIDE) score ≥6 and/or diabetes (type I or II) and/or obesity (BMI≥30) and/or diagnosis of high blood pressure (hypertension) and/or smoking).
- Have access to a home computer/laptop/tablet with home internet (have regular access to email) and ability to use technology (able to send and receive emails and join video conferences).
- Self-reported levels of proficiency in English for speaking and understanding spoken and written language.
Key exclusion criteria (7 listed)
- Having a diagnosis of dementia (based on DSM-IV criteria).
- Underlying severe disease that precludes engagement with interventions, including presence of psychiatric diagnoses (i.e., major depression (Geriatric Depression Scale (GDS-30) >19), schizophrenia, severe anxiety, neurological disorder with severe motor deficits, such as current parkinsonism or any neurological disorder with residual severe motor deficits (i.e., stroke with motor deficit), or presence of unstable (non-controlled e.g., symptoms that suggest instability or no treatment for their condition) chronic disease such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) that may preclude the participant from engaging properly with the trial interventions, or advanced-stage active cancer that at the study physician's discretion will prevent them from participating.
- Having had surgery within the last 2 months or having an upcoming planned surgery in the next 12 months that could interfere with the participant's vision, hearing, mobility, or any other abilities to participate in the study.
- Regular use of Benzodiazepine or neuroleptic drugs that may interfere with the participants ability to participate in the assessments and interventions.
- Recent (in the past 12 months) and/or current substance or alcohol abuse.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PMI@HomePersonalized multidomain interventional program by combining tailored lifestyle interventions that targets 5 domains: physical activity, cognition, diet, sleep, and vascular risk factors. These interventions are tailored based on participants' baseline profile and progress in intensity following the principles of personalized medicine. All aspects of the PMI@home will be delivered remotely, at participants' homes, using a "digital platform" with scheduled bi-weekly 1-to1 coaching sessions. Delivery of interventions and assessments are centralized with 5 trained staff at the sponsor site (London) to assure logistics, standardization, and quality control. | Other | SYNERGIC 2 |
| Brain Health ProOnline Modules: * Motivation, Self-Efficacy, Positive Health, Environment and Genetic risk * Physical Activity * Cognitively Stimulating Activities * Diet * Sleep * Social and Psychological Health * Vascular health * Vision and Hearing * Lifestyle Risk Impact Surveys * Goal Setting | Other | Brain Health PRO (BHPro) |
Primary outcome
Change in global cognition assessed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) with 13 items (ADASCog-13)
Time frame: baseline and at 48 weeks (after interventions finalized)
Global cognition will be assessed using the cognitive section of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) with 13 items (ADASCog-13). This scale consists of 13 brief cognitive tests assessing attention, memory, language, executive function, praxis, orientation, and instrumental activities of daily living. The ADAS-Cog has been a significant outcome measure in numerous trials with MCI and AD to measure changes in cognitive performance in populations with cognitive impairment, it score ranges from 0 to 84, with higher scores indicating worse cognitive performance.
30 secondary outcomes
Change in Anthropometric Measures
Time frame: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
Change in Cardiovascular Risk Factors, Aging, and Incidence of Dementia
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in the CCNA Gait Assessments results-Walking performance
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Clinical Dementia Rating scores
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Digit Symbol Modalities Test - Oral Version (mental processing speed)
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Eating Pattern Self-Assessment
Time frame: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
Changes in Fall Occurrence
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Generalized Anxiety Disorder (GAD-7)
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Change in Geriatric Depression Scale (GDS-30)
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Change in Health Utility Index (HUI-3)
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Health Resource Utilization Questionnaire (HRUQ)
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Insomnia Severity Index
Time frame: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
Changes in International Physical Activity Questionnaire scores
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in the Lawton-Brody Instrumental Activities of Daily Living (IADL) scale
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in the Mediterranean Diet Assessment
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in global cognitive function using Montreal Cognitive Assessment(MoCA)
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in the Oral Trail Making Test - Attention Shifting capabilities/executive functions using
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Quality of Life Questionnaire (SF-36)
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in Rey Auditory Verbal Learning Test (RAVLT)-Episodic memory
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in the Cognitive Expectancies Questionnaire
Time frame: Baseline and follow-up at 12 months
Changes in sleep pattern
Time frame: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
Changes in physical activity in the elderly
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in behavior
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in BHPro questionnaires
Time frame: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
Changes in EEG
Time frame: Baseline and follow-up at 12 months
Identification of APO-E variants, a planned panel of 31 single nucleotide polymorphisms (SNPs), and untargeted metabolomics
Time frame: Baseline and follow-up at 12 months
Changes in Resource Use Inventory Q7 & Q8 (RUI Q7 &Q8)
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in 60s Chair Standing Test
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in The Activities-specific Balance Confidence Scale (ABC) questionnaire
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Changes in The Short Physical Performance Battery (SPPB)
Time frame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
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- Background: PubMed 16717171Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092-7. doi: 10.1001/archinte.166.10.1092.
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- Background: PubMed 15817019Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.
- Background: PubMed 30782689Peters R, Booth A, Rockwood K, Peters J, D'Este C, Anstey KJ. Combining modifiable risk factors and risk of dementia: a systematic review and meta-analysis. BMJ Open. 2019 Jan 25;9(1):e022846. doi: 10.1136/bmjopen-2018-022846.
- Background: PubMed 22471867Bennett DA, Schneider JA, Buchman AS, Barnes LL, Boyle PA, Wilson RS. Overview and findings from the rush Memory and Aging Project. Curr Alzheimer Res. 2012 Jul;9(6):646-63. doi: 10.2174/156720512801322663.
- Background: PubMed 30119694Falck RS, Davis JC, Best JR, Li LC, Chan PCY, Wyrough AB, Landry GJ, Liu-Ambrose T. Buying time: a proof-of-concept randomized controlled trial to improve sleep quality and cognitive function among older adults with mild cognitive impairment. Trials. 2018 Aug 17;19(1):445. doi: 10.1186/s13063-018-2837-7.
- Background: PubMed 22294820Carney CE, Buysse DJ, Ancoli-Israel S, Edinger JD, Krystal AD, Lichstein KL, Morin CM. The consensus sleep diary: standardizing prospective sleep self-monitoring. Sleep. 2012 Feb 1;35(2):287-302. doi: 10.5665/sleep.1642.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Manuel Montero-Odasso, MD, PhD principal investigator
St. Joseph's Health Care London, Parkwood Hospital
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PMI@Home and Brain Health Pro in people with Mild Cognitive Impairment, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 8 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Diana Amaris (519-646-6100 ext. 45629, Diana.Amaris@sjhc.london.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in global cognition assessed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) with 13 items (ADASCog-13) (time frame: baseline and at 48 weeks (after interventions finalized)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05375513, which also lists 49 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.