Clinical trial NCT05375513: SYNERGIC-2 Trial (SYNchronizing, Exercises and Remedies to GaIn Cognition@home)
Official title: A Home-based Personalized Multidomain RCT from the Canadian Therapeutic Platform for Multidomain Interventions to Prevent Dementia (CAN-THUMBS UP)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Mild Cognitive Impairment
Keywords: Dementia
Mild Cognitive Impairment
Virtual Interventions
Geriatric Medicine
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2022-05-16
Enrollment: 275
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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 will be administered virtually through online video conferencing platform systems (WeBex or Zoom Healthcare©). 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
Primary purpose: PREVENTION

Brief 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. 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.

Eligibility criteria: Inclusion Criteria

1. Ages 60-85 years.
2. Having mild cognitive impairment (MCI) defined as meeting all of the following:

   1. Presence of subjective memory complaints from the participant and/or informant.
   2. Objective impairment on cognitive tests independent of outcome measures.†
   3. 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.
   4. 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
3. Have ≥1 additional 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).
4. 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).
5. Self-reported levels of proficiency in English for speaking and understanding spoken and written language.
6. Have normal/corrected to normal vision in at least one eye to identify stimuli on computer/tablet screen.
7. 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.
8. Able to comply with virtual visits, treatment plan, and trial-related activities.
9. Ability to participate in the study's exercise training as determined by the Get Active Questionnaire (GAQ).

Exclusion Criteria

1. Having a diagnosis of dementia (based on DSM-IV criteria).
2. 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.
3. 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.
4. Regular use of Benzodiazepine or neuroleptic drugs that may interfere with the participants ability to participate in the assessments and interventions.
5. Recent (in the past 12 months) and/or current substance or alcohol abuse.
6. 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.
7. Intention to enroll in other interventional clinical trials during same time.

Primary outcomes:
measure: Change in global cognition assessed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) with 13 items (ADASCog-13)
timeFrame: baseline and at 48 weeks (after interventions finalized)
Secondary outcomes:
measure: Change in Anthropometric Measures
timeFrame: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
measure: Change in Cardiovascular Risk Factors, Aging, and Incidence of Dementia
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in the CCNA Gait Assessments results-Walking performance
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in Clinical Dementia Rating scores
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in Digit Symbol Modalities Test - Oral Version (mental processing speed)
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in Eating Pattern Self-Assessment
timeFrame: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
measure: Changes in Fall Occurrence
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in Generalized Anxiety Disorder (GAD-7)
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Change in Geriatric Depression Scale (GDS-30)
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Change in Health Utility Index (HUI-3)
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in Health Resource Utilization Questionnaire (HRUQ)
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in Insomnia Severity Index
timeFrame: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
measure: Changes in International Physical Activity Questionnaire scores
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in the Lawton-Brody Instrumental Activities of Daily Living (IADL) scale
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in the Mediterranean Diet Assessment
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in global cognitive function using Montreal Cognitive Assessment(MoCA)
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in the Oral Trail Making Test - Attention Shifting capabilities/executive functions using
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in Quality of Life Questionnaire (SF-36)
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in Rey Auditory Verbal Learning Test (RAVLT)-Episodic memory
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in the Cognitive Expectancies Questionnaire
timeFrame: Baseline and follow-up at 12 months
measure: Changes in sleep pattern
timeFrame: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
measure: Changes in physical activity in the elderly
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in behavior
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in BHPro questionnaires
timeFrame: Baseline, month 3, mid-intervention at 6 months, month 9, and follow-up at 12 months
measure: Changes in EEG
timeFrame: Baseline and follow-up at 12 months
measure: Identification of APO-E variants, a planned panel of 31 single nucleotide polymorphisms (SNPs), and untargeted metabolomics
timeFrame: Baseline and follow-up at 12 months
measure: Changes in Resource Use Inventory Q7 & Q8 (RUI Q7 &Q8)
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in 60s Chair Standing Test
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in The Activities-specific Balance Confidence Scale (ABC) questionnaire
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Changes in The Short Physical Performance Battery (SPPB)
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Other outcomes:
measure: Recruitment Rate
timeFrame: Throughout study completion - avg. 12 months/participant
measure: Retention Rate
timeFrame: Throughout study completion - avg. 12 months/participant
measure: Assessment Tolerability
timeFrame: Baseline
measure: Adverse Events
timeFrame: Throughout study completion - avg. 12 months/participant
measure: Data Loss
timeFrame: Throughout study completion - avg. 12 months/participant
measure: Sex of Participant
timeFrame: Baseline
measure: Age of Participant
timeFrame: Baseline
measure: Medications Taken by Participant
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
measure: Chronic Diseases of Participant
timeFrame: Baseline, mid-intervention at 6 months, and follow-up at 12 months
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Fredericton
country: Canada
facility: University of New Brunswick
state: New Brunswick
city: London
country: Canada
facility: St. Joseph's Health Care London, Parkwood Hospital
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa
state: Ontario
city: Toronto
country: Canada
facility: Baycrest Academy for Research and Education
state: Ontario
city: Waterloo
country: Canada
facility: University of Waterloo
state: Ontario
city: Montréal
country: Canada
facility: Concordia University
state: Quebec
Study officials:
affiliation: St. Joseph's Health Care London, Parkwood Hospital
name: Manuel Montero-Odasso, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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