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)

Overview

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.

Interventions

• Other PMI@Home
  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. Deliv
• Other Brain Health Pro
  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

Primary outcome measures

• 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)]

Secondary outcome measures (12)

• 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]

Eligibility criteria

Inclusion criteria

• 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
• 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).
• 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).

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Canada · 8 centers

• University of Alberta — Edmonton
• University of British Columbia — Vancouver
• University of New Brunswick — Fredericton
• St. Joseph's Health Care London, Parkwood Hospital — London
• University of Ottawa — Ottawa
• Baycrest Academy for Research and Education — Toronto
• University of Waterloo — Waterloo
• Concordia University — Montreal

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. PMID 15012851
• Schmidt 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. PMID 35139918
• Spitzer 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. PMID 16717171
• DOPPELT 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. PMID 13263050
• Nasreddine 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. PMID 15817019
• Peters 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. PMID 30782689

Identifiers

NCT: NCT05375513 · 3948

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗