Home-Based Multifaceted Intervention for Mild Cognitive Impairment

(SYN2 Trial)

Recruiting at 7 trial locations

Overseen By Dr. Laura Middleton

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Must not be taking: Benzodiazepines, Neuroleptics

Disqualifiers: Dementia, Major depression, Schizophrenia, Severe anxiety, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 12 months

275 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude people who regularly use certain drugs like Benzodiazepines or neuroleptics. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment SYNERGIC-2 for mild cognitive impairment?

Research shows that home-based cognitive training and multimodal interventions, which include exercises and cognitive activities, can help improve cognitive function in people with mild cognitive impairment. Studies like the MAXCOG trial and the COCOA trial suggest that personalized, home-based interventions can be beneficial for cognitive health. ^{1 2 3 4 5}

Is the home-based multifaceted intervention for mild cognitive impairment safe for humans?

The home-based virtual reality exercise program for people with mild cognitive impairment was found to be safe, with no major adverse events reported during a 6-week study. ^{6 7 8 9 10}

How is the SYNERGIC-2 treatment for mild cognitive impairment unique?

The SYNERGIC-2 treatment is unique because it combines home-based exercises and remedies specifically designed to improve cognition, which is different from other treatments that may focus on either exercise or cognitive training alone. This multifaceted approach aims to synchronize various activities to enhance cognitive function at home. ^{2 6 8 11 12}

Research Team

Manuel Montero-Odasso, MD, PhD

Principal Investigator

St. Joseph's Health Care London, Parkwood Hospital

Eligibility Criteria

The SYNERGIC-2 trial is for adults aged 60-85 in Canada with Mild Cognitive Impairment (MCI) who have memory complaints, some objective cognitive impairment but no dementia. Participants should be able to use email and a computer, speak and understand English, have good vision and hearing, engage in virtual visits, and perform daily activities independently. They must also have at least two additional risk factors like low physical activity or poor diet.

Inclusion Criteria

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), 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 ≥2 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 (Insomnia Severity Index (ISI) score ≥15), 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, 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)

I am between 60 and 85 years old.

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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 12-month home-based personalized multidomain lifestyle intervention targeting physical exercise, cognitive training, diet, sleep, and vascular risk factors.

12 months

Regular virtual visits for coaching and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Follow-up assessments at 12 months

Treatment Details

Interventions

• SYNchronizing, Exercises and Remedies to GaIn Cognition@Home

Trial Overview This trial tests a 'personalized multidomain intervention' called PMI@Home combined with Brain Health Pro software. It aims to improve brain health by addressing lifestyle factors such as exercise, sleep, diet, and vascular-metabolic issues through home-based virtual platforms to potentially delay the onset of dementia.

Participant Groups

Group I: SYNERGIC 2 Active Control 1 Intervention

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

Group II: Brain Health PRO (BHPro) Placebo Group 1 Intervention

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

SYNchronizing, Exercises and Remedies to GaIn Cognition@Home is already approved in Canada for the following indications:

Approved in Canada as SYNERGIC-2 Trial for:

• Prevention of dementia in individuals with Mild Cognitive Impairment (MCI)

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Findings from Research

In a study involving 57 patients with amnestic mild cognitive impairment (aMCI), a 12-week home-based cognitive intervention (HCI) significantly improved cognitive function, particularly in verbal fluency as measured by the Controlled Oral Word Association Test (COWAT).

Despite the cognitive improvements, the study did not find significant changes in brain metabolism as measured by 18F-FDG PET imaging, suggesting that while HCI can enhance cognitive abilities, it may not immediately affect underlying brain metabolic processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of 12-week home-based cognitive training on cognitive function and brain metabolism in patients with amnestic mild cognitive impairment. Park, J., Kim, SE., Kim, EJ., et al.[2022]

The MAXCOG intervention, a home-based cognitive rehabilitation program, significantly improved goal performance and satisfaction for clients with mild cognitive impairment (MCI) or early dementia, as shown in a randomized controlled trial with 55 client-supporter dyads.

Out of the participants, 25 dyads completed the MAXCOG sessions, demonstrating that personalized interventions can effectively address individual goals, leading to better outcomes compared to standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MAXCOG-Maximizing Cognition: A Randomized Controlled Trial of the Efficacy of Goal-Oriented Cognitive Rehabilitation for People with Mild Cognitive Impairment and Early Alzheimer Disease. Regan, B., Wells, Y., Farrow, M., et al.[2022]

The COCOA trial is a two-arm randomized controlled trial designed to test the effectiveness of personalized multimodal lifestyle interventions, including diet, cognitive training, and exercise, in altering the cognitive decline trajectory in individuals with Alzheimer's disease and related dementias over a 2-year period.

The trial aims to demonstrate that data-driven remote coaching can enhance compliance and personalize interventions, potentially leading to improved cognitive outcomes, particularly for those in the early stages of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Coaching for Cognition in Alzheimer's (COCOA) trial: Study design. Roach, JC., Hara, J., Fridman, D., et al.[2023]

A new cognitive composite measure, ADAS-Cog-Exec, was developed for the EXERT trial, which is a 12-month exercise intervention study aimed at individuals with mild cognitive impairment (MCI).

This composite measure showed higher sensitivity to detect changes in cognitive function over 12 months compared to the traditional ADAS-Cog13 total score, making it a more effective primary outcome for assessing the impact of exercise on cognitive decline in MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a novel cognitive composite outcome to assess therapeutic effects of exercise in the EXERT trial for adults with MCI: The ADAS-Cog-Exec. Jacobs, DM., Thomas, RG., Salmon, DP., et al.[2022]

A pilot study involving 47 participants with mild cognitive impairment showed that intensive, computer-based cognitive training improved neuropsychological assessment scores by 0.36 standard deviations, although this was not statistically significant compared to the control group.

The study suggests that while the cognitive training may have specific benefits for verbal learning and memory, further research with larger sample sizes is needed to confirm these effects and explore their potential domain-specific impacts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computer-based cognitive training for mild cognitive impairment: results from a pilot randomized, controlled trial. Barnes, DE., Yaffe, K., Belfor, N., et al.[2022]

A 12-week SMARTfit dual-task training program for older adults with mild cognitive impairment led to significant improvements in cognitive tests (Trail-Making Test and Stroop Test) and physical performance (Short Physical Performance Battery).

Participants in the program reported a positive training experience, suggesting that community-based interventions like SMARTfit could be beneficial for preserving cognitive and physical function in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SMARTfit Dual-Task Exercise Improves Cognition and Physical Function in Older Adults With Mild Cognitive Impairment: Results of a Community-Based Pilot Study. Jhaveri, S., Romanyk, M., Glatt, R., et al.[2023]

Nootropics, particularly L-a-glyceryl-phosphoryl-ethanolamine (L-a GPE), show promise in preserving cognitive function in patients with mild cognitive impairment (MCI) by targeting brain pathways related to neurotransmitters and promoting neuronal health.

L-a GPE acts as a precursor for phospholipids and an acetylcholine donor, potentially countering age-related cognitive decline by enhancing cognitive reserve and protecting against neuronal loss and oxidative stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive function modulation during aging: a focus on L-alpha-GPE. Biggio, G., Di Fazio, I., Martini, C.[2022]

Home-based virtual reality (VR) exercise is safe and feasible for individuals with mild cognitive impairment, with participants completing 99% of the prescribed sessions over 6 weeks without major adverse events.

While most participants enjoyed the VR program and reported physical benefits, no significant changes were observed in physical or cognitive outcomes after the 6-week intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Home-Based Nonimmersive Virtual Reality to Encourage Physical and Cognitive Exercise in People With Mild Cognitive Impairment: A Feasibility Study. Sheehy, L., Sveistrup, H., Knoefel, F., et al.[2022]

This study aims to evaluate the efficacy of a standardized herbal formula, Sailuotong (SLT), over 12 weeks in improving cognition in older adults with mild cognitive impairment (MCI), a condition that increases the risk of dementia.

The trial will also investigate SLT's mechanisms of action through various measures, including EEG and brain blood flow, while ensuring safety in a cohort of 80 participants, highlighting the need for new treatments for MCI as current pharmaceutical options have shown poor results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for a randomised, double-blind, placebo-controlled 12-week pilot phase II trial of Sailuotong (SLT) for cognitive function in older adults with mild cognitive impairment. Steiner, GZ., Bensoussan, A., Liu, J., et al.[2019]

In a 24-week trial involving 324 patients with amnestic mild cognitive impairment (aMCI), herbal therapy significantly improved cognitive function, showing a mean decrease of 4.23 points on the ADAS-cog scale, comparable to the effects of donepezil.

The herbal therapy was associated with fewer adverse events compared to donepezil, indicating it is a safer and well-tolerated treatment option for patients with aMCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of an Herbal Therapy in Patients with Amnestic Mild Cognitive Impairment: A 24-Week Randomized Phase III Trial. Tian, J., Shi, J., Li, T., et al.[2020]

A 12-week sport stacking intervention showed significant improvements in cognitive function, particularly in immediate recall memory, for individuals with mild Alzheimer's disease (AD) and mild cognitive impairment (MCI), with a notable effect size (Cohen d = 0.66).

The intervention also led to increased levels of plasma brain-derived neurotrophic factor (BDNF), suggesting a potential mechanism for the cognitive benefits observed, especially in participants with MCI who experienced the most significant improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Sport Stacking on Cognition in Patients With Mild Alzheimer's Disease and MCI: Preliminary Findings of Randomized Controlled Trial. Yang, Z., Yang, J., Yu, DSF., et al.[2023]

In a clinical trial involving 175 older adults with mild cognitive impairment (MCI), a multidomain intervention combining aerobic-resistance exercises and computerized cognitive training significantly improved cognitive function compared to a control group, suggesting potential benefits in delaying dementia onset.

Vitamin D supplementation did not show any significant effect on cognitive improvement, indicating that the benefits observed were primarily due to the exercise and cognitive training components of the intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Exercise Alone or Combined With Cognitive Training and Vitamin D Supplementation to Improve Cognition in Adults With Mild Cognitive Impairment: A Randomized Clinical Trial. Montero-Odasso, M., Zou, G., Speechley, M., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Effect of 12-week home-based cognitive training on cognitive function and brain metabolism in patients with amnestic mild cognitive impairment. [2022]

2. England pubmed.ncbi.nlm.nih.gov

MAXCOG-Maximizing Cognition: A Randomized Controlled Trial of the Efficacy of Goal-Oriented Cognitive Rehabilitation for People with Mild Cognitive Impairment and Early Alzheimer Disease. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The Coaching for Cognition in Alzheimer's (COCOA) trial: Study design. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Development of a novel cognitive composite outcome to assess therapeutic effects of exercise in the EXERT trial for adults with MCI: The ADAS-Cog-Exec. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Computer-based cognitive training for mild cognitive impairment: results from a pilot randomized, controlled trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

SMARTfit Dual-Task Exercise Improves Cognition and Physical Function in Older Adults With Mild Cognitive Impairment: Results of a Community-Based Pilot Study. [2023]

7. Italy pubmed.ncbi.nlm.nih.gov

Cognitive function modulation during aging: a focus on L-alpha-GPE. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

The Use of Home-Based Nonimmersive Virtual Reality to Encourage Physical and Cognitive Exercise in People With Mild Cognitive Impairment: A Feasibility Study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Study protocol for a randomised, double-blind, placebo-controlled 12-week pilot phase II trial of Sailuotong (SLT) for cognitive function in older adults with mild cognitive impairment. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of an Herbal Therapy in Patients with Amnestic Mild Cognitive Impairment: A 24-Week Randomized Phase III Trial. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Effects of Sport Stacking on Cognition in Patients With Mild Alzheimer's Disease and MCI: Preliminary Findings of Randomized Controlled Trial. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Effects of Exercise Alone or Combined With Cognitive Training and Vitamin D Supplementation to Improve Cognition in Adults With Mild Cognitive Impairment: A Randomized Clinical Trial. [2023]