SYNERGIC TRIAL (SYNchronizing Exercises, Remedies in Gait and Cognition) a multi-Centre randomized controlled double blind trial to improve gait and cognition in mild cognitive impairment

Abstract

Background: Physical exercise, cognitive training, and vitamin D are low cost interventions that have the potential to enhance cognitive function and mobility in older adults, especially in pre-dementia states such as Mild Cognitive Impairment (MCI). Aerobic and progressive resistance exercises have benefits to cognitive performance, though evidence is somewhat inconsistent. We postulate that combined aerobic exercise (AE) and progressive resistance training (RT) (combined exercise) will have a better effect on cognition than a balance and toning control (BAT) intervention in older adults with MCI. We also expect that adding cognitive training and vitamin D supplementation to the combined exercise, as a multimodal intervention, will have synergistic efficacy.

Methods: The SYNERGIC trial (SYNchronizing Exercises, Remedies in GaIt and Cognition) is a multi-site, double-blinded, five-arm, controlled trial that assesses the potential synergic effect of combined AE and RT on cognition and mobility, with and without cognitive training and vitamin D supplementation in older adults with MCI. Two-hundred participants with MCI aged 60 to 85 years old will be randomized to one of five arms, four of which include combined exercise plus combinations of dual-task cognitive training (real vs. sham) and vitamin D supplementation (3 × 10,000 IU/wk. vs. placebo) in a quasi-factorial design, and one arm which receives all control interventions. The primary outcome measure is the ADAS-Cog (13 and plus modalities) measured at baseline and at 6 months of follow-up. Secondary outcomes include neuroimaging, neuro-cognitive performance, gait and mobility performance, and serum biomarkers of inflammation (C reactive protein and interleukin 6), neuroplasticity (brain-derived neurotropic factor), endothelial markers (vascular endothelial growth factor 1), and vitamin D serum levels.

Discussion: The SYNERGIC Trial will establish the efficacy and feasibility of a multimodal intervention to improve cognitive performance and mobility outcomes in MCI. These interventions may contribute to new approaches to stabilize and reverse cognitive-mobility decline in older individuals with MCI.

Trial registration: Identifier: NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676 .

Keywords: Cognition; Cognitive training; Dementia; Exercise; Gait; MCI; Vitamin D.

Conflict of interest statement

Ethics approval and consent to participate

This study is conducted in compliance with International Conference on Harmonization Good Clinical Practice (ICH-GCP) and all applicable regulatory requirements. Sponsor site obtained approval of the Research Ethics Board at the University of Western Ontario (REB# 107670), the Lawson Health Research Institute’s Clinical Research Impact Committee (R-15-038), and Health Canada (HC file - HC6–24-c195918 / HC protocol #201619) prior to initiating study-related activities. Each intervention site has also obtained local ethical approval. Written consent to participate was obtained when participants signed the letter of information and consent. Capacity to consent was determined on the basis of direct observation of the participant and/or from information obtained from their family. Participants in this study do not have a degree of cognitive impairment (such as advanced dementia) that would prevent them from understanding the information given and appreciating the consequences of their decision.

Competing interests

The authors declare they have no competing interests.

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Figures

Fig. 1

Consortium flowchart for the SYNERGIC Trial

Fig. 2

Schematic Timeline of the SYNERGIC Trial. a Recruitment of participants will be an on-going process with individuals being assigned to groups as they are enrolled. Recruitment is expected to be finished between 12 to 18 months. b Baseline assessments (T0) will be completed within one-week of participant starting the specific intervention/placebo. Participants will return to the clinic six months (c) after starting the specific intervention/placebo to complete the post intervention assessment (T6). After six months participants will return to the clinic again (T12) at which time their final assessment will be completed (d). 9 months after their first baseline assessment (T0) i.e. 3 months post-intervention, there will be a follow-up phone call

Fig. 3

Conceptual model for individual and synergistic effects of planned interventions in the SYNERGIC Trial