Efficacy and mechanisms of device-monitored aerobic exercise for depression treatment and cognitive function improvement (DAECD trail): protocol for a randomized controlled trial

Depression is a major public health concern, yet many patients fail to achieve remission with standard pharmacotherapy or psychotherapy, and often experience relapse and persistent cognitive impairments. Enhancing treatment outcome is therefore an urgent clinical need and aerobic exercise may have great potential. However, its efficacy in depression treatment and improving cognition, as well as the underlying mechanisms remains unclear. This device-monitored aerobic exercise for depression and cognition improvement (DAECD) trail will enroll 80 patients with depression, randomly assigned (1:1) to an aerobic exercise group or a waiting control group. The intervention group will receive a device-measured aerobic exercise prescription for eight weeks, consisting of moderate-intensity sessions lasting 30 to 50 min, three times per week, alongside their routine treatment. The control group will continue with routine treatment and will initiate the same exercise intervention after the 8-week follow-up period. No additional pharmacological treatment will be initiated or adjusted during the intervention period as part of the study protocol. For those not currently on medication, the intervention will consist of aerobic exercise only. Outcomes will be assessed at baseline, mid-intervention (week 4), and post-intervention (week 8) to evaluate the efficacy of aerobic exercise. The primary outcome is the change in Hamilton Depression Rating Scale score from baseline. Secondary outcomes include cognitive function, depressive and anxiety symptoms, rumination, sleep quality, psychological resilience, safety, physical fitness, exercise capacity, and biological markers. All analyses will follow the intention-to-treat principle. A mixed-effects model will be used for continuous outcomes, and modified Poisson regression will be applied for binary outcomes. Neuroimaging, laboratory and multi-omics tests will be conducted at both baseline and post-intervention, to explore the potential mechanisms through which aerobic exercise exerts its antidepressant effects. This study aims to evaluate the efficacy of aerobic exercise in improving depression and cognition, elucidate its underlying mechanisms, and identify patient subgroups most likely to benefit. The findings may contribute to improved treatment outcomes for depression and inform the development of individualized clinical exercise prescriptions. ClincalTrials.gov NCT06594588, registered 5 Sep 2024.