P3‐029: EFFICACY AND SAFETY OF OXIRACETAM IN PATIENTS WITH VASCULAR COGNITIVE IMPAIRMENT (OVERCOME): DESIGN AND RATIONALE FOR A MULTICENTER, RANDOMIZED, DOUBLE‐BLINDED, PLACEBO‐CONTROLLED, PARALLEL‐DESIGN, PHASE IV CLINICAL TRIAL

Exercise enhances cognitive function and increases the size of hippocampus in ischemic stroke patients. Medial septal neurons are the sources of cholinergic and GABAergic afferents to the hippocampus and involve in the upregulation of brain derived neurotrophic factor in response to exercise. Oxiracetam activates acetylcholine utilization in the hippocampus. Various clinical trials showed that its effect was modest in patients with vascular cognitive impairment. This study aims to investigate the effect of Oxiracetam on cognitive impairment after stroke and to explore whether this effect is modified by exercise. The OVeRCOME is a phase 4, multicenter, randomized, double-blind, placebo-controlled, parallel design trial. This study will enroll at-risk patients who complain of subjective cognitive decline after 3 months from index stroke with one of the followings; over 70 years of age, recurrent stroke, atrial fibrillation, diabetes, moderate to severe white matter hyperintensities, global cortical atrophy, or medial temporal atrophy. Subjects are randomly assigned to receive either 800 mg Oxiracetam for 36 weeks or placebo twice a day and are requested to maintain the levels of exercise during the study. Degrees of exercise are assessed using wrist actigraphy at the 4, 12, 24, and 36 weeks after randomization. The co-primary endpoints are changes in mini-mental state examination and clinical dementia rating sum of boxes at 36 weeks versus baseline. The secondary endpoint is changes in various measures of the 60-minitute Korean version of vascular cognitive impairment harmonization standards, Euro QoL, patient's global assessment, and neural network attributes. Neural network measures include modularity, clustering coefficient, and global efficiency, which are assessed using resting-state functional MRI and diffusion tensor imaging. A total of 506 patients will be enrolled, and twenty centers will be expected to participate in the study. The expected date of the last enrollment is April 2020. OVeRCOME is a promising study for assessing the effect modification of exercise on the effect of nootropics on cognitive impairment after stroke. It is expected to validate the utility of a functional network analysis in a clinical trial setting and to help understand the mechanism of cognitive changes after stroke.