A randomised, placebo-controlled, triple-blind clinical trial to investigate the efficacy of Ginkgo biloba extract EGb 761® in cognitive impairment associated with post COVID-19 syndrome—the EGb COCOS protocol

Background Cognitive impairment is frequent in post-COVID-19 syndrome (PCS). The understanding of the pathogenesis is still limited. Key factors such as neuroinflammation, neurovascular dysfunction, and disruption of cellular energy metabolism have been identified. There are no evidence-based treatments targeting the pathologic mechanisms of cognitive impairment associated with PCS available to date. Thus, treatment is directed towards symptom relief. EGb 761 ® , a dry extract from the leaves of Ginkgo biloba has anti-neuroinflammatory properties, improves microcirculation and neuronal mitochondrial function. Clinical efficacy in the treatment of cognitive impairment has been demonstrated. It is therefore reasonable to assume that the extract might be beneficial for use in cognitive impairment associated with PCS. Case series of patients with PCS reported significant improvement in cognitive function within 6 months of treatment. The EGb 761 ® Post COVID Cognitive Impairment Study (EGb COCOS) aims to establish whether EGb 761 ® is an effective treatment for cognitive impairment in PCS. Methods In this prospective, multicentre, randomised, placebo-controlled, triple-blind trial, treatment effects and safety of EGb 761 ® in patients with cognitive impairment associated with PCS will be investigated. Eligible patients aged ≥18 years with a history of probable or confirmed SARS-CoV-2 infection, diagnosis of PCS with cognitive symptoms that have been present for at least 2 months, objective cognitive impairment, and mild-to-moderate anxiety or depressive symptoms will be enrolled. Participants ( n = 400 planned) will be randomised to oral, 12-week treatment with EGb 761 ® (240 mg) or matching placebo once daily. The effect of EGb 761 ® will be assessed on cognitive, neuropsychiatric, neurosensory, and functional outcomes. The analysis will be exploratory in nature, since generally accepted and validated primary endpoints have not been established. For safety, the incidence of adverse events (AEs) and serious AEs will be recorded. Discussion The results of this trial will show for the first time whether EGb 761 ® is an effective treatment for cognitive impairment in PCS. Clinical trial registration https://euclinicaltrials.eu/ctis-public/view/2024-517199-39-00?lang=en , Identifier CTIS2024-517199-39-00.