A single-center open-label, randomized, parallel-group controlled clinical trial on the long-term effect of the treatment with EGb 761 in blood markers of inflammation and neurodegeneration in patients with mild cognitive impairment: ACE-2020-EGb 761.
Abstract
BackgroundNeuroinflammation plays a central role in Alzheimer's disease (AD) pathology and other dementias. EGb 761, a standardized Ginkgo biloba extract, has shown potential anti-inflammatory and neuroprotective properties.ObjectiveThis study evaluated the effects of EGb 761 on plasma proteins related to inflammation and neurodegeneration, cognitive performance, and core AD biomarkers in individuals with mild cognitive impairment (MCI).MethodsWe conducted a 12-month randomized, controlled, open-label clinical trial with a 12-month extension phase in 100 patients with MCI recruited at a single center. During the first 12 months, participants were randomly assigned to EGb 761 or no treatment. In the extension phase, all participants received EGb 761 for an additional 12 months. Plasma samples were collected at baseline and at 6-month intervals throughout both phases. Inflammatory and neurological proteomic profiles were assessed using the Olink Inflammation and Neurology panels. AD biomarkers including Aβ40, Aβ42, Aβ42/40 ratio, GFAP, NfL, and pTau231 were measured in plasma. Clinical, neurological, and neuropsychological assessments were performed at each visit.ResultsEGb 761 was associated with nominally significant longitudinal decreases in 15 plasma proteins linked to innate immunity and axon guidance, replicated in the delayed-start group.ConclusionsEGb 761 exposure is associated with longitudinal modulation of serum markers associated with systemic inflammation and neurodegeneration in MCI. Larger placebo-controlled biomarker-driven trials are warranted to confirm whether this translates into clinically meaningful neuroprotection.Trial registration:Registro Español de estudios clínicos (REec) 2020-003776-41, ClinicalTrials.gov NCT05594355, https://clinicaltrials.gov/study/NCT05594355.