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
Xavier Morato, Marta Marquié, Juan Pablo Tartari, Asunción Lafuente, María Eugenia Sáez, Laia Montoliu-Gaya, Hanna Huber, Montserrat Alegret, Sara Jofresa, Mar Buendía, Ana Pancho, Nuria Aguilera, Marta Ibarria, Susana Diego, Rosario Cuevas, Laia Cañada, Alba Pérez-Cordón, Angela Sanabria, Itziar De Rojas, Amanda Cano, Adelina Orellana, Laura Montrreal, Maitee Rosende-Roca, Liliana Vargas, Ana Espinosa, Gemma Ortega, Raúl Núñez-Llaves, Marta Martínez-Lucas, Yahveth Cantero-Fortiz, Emilio Alarcón-Martín, Miren Gurruchaga, Lluís Tárraga, Sergi Valero, Pilar Sanz-Cartagena, Santos Mañes, Henrik Zetterberg, Agustín Ruiz, Mercè BoadaBackground
Neuroinflammation 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.
Objective
This 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).
Methods
We 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 Aβ 40 , Aβ 42 , Aβ 42/40 ratio, GFAP, NfL, and pTau231 were measured in plasma. Clinical, neurological, and neuropsychological assessments were performed at each visit.
Results
EGb 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.
Conclusions
EGb 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,