A phase 1, randomized double-blind, placebo controlled trial to evaluate safety and efficacy of epigallocatechin-3-gallate and cognitive training in adults with Fragile X syndrome

Background & aims: Despite the wide spectrum of experimental compounds tested in clinical trials, there is still no proven pharmacological treatment available for Fragile-X syndrome (FXS), since several targeted clinical trials with high expectations of success have failed to demonstrate sig...

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Detalles Bibliográficos
Autores: Torre Fornell, Rafael de la, De Sola Llopis, Susana, Xicota Vila, Laura, 1987-, Cuenca Royo, Aida Ma, 1981-, Rodriguez, Joan, Gomis González, Maria, 1988-, Hernández, Gimena, Del Hoyo Soriano, Laura, Ozaita Mintegui, Andrés, 1969-, Dierssen, Mara, TESXF Study Group, Principe, Alessandro, Espadaler, Josep María, Roca, Laia, Farré Albaladejo, Magí, Fitó Colomer, Montserrat, León Jorba, Alba, Banea, Ovideo, Maldonado, Rafael, 1961-, Busquets Garcia, Arnau, 1985-
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/37158
Acceso en línea:http://hdl.handle.net/10230/37158
http://dx.doi.org/10.1016/j.clnu.2019.02.028
Access Level:acceso abierto
Palabra clave:Fragile-X syndrome
Epigallocatechin gallate
Cognition
Functionality
Descripción
Sumario:Background & aims: Despite the wide spectrum of experimental compounds tested in clinical trials, there is still no proven pharmacological treatment available for Fragile-X syndrome (FXS), since several targeted clinical trials with high expectations of success have failed to demonstrate significant improvements. Here we tested epigallocatechin-3-gallate (EGCG) as a treatment option for ameliorating core cognitive and behavioral features in FXS. Methods: We conducted preclinical studies in Fmr1 knockout mice (Fmr1−/y) using novel object-recognition memory paradigm upon acute EGCG (10 mg/kg) administration. Furthermore we conducted a double-blind placebo-controlled phase I clinical trial (TESXF; NCT01855971). Twenty-seven subjects with FXS (18–55 years) were administered of EGCG (5–7 mg/kg/day) combined with cognitive training (CT) during 3 months with 3 months of follow-up after treatment discontinuation. Results: Preclinical studies showed an improvement in memory using the Novel Object Recognition paradigm. We found that FXS patients receiving EGCG + CT significantly improved cognition (visual episodic memory) and functional competence (ABAS II-Home Living skills) in everyday life compared to subjects receiving Placebo + CT. Conclusions: Phase 2 clinical trials in larger groups of subjects are necessary to establish the therapeutic potential of EGCG for the improvement of cognition and daily life competences in FXS.

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