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

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-

doi:http://dx.doi.org/10.1016/j.clnu.2019.02.028

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

Citation

de la Torre R, de Sola S, Farré M, Xicota L, Cuenca-Royo A, Rodriguez J et al. 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. Clin Nutr. 2020;39(2):378-87. DOI 10.1016/j.clnu.2019.02.028

Abstract

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.