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. Issue 2 (February 2020)

• Record Type: Journal Article
• Authors: Cuenca-Royo, Aida; Principe, Alessandro; Hernandez, Gimena; Sánchez, Gonzalo; Rodriguez, Joan; Espadaler, Josep María; Sánchez-Gutiérrez, Judit; Langohr, Klaus; Roca, Laia; del Hoyo, Laura; Xicota, Laura; Farré, Magí; Dierssen, Mara; de la Torre, Rafasel; Fitó, Montserrat; de Sola, Susana; León, Alba; Banea, Ovideo; Novell, Ramón; Esteba, Susanna; Martínez-Leal, Rafael; Cortés, María José; Milà, Montserrat; Maldonado, Rafael; Busquets-Garcia, Arnau; Ozaita, Andres; Gomis-González, Maria; de la Torre, Rafael; de Sola, Susana; Farré, Magí; Xicota, Laura; Cuenca-Royo, Aida; Rodriguez, Joan; León, Alba; Langohr, Klaus; Gomis-González, María; Hernandez, Gimena; Esteba, Susanna; del Hoyo, Laura; Sánchez-Gutiérrez, Júdit; Cortés, Maria José; Ozaita, Andrés; Espadaler, Josep María; Novell, Ramón; Martínez-Leal, Rafael; Milá, Montserrat; Dierssen, Mara;
• Is Part Of: Clinical nutrition. Volume 39:Issue 2(2020)
• Page Start: 378
• Page End: 387
• Publication Date: 2020-02
• Subjects: Fragile-X syndrome -- Epigallocatechin gallate -- Cognition -- Functionality; Critically ill -- Nutrition -- Periodicals; Diet therapy -- Periodicals; Parenteral feeding -- Periodicals; Enteral feeding -- Periodicals; Enteral Nutrition -- Periodicals; Parenteral Nutrition -- Periodicals; Metabolism -- Periodicals; Diétothérapie -- Périodiques; Alimentation parentérale -- Périodiques; Alimentation entérale -- Périodiques; Nutrition -- Périodiques; Diet therapy; Enteral feeding; Nutrition; Parenteral feeding; Electronic journals; Periodicals; Electronic journals; 615.854
• DOI: 10.1016/j.clnu.2019.02.028
• Languages: English
• ISSNs: 0261-5614

Abstract

Summary: 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. Graphical abstract: Image 1