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

Rafael de la Torre; Susana de Sola; Magí Farré; Laura Xicota; Aida Cuenca-Royo; Joan Rodriguez; Alba León; Klaus Langohr; María Gomis-González; Gimena Hernandez; Susanna Esteba; Laura del Hoyo; Júdit Sánchez-Gutiérrez; Maria José Cortés; Andrés Ozaita; Josep María Espadaler; Ramón Novell; Rafael Martínez-Leal; Montserrat Milá; Mara Dierssen; Alessandro Principe; Gonzalo Sánchez; Júdit Sánchez-Gutiérrez; Laia Roca; Rafasel de la Torre; Montserrat Fitó; Ovideo Banea; Maria José Cortés; Montserrat Milà; Rafael Maldonado; Arnau Busquets-Garcia; Andrés Ozaita; María Gomis-González

doi: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

Rafael de la Torre, Susana de Sola, Magí Farré, Laura Xicota, Aida Cuenca-Royo, Joan Rodriguez, Alba León, Klaus Langohr, María Gomis-González, Gimena Hernandez, Susanna Esteba, Laura del Hoyo, Júdit Sánchez-Gutiérrez, Maria José Cortés, Andrés Ozaita, Josep María Espadaler, Ramón Novell, Rafael Martínez-Leal, Montserrat Milá, Mara DierssenAlessandro Principe, Gonzalo Sánchez, Júdit Sánchez-Gutiérrez, Laia Roca, Rafasel de la Torre, Montserrat Fitó, Ovideo Banea, Maria José Cortés, Montserrat Milà, Rafael Maldonado, Arnau Busquets-Garcia, Andrés Ozaita, María Gomis-González

Research output: Contribution to journal › Article › Research

9 Citations (Scopus)

Abstract

© 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism 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.

Original language	English
Journal	Clinical Nutrition
DOIs	https://doi.org/10.1016/j.clnu.2019.02.028
Publication status	Published - 1 Jan 2019

Keywords

Cognition
Epigallocatechin gallate
Fragile-X syndrome
Functionality

Access to Document

10.1016/j.clnu.2019.02.028

Cite this

de la Torre, R., de Sola, S., Farré, M., Xicota, L., Cuenca-Royo, A., Rodriguez, J., León, A., Langohr, K., Gomis-González, M., Hernandez, G., Esteba, S., del Hoyo, L., Sánchez-Gutiérrez, J., Cortés, M. J., Ozaita, A., Espadaler, J. M., Novell, R., Martínez-Leal, R., Milá, M., ... Gomis-González, M. (2019). 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. Clinical Nutrition. https://doi.org/10.1016/j.clnu.2019.02.028

@article{197c009d009a427c8e0fc95587b07321,

title = "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",

abstract = "{\textcopyright} 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism 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.",

keywords = "Cognition, Epigallocatechin gallate, Fragile-X syndrome, Functionality",

author = "{de la Torre}, Rafael and {de Sola}, Susana and Mag{\'i} Farr{\'e} and Laura Xicota and Aida Cuenca-Royo and Joan Rodriguez and Alba Le{\'o}n and Klaus Langohr and Mar{\'i}a Gomis-Gonz{\'a}lez and Gimena Hernandez and Susanna Esteba and {del Hoyo}, Laura and J{\'u}dit S{\'a}nchez-Guti{\'e}rrez and Cort{\'e}s, {Maria Jos{\'e}} and Andr{\'e}s Ozaita and Espadaler, {Josep Mar{\'i}a} and Ram{\'o}n Novell and Rafael Mart{\'i}nez-Leal and Montserrat Mil{\'a} and Mara Dierssen and Alessandro Principe and Gonzalo S{\'a}nchez and J{\'u}dit S{\'a}nchez-Guti{\'e}rrez and Laia Roca and {de la Torre}, Rafasel and Montserrat Fit{\'o} and Ovideo Banea and Cort{\'e}s, {Maria Jos{\'e}} and Montserrat Mil{\`a} and Rafael Maldonado and Arnau Busquets-Garcia and Andr{\'e}s Ozaita and Mar{\'i}a Gomis-Gonz{\'a}lez",

year = "2019",

month = jan,

day = "1",

doi = "10.1016/j.clnu.2019.02.028",

language = "English",

journal = "Clinical Nutrition",

issn = "0261-5614",

publisher = "Churchill Livingstone",

}

de la Torre, R, de Sola, S, Farré, M, Xicota, L, Cuenca-Royo, A, Rodriguez, J, León, A, Langohr, K, Gomis-González, M, Hernandez, G, Esteba, S, del Hoyo, L, Sánchez-Gutiérrez, J, Cortés, MJ, Ozaita, A, Espadaler, JM, Novell, R, Martínez-Leal, R, Milá, M, Dierssen, M, Principe, A, Sánchez, G, Sánchez-Gutiérrez, J, Roca, L, de la Torre, R, Fitó, M, Banea, O, Cortés, MJ, Milà, M, Maldonado, R, Busquets-Garcia, A, Ozaita, A & Gomis-González, M 2019, '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', Clinical Nutrition. https://doi.org/10.1016/j.clnu.2019.02.028

TY - JOUR

T1 - 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

AU - de la Torre, Rafael

AU - de Sola, Susana

AU - Farré, Magí

AU - Xicota, Laura

AU - Cuenca-Royo, Aida

AU - Rodriguez, Joan

AU - León, Alba

AU - Langohr, Klaus

AU - Gomis-González, María

AU - Hernandez, Gimena

AU - Esteba, Susanna

AU - del Hoyo, Laura

AU - Sánchez-Gutiérrez, Júdit

AU - Cortés, Maria José

AU - Ozaita, Andrés

AU - Espadaler, Josep María

AU - Novell, Ramón

AU - Martínez-Leal, Rafael

AU - Milá, Montserrat

AU - Dierssen, Mara

AU - Principe, Alessandro

AU - Sánchez, Gonzalo

AU - Sánchez-Gutiérrez, Júdit

AU - Roca, Laia

AU - de la Torre, Rafasel

AU - Fitó, Montserrat

AU - Banea, Ovideo

AU - Cortés, Maria José

AU - Milà, Montserrat

AU - Maldonado, Rafael

AU - Busquets-Garcia, Arnau

AU - Ozaita, Andrés

AU - Gomis-González, María

PY - 2019/1/1

Y1 - 2019/1/1

N2 - © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism 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.

AB - © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism 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.

KW - Cognition

KW - Epigallocatechin gallate

KW - Fragile-X syndrome

KW - Functionality

U2 - 10.1016/j.clnu.2019.02.028

DO - 10.1016/j.clnu.2019.02.028

M3 - Article

C2 - 30962103

SN - 0261-5614

JO - Clinical Nutrition

JF - Clinical Nutrition

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this