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

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.

• Authors: 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, TESXF Study Group
• Journal: Clinical nutrition (Edinburgh, Scotland) (Clin Nutr) Vol. 39 Issue 2 Pg. 378-387 (02 2020) ISSN: 1532-1983 [Electronic] England
• PMID: 30962103 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Chemical References

• Neuroprotective Agents
• Catechin
• epigallocatechin gallate

Topics

• Adult
• Animals
• Catechin (analogs & derivatives, therapeutic use)
• Cognition Disorders (complications, drug therapy, therapy)
• Disease Models, Animal
• Double-Blind Method
• Female
• Fragile X Syndrome (complications, drug therapy, therapy)
• Humans
• Male
• Mice
• Mice, Knockout
• Middle Aged
• Neuroprotective Agents (therapeutic use)
• Treatment Outcome
• Young Adult