"Using Epigallocatechin Gallate (EGCG) and Cognitive Training to Modulate Cognitive Performance in Patients With Fragile X Syndrome" (TESFX)

Parc de Salut Mar

Status and phase: Completed; Phase 2

Conditions: Fragile X Syndrome

Treatments: Dietary Supplement: Placebo; Dietary Supplement: EGCG; Other: Cognitive training

Study type: Interventional

Funder types: Other

Identifiers

NCT01855971

TESXF

Details and patient eligibility

About

Fragile X syndrome (FXS) presents alterations in synaptic plasticity that produce intellectual disability. can produce improvement. Estrogens (targeting Estrogen Receptors beta (ER-β) can act as neuroprotective agents, promoting synaptic plasticity and neurite outgrowth, and health benefits derived from flavonoids, as the flavonol epigallocatechin gallate (EGCG), phytoestrogens of natural origin are partially explained by their interaction with membrane ER. Selective ER-β flavonoids are thus good candidates for their therapeutic evaluation in intellectual disabilities. EGCG also targets central intracellular transduction signals altered in FXS and improves memory recognition in a FXS animal model(adenosine triphosphate (ATP)-inhibitor of phosphatidylinositol 3-kinase (PI3K)and mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK1/2). This study targets the synaptic plasticity alterations that underlie the learning and memory impairment but also the computational disability in FXS. The hypothesis is that EGCG can act by favoring the physiological processes involved in cognition.

Enrollment: 44 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Molecular diagnosis of Fragile X syndrome (FXS)
• Males and females aged 12 to 60 years.
• Study participants must understand and accept experimental procedures and assent to participate in the study signing an informed consent.
• Parents or caregivers have to understand and accept experimental procedures and sign informed consent form.
• Use of effective contraceptive methods in female participants
• Regular menstrual cycle (26-32 days duration) in female subjects
• Moderate mental disability (IQ>40)
• Body mass index (BMI) comprised between 18.5 and 29.9 kg/m2, and body weight between 50 and 100 kg.
• Non-smokers
• Electroencephalogram record and general blood and urine analysis performed at screening visit should be within normal values. Minor or occasional variations in normal values are allowed if, in the opinion of Principal Investigator, taking into account the state of the science, they are not clinically significant, they do not pose risk for the subjects and they do not interfere in the evaluation of the investigational product. These variations and their non-relevance should be justified by writing.

Exclusion criteria

• Not fulfil inclusion criteria.
• Subjects with neurological disease other than FXS, relevant medical disease, co-morbid mental disorder or currently taking any treatment that could interfere with cognitive function or alter any key biomarkers and biochemical parameters analyzed.
• Having suffered from any major illness or undergoing major surgery in the last 12 months preceding the study.
• Regular ingestion of psychotropic drugs in the three months preceding the study. Exceptions were made for single doses of symptomatic medication administered up to the week preceding the trial.
• Current ingestion of vitamin supplements or catechins or non steroidal antiinflammatory drug (NSAID) in the two weeks preceding the study.
• History or clinical proof of gastrointestinal, hepatic or renal problems or any other cause that may alter processes of absorption, distribution, metabolism, or excretion of the drug, or that might suggest gastrointestinal irritation to drug.
• Subjects following a cognitive training.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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44 participants in 2 patient groups, including a placebo group

Fragile X syndrome experimental group

Active Comparator group

Description:

1. Administration of 400 mg/day of epigallocatechin-3-gallate (EGCG). Life Extension, Mega Green Tea Extract Decaffeinated, a dietary supplement containing EGCG extract (45% EGCGC). Dosage form: capsules of 200mg Route of administration: orally Dosage: 2 capsules per day (400 mg EGCG/day) Frequency: one capsule in the morning (fasting state) and a second capsule in the afternoon (before dinner). Treatment period: 3 months (from month 1 to month 4) 2. Cognitive training: non-pharmacological cognitive training 3 sessions per week (1 hour per session) by using the Feskits program.

Treatment:

Dietary Supplement: EGCG

Other: Cognitive training

Fragile X syndrome control group

Placebo Comparator group

Description:

1. Placebo administration. Placebo consists in capsules containing rice flour. Dosage form: capsules Route of administration: orally Dosage: 2 capsules per day Frequency: one capsule in the morning (fasting state) and a second capsule in the afternoon (before dinner). 2. Cognitive training: non-pharmacological cognitive training 3 sessions per week (1 hour per session) by using the Feskits program.

Treatment:

Other: Cognitive training

Dietary Supplement: Placebo