Pediatric Exploratory Research Study of EGCG Use and Safety (PERSEUS)

Parc de Salut Mar76 enrolled

Overview

To evaluate safety and tolerability of epigallocatechin gallate (EGCG) in children from 6 to 12 years old with Intellectual Developmental Disorders (IDD) (Down syndrome or Fragile X syndrome).

This project first objective is to evaluate the safety and tolerability of the EGCG molecule (extracted form green tea) on children from 6 to 12 years old with Intellectual Development Disorder (Down syndrome and Fragile X syndrome). The secondary objective is to evaluate the benefits of the EGCG on attention, memory, executive functions, language and adaptive behaviour of these children. Dyrk1A and homocysteine in plasma will also be quantified, using them as biomarkers of efficacy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Down Syndrome Fragile X Syndrome

Interventions

EGCG FontUpDIETARY_SUPPLEMENT

Intake of 10mg/kg/day of EGCG, in the form of a dietary supplement (FontUp), two times a day.

Placebo FontUpOTHER

Intake of placebo, in the form of a dietary supplement (FontUp) (without EGCG), two times a day.

Eligibility

Sex: ALLMin age: 6 YearsMax age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Males and females aged 6 to 12 years on day 1 of treatment. * Clinical diagnosis of DS (full trisomy 21 or translocated) confirmed by chromosomal analysis (karyotyping) (Cohort I) or molecular diagnosis for FXS (mutations or premutations on the fragile mental retardation 1 gene-Fmr1 of the X chromosome) (Cohort II). A karyotype will be performed if not available in DS population. FXS molecular diagnosis will be performed if not available in FXS population. * A body-weight under 50 kg. * Parent or legal guardian/representative and caregiver willing to give written informed consent. * Mental age ≥ 3 years (Brunet-Lézine scale C version, picture naming and receptive vocabulary of the WPPSI-IV) * Study participants must have sufficient vision and hearing to participate in study evaluations. Mild hearing loss will be allowed. * Availability of parent/caregiver to accompany the subject to clinical visits, provide information about the subject's behavior and symptoms and ensure compliance with the medication schedule. * Subjects must be able to understand basic instructions. Naming and comprehension tasks of the WPPSI-IV will be used as an evaluation Exclusion Criteria: * Study participants with a current Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis of any primary psychiatric diagnosis (including autism spectrum disorder). For secondary diagnoses, such as attention deficit hyperactivity disorder, depression and conduct disorder, individuals under a fixed regime of medication (a regime that does not change in the 6 weeks prior to enrollment) are allowed as long as they are considered stable and their medication does not interfere with the progression of the study. * Personal history of infantile spasms, of epilepsy, of severe head trauma or Central Nervous System (CNS) infections (e.g. meningitis), with the exception of a single isolated febrile seizure. * Subjects with past history of seizures from primary causes (such as West syndrome and Lennox-Gastaut syndrome) or secondary causes. * Clinical history of moderate or severe Obstructive Sleep Apnea (OSA) as defined by Apnea-Hypopnea Index (AHI) (\>15 events per hour not well controlled by positive airway pressure therapy with stable settings) for at least 3 months prior to screening visit. * Subjects with thyroid disease that is not controlled (elevated basal Thyroid-stimulating hormone (TSH) \> 10 microU/mL) by thyroid hormone respective therapy. * Evidence of active, clinically significant, and unstable gastrointestinal, renal, hepatic, endocrine or cardiovascular system disease. * Cardiovascular, Systolic Blood Pressure (SBP) and/or Diastolic Blood Pressure (DBP) outside the 95th percentile for age; resting heart rate above 100 bpm. * Cardiovascular, ECG: clinically relevant ECG abnormalities at screening. Auscultation is mandatory part of cardiovascular examination. * Clinically significant abnormalities in laboratory test results at screening unless acceptable by the investigator. * Life-threatening illness or major surgery in the 3 months prior to the study. * Concomitant disease or condition or any clinically significant finding at screening that could interfere with the conduct of the study, or that would, in the opinion of the investigator, could lead to an unacceptable risk to the subject in this study. * Patients with risk factors of liver dysfunction such as previous history of liver disease, previous clinically significant hepatic abnormalities in laboratory testing, previous allergy or intolerance with liver disorders or any clinically significant abnormalities in hepatic laboratory testing at screening * Participation in other clinical trials in the last 3 months prior to the study. * Concomitant use of unapproved medication. * Current intake of vitamin supplements, catechins or products containing EGCG (i.e. TEAVIGO, Mega Green Tea capsules Life Extension or Font-UP Grand Fontaine Laboratories) for at least 3 months previous to the screening.

Locations (1)

IMIM (Institut Hospital del Mar d'Investigacions Mèdiques)

Barcelona, Spain

Outcomes

Primary Outcomes

Safety Outcome Measure : Adverse Events

Medical evaluations of incidence, nature, severity and causality of Adverse Events and Serious Adverse Events (SAE).

Time frame: From day -5 to day 252 (through study completion)

Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with blood analysis: Changes in liver function

The finding of an elevated alanine transaminase (ALT) or aspartate transaminase (AST) (\>3xULN), elevated total bilirubin (\>2xULN)

Time frame: Days -5, 5, 42, 84, 126, and 168.

Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with blood analysis: Changes in thyroid function

Elevated TSH (\>10 microU/mL) or any decrease of free T4 below the lower limit of normal values (\<0.8 ng/dL)

Time frame: Days -5, 42, 84, 126, and 168.

Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with blood analysis: Changes in renal function

Serum creatinine will be measured at various time points and an increase exceeding x1.5 ULN (upper limit of normal values) that is confirmed by a repeat testing within 3 days.

Time frame: Days -15, 84, and 168

Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with Electroencephalography (EEG): Clinical significant changes in cerebral activity

Electroencephalogram recording to detect epileptiform abnormalities and/or seizure activity and/or pro-convulsive effects in pediatric participants, enabling a deeper understanding of the pharmacological effects of the intervention.

Time frame: Days -15, 84, and 168

Safety Outcome Measure: Measure: Number of participants with treatment-related adverse events with supporting evidence with Electrocardiogram: Clinical significant changes in QTcF

Data from ClinicalTrials.gov

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Secondary Outcomes

Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Expressive language

Assessed by Picture Naming (PN) (WPPSI-IV). It is a verbal Comprehension subtest. It has 24 items. The child should name the drawings shown in the stimulus book. PN measures expressive language, ability and language development. Range score 0-24. Higher score is better outcome.

Time frame: Days -15, 168 and 252

Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Receptive language

Assessed by Receptive Vocabulary (RV)(WPPSI-IV). It is a verbal comprehension subtest. It has 31 items. The child selects the picture that best represents the word the examiner reads aloud. RV measures receptive language ability and language development. Range score 0-40. Higher score is better outcome.