Clinical trial NCT03624556: Pediatric Exploratory Research Study of EGCG Use and Safety (PERSEUS)
Official title: Pediatric Exploratory Research Study of EGCG Use and Safety (PERSEUS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Down Syndrome
Fragile X Syndrome
Keywords: Down Syndrome (DS)
Fragile X Syndrome (FXS)
Intellectual Development Disorder (IDD)
FontUp
EGCG
Epigallocatechin gallate
Dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A)
Homocysteine
Dietary supplement
Green tea
IMIM
PERSEUS
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
Collaborators: name: Hospital Infantil Universitario Niño Jesús, Madrid, Spain
name: Instituto Hispalense de Pediatría, Sevilla, Spain
name: Hospital Universitario Marqués de Valdecilla
name: Institut Jerome Lejeune
First posted: 2018-08-10
Enrollment: 76
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cohort I (Down Syndrome children): Phase II Randomized, double-blind, placebo-controlled, parallel groups to evaluate safety and tolerability of EGCG in children. The experimental group will take 10mg/kg/day of FontUp (EGCG on a dietary supplement with chocolate like shake flavor, two times a day) while the placebo group will take the same product but without the EGCG in it, taken with the same posology.

Cohort II (Fragile X syndrome children): exploratory open label study (pilot study) to assess safety and tolerability of EGCG. These patients will receive 10mg/kg/day of FontUp.

This cohort will only be recruited in Spanish sites.
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety Outcome Measure : Adverse Events
timeFrame: From day -5 to day 252 (through study completion)
measure: Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with blood analysis: Changes in liver function
timeFrame: Days -5, 5, 42, 84, 126, and 168.
measure: Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with blood analysis: Changes in thyroid function
timeFrame: Days -5, 42, 84, 126, and 168.
measure: Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with blood analysis: Changes in renal function
timeFrame: Days -15, 84, and 168
measure: Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with Electroencephalography (EEG): Clinical significant changes in cerebral activity
timeFrame: Days -15, 84, and 168
measure: Safety Outcome Measure: Measure: Number of participants with treatment-related adverse events with supporting evidence with Electrocardiogram: Clinical significant changes in QTcF
timeFrame: Days -56 and 168
measure: Safety Outcome Measure: Measure: Number of participants with treatment-related adverse events with supporting evidence with Echocardiogram: Clinical significant changes in size of the chambers of the heart.
timeFrame: Days -56 and 168
measure: Safety Outcome Measure: Measure: Number of participants with treatment-related adverse events with supporting evidence with Echocardiogram: Clinical significant changes in pumping function of the heart.
timeFrame: Days -56 and 168
Secondary outcomes:
measure: Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Expressive language
timeFrame: Days -15, 168 and 252
measure: Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Receptive language
timeFrame: Days -1,168 and 252
measure: Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Memory and Learning
timeFrame: Days -1,168 and 252
measure: Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Working Memory (WM)
timeFrame: Days -1,168 and 252
measure: Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Verbal Fluency (VF)
timeFrame: Days -1,168 and 252
measure: Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in inhibition behavior
timeFrame: Days -1,168 and 252
measure: Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in mental flexibility
timeFrame: Days -1,84,168 and 252
measure: Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Visual-spatial Process
timeFrame: Days -1,168 and 252
measure: Functional Outcome Measure : IDD-CHILD Vineland Adaptive Behavior Scales Scale Parent/Caregiver Interview Form, Second Edition (VABS-II)(Vineland™-II survey version)
timeFrame: Days -1,168 and 252
Other outcomes:
measure: Exploratory Outcome: Efficacy Biomarkers analysis in plasma
timeFrame: Baseline, months 3 and 6
measure: Exploratory Outcome: Blood folate concentration
timeFrame: Months -1, 3 and 6
measure: Exploratory Outcome Targeted metabolomics
timeFrame: Months -1, 3 and 6
measure: Exploratory Outcome: Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P)
timeFrame: Baseline, months 6 and 9
measure: Exploratory Outcome: Observed Memory Questionnaire Parent Form (OMQ-PF)
timeFrame: Baseline, months 6 and 9
measure: Exploratory Outcome: Paediatric Quality of Life Inventory (PedsQL)
timeFrame: Baseline, months 6 and 9
measure: Exploratory Outcome: Children's Sleep habits questionnaire (CSHQ)
timeFrame: Baseline, months 6 and 9
measure: Exploratory Outcome: Aberrant Behavior Checklist (ABC)
timeFrame: Baseline, months 6 and 9
measure: Exploratory Outcome: Mediterranean Diet Quality Index for children and adolescents (KidMed Questionnaire)
timeFrame: Baseline, months 6 and 9
measure: Exploratory Outcome: Changes in Cognitive composite Z-score
timeFrame: Baseline, months 6 and 9
Locations:
city: Barcelona
country: Spain
facility: IMIM (Institut Hospital del Mar d'Investigacions Mèdiques)
Study officials:
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