Egcg, a dyrk1a Inhibitor as Therapeutic Tool for Reversing Cognitive Deficits in Down Syndrome Individuals.

Study Overview
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Brief Summary
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There is a mounting evidence of the modulation properties of the major catechin in green tea, epigallocatechin-3-gallate (EGCG), on dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene overexpression in the brains of DS mouse models.The aims are to investigate the clinical benefits and safety of EGCG administration in young adults with DS, to establish short-term EGCG effects (three months) on neurocognitive performance, and to determine the persistency or reversibility of EGCG related effects after three months of discontinued use.

Official Title
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Egcg, a dyrk1a Inhibitor as Therapeutic Tool for Reversing Cognitive Deficits in Down Syndrome Individuals.

Conditions
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Down Syndrome

Intervention / Treatment
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* Dietary Supplement: Epigallocatechin-3-gallate (EGCG)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have been diagnosed of DS neurological disease, aged between 14-29 years, have given the consent to participate (official custody). Exclusion Criteria: Subjects with neurological disease other than DS, 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 three months before the study; Regular ingestion of medication in the month 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 AINE in the two weeks preceding the study. History 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 vegetarian diet. Practice of physical exercise for more than 2 hours per day or energy consume/consumption of more than 3000 kcal per week.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 29 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Epigallocatechin-3-gallate (EGCG)<br>EGCG normally works as a dietary supplement. EGCG administration in Down syndrome patients will result in an improvement of their cognitive performance.A a daily oral dose containing 9 mg/kg (range 6.9-12.7) of EGCG is given during three months. | Dietary Supplement: Epigallocatechin-3-gallate (EGCG)<br>* EGCG normally works as a dietary supplement. EGCG administration in Down syndrome patients will result in an improvement of their cognitive performance.A a daily oral dose containing 9 mg/kg (range 6.9-12.7) of EGCG is given during three months.<br>|
| Placebo Comparator: Placebo<br>No active substance is given. | Drug: Placebo<br>* No active treatment is given.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Memory | Memory and learning will be assessed using different neuropsicological tests: Pattern Recognition Memory (PRM), Fuld Object Memory Evaluation (FULD), Paired Associates Learning (PAL). | Predose baseline and 3 months (end of treatment). | 
| DYRK1A activity biomarkers | Plasma homocysteine (Abbot AxyM),NAD (P)H: quinone oxireductase (NQOI) activity and dyrk1a gene expression in lymphocytes). | Predose baseline and 3 months (end of treatment). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychomotor speed | Motor Screening test (MOT) | Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. | 
| Attention | Attention will be assessed using the following tests: Digit Span: forward recall (from the WMS-III). Spatial Span (SSP): forward recall. | Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. | 
| Executive functions | Executive functions will be assessed using the following tests: Digits Span: backward recall (from the WMS-III). Spatial Span (SSP): backward recall. Word fluency. Intra/Extra dimensional Set Shift (IED) | Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. | 
| Visuomotor coordination | Visuomotor coordination will be assessed following the these tests: Purdue Pegboard Test Visuomotor precision | Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. | 
| Functional outcome in daily living and adaptative behaviour | Functional outcome in daily living and adaptative behaviour Inventory for Client and Agency Planning (ICAP). | Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. | 
| Quality of life | Kidscreen-27 | Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. | 
| Qualitative data on treatment effects | With a brief semi-structured self-made interview | Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. |