Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, is postulated to modulate dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) and amyloid beta precursor protein (APP) gene overexpression in the brains of Down syndrome mouse models. The clinical study is aimed at demonstrating that normalization of Dyrk1A and APP functions is a therapeutic approach to improve cognitive performance and decelerate AD (Alzheimer's disease) like progression.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
87
EGCG administration in Down syndrome patients will result in an improvement of their cognitive performance. A daily oral dose containing 9 mg/kg (range 6.9-12.7) of EGCG is given during twelve months.
IMIM (Institut Hospital del Mar d'Investigacions Mèdiques)
Barcelona, Barcelona, Spain
Change in Cognitive Evaluation
a.Intelligence Quotient \[Kaufman (K-BIT)\], b.Attention \[Spatial Span direct series (SSP), Choice Reaction Time (CRT) CANTAB battery\]c. Psychomotor Speed \[ (MOT) CANTAB battery\] d.Episodic Memory \[visuospatial: Paired Associates Learning (PAL) and visual: Pattern Recognition Memory (PRM) CANTAB battery; visuospatial learning Cued Recall Test (CRT) \] e.Executive Functions \[working memory: SSP CANTAB battery; verbal semantic fluency; inhibition: Cats and Dogs; planning: Tower of London-Drexel (TOLDX) mental flexibility: Weigl Card Sorting Test \] f.Language:\[ Expressive language: Boston naming test (BNT) ; Receptive language: Token Test (TT) g.Functional, quality of life and neuropsychiatric evaluation \[Adaptative Behaviour Assessment System (ABAS-II): Dementia Questionnaire for People with Intellectual Disabilities (DMR): Neuropsychiatric Inventory (NPI); quality of life: Kidscreen; semi-structured interview to evaluate subjective effects concerning relevant changes.
Time frame: From predose baseline to 19 months (end of treatment)
Change in Amyloidosis Biomarkers
APP derived amyloid peptides in plasma (INNO-BIA)
Time frame: From predose baseline to 19 months (end of treatment)
Treatment compliance
Time frame: Predose baseline 3, 7, 13 months
Change in Biomarkers of lipid oxidation
LDL (Low density lipoproteins), HDL (High density lipoprotein, cholesterol, triglycerides oxidized-LDL (Pentra Autoanalyzer, and ELISA Mercodia for LDLox
Time frame: Predose baseline: 3, 7, 13 months
Change in DYRK1A activity biomarkers
Plasma homocysteine (Abbot AxyM), transthyretrin (ELISA) FOXO1 (DNA-binding ELISA nuclear extract from lymphocytes)
Time frame: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).
COMT val158met genetic polymorphism (catechol methyl transferase) (Taqman)
Time frame: Predose baseline
Change in AST (SGOT -serum glutamic oxaloacetic transaminase-) and ALT (SGPT- Serum Glutamic Pyruvate Transaminase-) (Pentra Autoanalyzer, and ELISA Mercodia for LDLox)
Time frame: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).
Change in Body Composition by electrical impedance (TANITA-MC-180)
Time frame: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).
Changes in Neurophysiology
Parameters to be evaluated: (i) Motor threshold at Rest (MTR) for the Abductor Pollicis Brevis ( APB) muscle determination (ii) Basal single pulse response at rest for the APB at 110 of the MTR required, and (iii) Percentage of increase and decrease of the amplitude of the APB after double pulse, short and long pulse interval after transcranial magnetic stimulation (TMS).
Time frame: Predose baseline: 7, 13 months
Changes in Neuroimaging
Regional brain morphology and volume (FLAIR) sequence to assess possible white matter tissue macroscopic lesions), brain function in disease-specific neural systems: Intrinsic functional organization (i.e., functional connectivity) in the resting-state within the neural systems.
Time frame: Predose baseline: 7, 13 months
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