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Report for Clinical Trial NCT01699711

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Normalization of dyrk1A and APP Function as an Approach to Improve Cognitive Performance and Decelerate AD Progression in DS Subjects: Epigallocatechin Gallate as Therapeutic Tool

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.

NCT01699711 Down Syndrome (DS)
MeSH:Down Syndrome

1 Interventions

Name: Epigallocatechin-3-gallate (EGCG)

Description: 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.
Type: Dietary Supplement
Group Labels: 2

Dietary Supplement: Epigallocatechin-3-gallate (EGCG) Placebo


Primary Outcomes

Description: 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.

Measure: Change in Cognitive Evaluation

Time: From predose baseline to 19 months (end of treatment)

Description: APP derived amyloid peptides in plasma (INNO-BIA)

Measure: Change in Amyloidosis Biomarkers

Time: From predose baseline to 19 months (end of treatment)

Secondary Outcomes

Measure: Treatment compliance

Time: Predose baseline 3, 7, 13 months

Description: LDL (Low density lipoproteins), HDL (High density lipoprotein, cholesterol, triglycerides oxidized-LDL (Pentra Autoanalyzer, and ELISA Mercodia for LDLox

Measure: Change in Biomarkers of lipid oxidation

Time: Predose baseline: 3, 7, 13 months

Description: Plasma homocysteine (Abbot AxyM), transthyretrin (ELISA) FOXO1 (DNA-binding ELISA nuclear extract from lymphocytes)

Measure: Change in DYRK1A activity biomarkers

Time: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).

Measure: COMT val158met genetic polymorphism (catechol methyl transferase) (Taqman)

Time: Predose baseline

Measure: Change in AST (SGOT -serum glutamic oxaloacetic transaminase-) and ALT (SGPT- Serum Glutamic Pyruvate Transaminase-) (Pentra Autoanalyzer, and ELISA Mercodia for LDLox)

Time: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).

Measure: Change in Body Composition by electrical impedance (TANITA-MC-180)

Time: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).

Description: 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).

Measure: Changes in Neurophysiology

Time: Predose baseline: 7, 13 months

Description: 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.

Measure: Changes in Neuroimaging

Time: Predose baseline: 7, 13 months

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 V158M

COMT val158met genetic polymorphism (catechol methyl transferase) (Taqman). --- val158met ---



HPO Nodes