Clinical trial NCT01699711: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Down Syndrome (DS)
Keywords: APP function (amyloid precursor protein, cognitive stimulation, alzheimer disease. program
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
First posted: 2012-10-04
Enrollment: 87
Sex: ALL
Minimum age (years): 14
Maximum age (years): 29
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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 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.

Primary outcomes:
measure: Change in Cognitive Evaluation
timeFrame: From predose baseline to 19 months (end of treatment)
measure: Change in Amyloidosis Biomarkers
timeFrame: From predose baseline to 19 months (end of treatment)
Secondary outcomes:
measure: Treatment compliance
timeFrame: Predose baseline 3, 7, 13 months
measure: Change in Biomarkers of lipid oxidation
timeFrame: Predose baseline: 3, 7, 13 months
measure: Change in DYRK1A activity biomarkers
timeFrame: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).
measure: COMT val158met genetic polymorphism (catechol methyl transferase) (Taqman)
timeFrame: 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)
timeFrame: 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)
timeFrame: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).
measure: Changes in Neurophysiology
timeFrame: Predose baseline: 7, 13 months
measure: Changes in Neuroimaging
timeFrame: Predose baseline: 7, 13 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: IMIM (Institut Hospital del Mar d'Investigacions Mèdiques)
Study officials:
References:
citation: de la Torre R, de Sola S, Hernandez G, Farre M, Pujol J, Rodriguez J, Espadaler JM, Langohr K, Cuenca-Royo A, Principe A, Xicota L, Janel N, Catuara-Solarz S, Sanchez-Benavides G, Blehaut H, Duenas-Espin I, Del Hoyo L, Benejam B, Blanco-Hinojo L, Videla S, Fito M, Delabar JM, Dierssen M; TESDAD study group. Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Jul;15(8):801-810. doi: 10.1016/S1474-4422(16)30034-5.