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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 87
- 试验地点
- 2
- 主要终点
- Change in Cognitive Evaluation
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 14 Years 至 29 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have been diagnosed of DS neurological disease, aged between 14-29 years.
- •Have given the consent to participate (official custody).
排除标准
- •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.
结局指标
主要结局
Change in Cognitive Evaluation
时间窗: From predose baseline to 19 months (end of treatment)
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.
Change in Amyloidosis Biomarkers
时间窗: From predose baseline to 19 months (end of treatment)
APP derived amyloid peptides in plasma (INNO-BIA)
次要结局
- Change in Biomarkers of lipid oxidation(Predose baseline: 3, 7, 13 months)
- Change in DYRK1A activity biomarkers(Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).)
- COMT val158met genetic polymorphism (catechol methyl transferase) (Taqman)(Predose baseline)
- Change in AST (SGOT -serum glutamic oxaloacetic transaminase-) and ALT (SGPT- Serum Glutamic Pyruvate Transaminase-) (Pentra Autoanalyzer, and ELISA Mercodia for LDLox)(Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).)
- Treatment compliance(Predose baseline 3, 7, 13 months)
- Change in Body Composition by electrical impedance (TANITA-MC-180)(Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).)
- Changes in Neurophysiology(Predose baseline: 7, 13 months)
- Changes in Neuroimaging(Predose baseline: 7, 13 months)
研究者
Rafael de la Torre
PhD
Parc de Salut Mar