ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01699711
Recruitment Status : Completed
First Posted : October 4, 2012
Last Update Posted : February 11, 2016
Sponsor:
Information provided by (Responsible Party):
Rafael de la Torre, Parc de Salut Mar

September 26, 2012
October 4, 2012
February 11, 2016
February 2012
June 2014   (Final data collection date for primary outcome measure)
  • Change in Cognitive Evaluation [ Time Frame: 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 [ Time Frame: From predose baseline to 19 months (end of treatment) ]
    APP derived amyloid peptides in plasma (INNO-BIA)
Same as current
Complete list of historical versions of study NCT01699711 on ClinicalTrials.gov Archive Site
  • Treatment compliance [ Time Frame: Predose baseline 3, 7, 13 months ]
  • Change in Biomarkers of lipid oxidation [ Time Frame: Predose baseline: 3, 7, 13 months ]
    LDL (Low density lipoproteins), HDL (High density lipoprotein, cholesterol, triglycerides oxidized-LDL (Pentra Autoanalyzer, and ELISA Mercodia for LDLox
  • Change in DYRK1A activity biomarkers [ Time Frame: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months). ]
    Plasma homocysteine (Abbot AxyM), transthyretrin (ELISA) FOXO1 (DNA-binding ELISA nuclear extract from lymphocytes)
  • 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 [ Time Frame: Predose baseline: 7, 13 months ]
    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).
  • Changes in Neuroimaging [ Time Frame: Predose baseline: 7, 13 months ]
    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.
Same as current
Not Provided
Not Provided
 
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
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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Down Syndrome (DS)
Dietary Supplement: Epigallocatechin-3-gallate (EGCG)
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.
  • Active Comparator: Dietary Supplement: Epigallocatechin-3-gallate (EGCG)
    EGCG normally works as a dietary supplement. 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.
    Intervention: Dietary Supplement: Epigallocatechin-3-gallate (EGCG)
  • Placebo Comparator: Placebo
    No active treatment is given.
    Intervention: Dietary Supplement: Epigallocatechin-3-gallate (EGCG)
de la Torre R, de Sola S, Hernandez G, Farré M, Pujol J, Rodriguez J, Espadaler JM, Langohr K, Cuenca-Royo A, Principe A, Xicota L, Janel N, Catuara-Solarz S, Sanchez-Benavides G, Bléhaut H, Dueñas-Espín I, Del Hoyo L, Benejam B, Blanco-Hinojo L, Videla S, Fitó 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
87
100
March 2015
June 2014   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
14 Years to 29 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
 
NCT01699711
TESDAD
No
Not Provided
Not Provided
Rafael de la Torre, Parc de Salut Mar
Parc de Salut Mar
Not Provided
Not Provided
Parc de Salut Mar
February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP