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

NCT01699711 | Completed Phase 2

• 1 other identifier: TESDAD
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

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.

Conditions

Down Syndrome (DS)

Keywords

APP function (amyloid precursor protein, cognitive stimulation, alzheimer disease. program

Outcome Measures

Primary Outcomes (2)

• 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.

  From predose baseline to 19 months (end of treatment)

• Change in Amyloidosis Biomarkers

  APP derived amyloid peptides in plasma (INNO-BIA)

  From predose baseline to 19 months (end of treatment)

Secondary Outcomes (8)

• Treatment compliance

  Predose baseline 3, 7, 13 months

• 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).

Study Arms (2)

Dietary Supplement: Epigallocatechin-3-gallate (EGCG)

ACTIVE COMPARATOR

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.

Dietary Supplement: Epigallocatechin-3-gallate (EGCG)

Placebo

PLACEBO COMPARATOR

No active treatment is given.

Dietary Supplement: Epigallocatechin-3-gallate (EGCG)

Interventions

Epigallocatechin-3-gallate (EGCG) 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.

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

Eligibility Criteria

• Age: 14 Years - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Have been diagnosed of DS neurological disease, aged between 14-29 years.
• Have given the consent to participate (official custody).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Parc de Salut Mar: lead

Study Sites (1)

IMIM (Institut Hospital del Mar d'Investigacions Mèdiques)

Barcelona, Barcelona, 08003, Spain

Location

Related Publications (1)

• 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.

  PMID: 27302362 DERIVED

MeSH Terms

Conditions

Down Syndrome; Alzheimer Disease

Interventions

epigallocatechin gallate

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: September 26, 2012
• First Posted: October 4, 2012
• Study Start: February 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: March 1, 2015
• Last Updated: February 11, 2016

Record last verified: 2016-02

Locations

ES (1)