Egcg, a dyrk1a Inhibitor as Therapeutic Tool for Reversing Cognitive Deficits in Down Syndrome Individuals.

Phase 2

Completed

• Conditions: Down Syndrome
• Interventions: Drug: Placebo; Dietary Supplement: Epigallocatechin-3-gallate (EGCG)

• Registration Number: NCT01394796
• Lead Sponsor: Parc de Salut Mar

Brief Summary

There is a mounting evidence of the modulation properties of the major catechin in green tea, epigallocatechin-3-gallate (EGCG), on dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene overexpression in the brains of DS mouse models.The aims are to investigate the clinical benefits and safety of EGCG administration in young adults with DS, to establish short-term EGCG effects (three months) on neurocognitive performance, and to determine the persistency or reversibility of EGCG related effects after three months of discontinued use.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-05
• Primary Completion: 2011-02
• Study Completion: 2011-02
• Study First Submitted: 2011-07-04
• Study First Submitted QC: 2011-07-13
• Study First Posted: 2011-07-14
• Status Verified: 2013-03
• Last Update Submitted: 2013-03-12
• Last Update Posted: 2013-03-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

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 were made 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	No active substance is given.
Epigallocatechin-3-gallate (EGCG)	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 a daily oral dose containing 9 mg/kg (range 6.9-12.7) of EGCG is given during three months.

Primary Outcome Measures

Name	Time	Method
Memory	Predose baseline and 3 months (end of treatment).	Memory and learning will be assessed using different neuropsicological tests: Pattern Recognition Memory (PRM), Fuld Object Memory Evaluation (FULD), Paired Associates Learning (PAL).
DYRK1A activity biomarkers	Predose baseline and 3 months (end of treatment).	Plasma homocysteine (Abbot AxyM),NAD (P)H: quinone oxireductase (NQOI) activity and dyrk1a gene expression in lymphocytes).

Secondary Outcome Measures

Name	Time	Method
Psychomotor speed	Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months.	Motor Screening test (MOT)
Attention	Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months.	Attention will be assessed using the following tests: Digit Span: forward recall (from the WMS-III). Spatial Span (SSP): forward recall.
Executive functions	Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months.	Executive functions will be assessed using the following tests: Digits Span: backward recall (from the WMS-III). Spatial Span (SSP): backward recall. Word fluency. Intra/Extra dimensional Set Shift (IED)
Visuomotor coordination	Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months.	Visuomotor coordination will be assessed following the these tests: Purdue Pegboard Test Visuomotor precision
Functional outcome in daily living and adaptative behaviour	Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months.	Functional outcome in daily living and adaptative behaviour Inventory for Client and Agency Planning (ICAP).
Quality of life	Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months.	Kidscreen-27
Qualitative data on treatment effects	Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months.	With a brief semi-structured self-made interview