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

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.

Study Overview

• Status: Completed
• Conditions: Down Syndrome
• Intervention / Treatment: Dietary supplement: Epigallocatechin-3-gallate (EGCG); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 27 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; No active substance is given.	Drug: Placebo; No active treatment is given.
Active Comparator: 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.	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 a daily oral dose containing 9 mg/kg (range 6.9-12.7) of EGCG is given during three months.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Parc de Salut Mar

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: July 4, 2011
• First Submitted That Met QC Criteria: July 13, 2011
• First Posted (Estimate): July 14, 2011

Study Record Updates

• Last Update Posted (Estimate): March 13, 2013
• Last Update Submitted That Met QC Criteria: March 12, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Cognitive Dysfunction; Down Syndrome; Cognition Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Neuroprotective Agents; Protective Agents; Antioxidants; Anticarcinogenic Agents; Antimutagenic Agents; Epigallocatechin gallate
• Other Study ID Numbers: EGCG/DYRC1A/DS/IMIM/1