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

Down Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01394796
• Other study ID #: EGCG/DYRC1A/DS/IMIM/1
• Status: Completed
• Phase: Phase 2
• First received: July 4, 2011
• Last updated: March 12, 2013
• Start date: May 2010
• Est. completion date: February 2011

Study information

• Verified date: March 2013
• Source: Parc de Salut Mar
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 29 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Dysfunction
• Down Syndrome
• Syndrome

Intervention

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.

Drug:
• Placebo
No active treatment is given.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Parc de Salut Mar

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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	Psychomotor speed	Motor Screening test (MOT)	Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Quality of life	Kidscreen-27	Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months.
Secondary	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.