Text Size

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

This study has been completed.
Sponsor:
Information provided by:
Parc de Salut Mar
ClinicalTrials.gov Identifier:
NCT01394796
First received: July 4, 2011
Last updated: March 12, 2013
Last verified: March 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Down Syndrome
 Dietary Supplement: Epigallocatechin-3-gallate (EGCG)
Drug: Placebo
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Egcg, a dyrk1a Inhibitor as Therapeutic Tool for Reversing Cognitive Deficits in Down Syndrome Individuals.

Resource links provided by NLM:

MedlinePlus related topics: Down Syndrome
U.S. FDA Resources

Further study details as provided by Parc de Salut Mar:

Primary Outcome Measures:
  • Memory [ Time Frame: Predose baseline and 3 months (end of treatment). ] [ Designated as safety issue: No ]
    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 [ Time Frame: Predose baseline and 3 months (end of treatment). ] [ Designated as safety issue: No ]
    Plasma homocysteine (Abbot AxyM),NAD (P)H: quinone oxireductase (NQOI) activity and dyrk1a gene expression in lymphocytes).


Secondary Outcome Measures:
  • Psychomotor speed [ Time Frame: Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. ] [ Designated as safety issue: No ]
    Motor Screening test (MOT)

  • Attention [ Time Frame: Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. ] [ Designated as safety issue: No ]

    Attention will be assessed using the following tests:

    Digit Span: forward recall (from the WMS-III). Spatial Span (SSP): forward recall.


  • Executive functions [ Time Frame: Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. ] [ Designated as safety issue: No ]

    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 [ Time Frame: Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. ] [ Designated as safety issue: No ]

    Visuomotor coordination will be assessed following the these tests:

    Purdue Pegboard Test Visuomotor precision


  • Functional outcome in daily living and adaptative behaviour [ Time Frame: Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. ] [ Designated as safety issue: No ]
    Functional outcome in daily living and adaptative behaviour Inventory for Client and Agency Planning (ICAP).

  • Quality of life [ Time Frame: Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. ] [ Designated as safety issue: No ]
    Kidscreen-27

  • Qualitative data on treatment effects [ Time Frame: Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. ] [ Designated as safety issue: No ]
    With a brief semi-structured self-made interview


Enrollment: 31
Study Start Date: May 2010
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Placebo Comparator: Placebo
No active substance is given.
 Drug: Placebo
No active treatment is given.

  Eligibility

Ages Eligible for Study:   14 Years to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Rafael de la Torre Fornells, Parc de Salu Mar
ClinicalTrials.gov Identifier: NCT01394796     History of Changes
Other Study ID Numbers: EGCG/DYRC1A/DS/IMIM/1
Study First Received: July 4, 2011
Last Updated: March 12, 2013
Health Authority: Spain: only Board approval required.

Additional relevant MeSH terms:
Down Syndrome
Epigallocatechin gallate
Mental Retardation
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Antioxidants
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Antimutagenic Agents
Anticarcinogenic Agents
Antineoplastic Agents
Therapeutic Uses
Neuroprotective Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on June 18, 2013