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

• ClinicalTrials.gov Identifier: NCT01394796
• Recruitment Status: Completed
• First Posted: July 14, 2011
• Last Update Posted: March 13, 2013
• Sponsor: Parc de Salut Mar
• Information provided by: Parc de Salut Mar

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Down Syndrome	Dietary Supplement: Epigallocatechin-3-gallate (EGCG); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Egcg, a dyrk1a Inhibitor as Therapeutic Tool for Reversing Cognitive Deficits in Down Syndrome Individuals.
• Study Start Date: May 2010
• Actual Primary Completion Date: February 2011
• Actual Study Completion Date: February 2011

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. Memory [ Time Frame: 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).
2. DYRK1A activity biomarkers [ Time Frame: 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 :

1. Psychomotor speed [ Time Frame: Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. ]
   Motor Screening test (MOT)
2. Attention [ Time Frame: 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.

3. Executive functions [ Time Frame: 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)

4. Visuomotor coordination [ Time Frame: 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

5. Functional outcome in daily living and adaptative behaviour [ Time Frame: 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).
6. Quality of life [ Time Frame: Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. ]
   Kidscreen-27
7. Qualitative data on treatment effects [ Time Frame: Predose baseline: at 1 month, 3 months (end of treatment) plus 6 months. ]
   With a brief semi-structured self-made interview

Eligibility Criteria

• Ages Eligible for Study: 14 Years to 29 Years (Child, Adult)
• Sexes Eligible for Study: All
• 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

• Responsible Party: Rafael de la Torre Fornells, Parc de Salu Mar
• ClinicalTrials.gov Identifier: NCT01394796
• Other Study ID Numbers: EGCG/DYRC1A/DS/IMIM/1
• First Posted: July 14, 2011
• Last Update Posted: March 13, 2013
• Last Verified: March 2013

Additional relevant MeSH terms:

Down Syndrome; Epigallocatechin gallate; Syndrome; Cognition Disorders; Cognitive Dysfunction; Disease; Pathologic Processes; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Neurocognitive Disorders; Mental Disorders; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Antimutagenic Agents; Anticarcinogenic Agents; Antineoplastic Agents; Neuroprotective Agents