Normalization of dyrk1A and APP Function as an Approach to Improve Cognitive Performance and Decelerate AD Progression in DS Subjects: Epigallocatechin Gallate as Therapeutic Tool

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2012 by Parc de Salut Mar.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Parc de Salut Mar
ClinicalTrials.gov Identifier:
NCT01699711
First received: September 26, 2012
Last updated: October 1, 2012
Last verified: October 2012
  Purpose

Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, is postulated to modulate dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) and amyloid beta precursor protein (APP) gene overexpression in the brains of Down syndrome mouse models. The clinical study is aimed at demonstrating that normalization of Dyrk1A and APP functions is a therapeutic approach to improve cognitive performance and decelerate AD (Alzheimer's disease) like progression.


Condition Intervention Phase
Down Syndrome (DS)
Dietary Supplement: Epigallocatechin-3-gallate (EGCG)
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: Normalization of dyrk1A and APP Function as an Approach to Improve Cognitive Performance and Decelerate AD Progression in DS Subjects: Epigallocatechin Gallate as Therapeutic Tool

Resource links provided by NLM:


Further study details as provided by Parc de Salut Mar:

Primary Outcome Measures:
  • Change in Cognitive Evaluation [ Time Frame: From predose baseline to 19 months (end of treatment) ] [ Designated as safety issue: No ]
    a.Intelligence Quotient [Kaufman (K-BIT)], b.Attention [Spatial Span direct series (SSP), Choice Reaction Time (CRT) CANTAB battery]c. Psychomotor Speed [ (MOT) CANTAB battery] d.Episodic Memory [visuospatial: Paired Associates Learning (PAL) and visual: Pattern Recognition Memory (PRM) CANTAB battery; visuospatial learning Cued Recall Test (CRT) ] e.Executive Functions [working memory: SSP CANTAB battery; verbal semantic fluency; inhibition: Cats and Dogs; planning: Tower of London-Drexel (TOLDX) mental flexibility: Weigl Card Sorting Test ] f.Language:[ Expressive language: Boston naming test (BNT) ; Receptive language: Token Test (TT) g.Functional, quality of life and neuropsychiatric evaluation [Adaptative Behaviour Assessment System (ABAS-II): Dementia Questionnaire for People with Intellectual Disabilities (DMR): Neuropsychiatric Inventory (NPI); quality of life: Kidscreen; semi-structured interview to evaluate subjective effects concerning relevant changes.

  • Change in Amyloidosis Biomarkers [ Time Frame: From predose baseline to 19 months (end of treatment) ] [ Designated as safety issue: No ]
    APP derived amyloid peptides in plasma (INNO-BIA)


Secondary Outcome Measures:
  • Treatment compliance [ Time Frame: Predose baseline 3, 7, 13 months ] [ Designated as safety issue: No ]
  • Change in Biomarkers of lipid oxidation [ Time Frame: Predose baseline: 3, 7, 13 months ] [ Designated as safety issue: No ]
    LDL (Low density lipoproteins), HDL (High density lipoprotein, cholesterol, triglycerides oxidized-LDL (Pentra Autoanalyzer, and ELISA Mercodia for LDLox

  • Change in DYRK1A activity biomarkers [ Time Frame: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months). ] [ Designated as safety issue: No ]
    Plasma homocysteine (Abbot AxyM), transthyretrin (ELISA) FOXO1 (DNA-binding ELISA nuclear extract from lymphocytes)

  • COMT val158met genetic polymorphism (catechol methyl transferase) (Taqman) [ Time Frame: Predose baseline ] [ Designated as safety issue: No ]
  • Change in AST (SGOT -serum glutamic oxaloacetic transaminase-) and ALT (SGPT- Serum Glutamic Pyruvate Transaminase-) (Pentra Autoanalyzer, and ELISA Mercodia for LDLox) [ Time Frame: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months). ] [ Designated as safety issue: Yes ]
  • Change in Body Composition by electrical impedance (TANITA-MC-180) [ Time Frame: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months). ] [ Designated as safety issue: No ]
  • Changes in Neurophysiology [ Time Frame: Predose baseline: 7, 13 months ] [ Designated as safety issue: No ]
    Parameters to be evaluated: (i) Motor threshold at Rest (MTR) for the Abductor Pollicis Brevis ( APB) muscle determination (ii) Basal single pulse response at rest for the APB at 110 of the MTR required, and (iii) Percentage of increase and decrease of the amplitude of the APB after double pulse, short and long pulse interval after transcranial magnetic stimulation (TMS).

  • Changes in Neuroimaging [ Time Frame: Predose baseline: 7, 13 months ] [ Designated as safety issue: No ]
    Regional brain morphology and volume (FLAIR) sequence to assess possible white matter tissue macroscopic lesions), brain function in disease-specific neural systems: Intrinsic functional organization (i.e., functional connectivity) in the resting-state within the neural systems.


Estimated Enrollment: 100
Study Start Date: March 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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 daily oral dose containing 9 mg/kg (range 6.9-12.7) of EGCG is given during twelve months.
Dietary Supplement: Epigallocatechin-3-gallate (EGCG)
EGCG administration in Down syndrome patients will result in an improvement of their cognitive performance. A daily oral dose containing 9 mg/kg (range 6.9-12.7) of EGCG is given during twelve months.
Placebo Comparator: 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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01699711

Contacts
Contact: Rafael De la Torre Fornell, PhD 0034933160484 rtorre@imim.es

Locations
Spain
IMIM (Institut Hospital del Mar d'Investigacions Mèdiques) Recruiting
Barcelona, Spain, 08003
Contact: Rafael De la Torre Fornell, PhD    0034933160484    rtorre@imim.es   
Principal Investigator: Rafael de la Torre, PhD         
Sponsors and Collaborators
Parc de Salut Mar
  More Information

No publications provided

Responsible Party: Parc de Salut Mar
ClinicalTrials.gov Identifier: NCT01699711     History of Changes
Other Study ID Numbers: TESDAD
Study First Received: September 26, 2012
Last Updated: October 1, 2012
Health Authority: Spain: Ethics Committee

Keywords provided by Parc de Salut Mar:
APP function (amyloid precursor protein, cognitive stimulation, alzheimer disease. program

Additional relevant MeSH terms:
Down Syndrome
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Epigallocatechin gallate
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 October 02, 2014