- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01699711
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
February 10, 2016 updated by: Rafael de la Torre, Parc de Salut Mar
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
87
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Barcelona, Spain, 08003
- IMIM (Institut Hospital del Mar d'Investigacions Mèdiques)
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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 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
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
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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.
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Placebo Comparator: Placebo
No active treatment is given.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Cognitive Evaluation
Time Frame: From predose baseline to 19 months (end of treatment)
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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.
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From predose baseline to 19 months (end of treatment)
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Change in Amyloidosis Biomarkers
Time Frame: From predose baseline to 19 months (end of treatment)
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APP derived amyloid peptides in plasma (INNO-BIA)
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From predose baseline to 19 months (end of treatment)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment compliance
Time Frame: Predose baseline 3, 7, 13 months
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Predose baseline 3, 7, 13 months
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Change in Biomarkers of lipid oxidation
Time Frame: Predose baseline: 3, 7, 13 months
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LDL (Low density lipoproteins), HDL (High density lipoprotein, cholesterol, triglycerides oxidized-LDL (Pentra Autoanalyzer, and ELISA Mercodia for LDLox
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Predose baseline: 3, 7, 13 months
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Change in DYRK1A activity biomarkers
Time Frame: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).
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Plasma homocysteine (Abbot AxyM), transthyretrin (ELISA) FOXO1 (DNA-binding ELISA nuclear extract from lymphocytes)
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Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).
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COMT val158met genetic polymorphism (catechol methyl transferase) (Taqman)
Time Frame: Predose baseline
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Predose baseline
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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).
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Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).
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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).
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Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).
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Changes in Neurophysiology
Time Frame: Predose baseline: 7, 13 months
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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).
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Predose baseline: 7, 13 months
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Changes in Neuroimaging
Time Frame: Predose baseline: 7, 13 months
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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.
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Predose baseline: 7, 13 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2012
Primary Completion (Actual)
June 1, 2014
Study Completion (Actual)
March 1, 2015
Study Registration Dates
First Submitted
September 26, 2012
First Submitted That Met QC Criteria
October 1, 2012
First Posted (Estimate)
October 4, 2012
Study Record Updates
Last Update Posted (Estimate)
February 11, 2016
Last Update Submitted That Met QC Criteria
February 10, 2016
Last Verified
February 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Intellectual Disability
- Abnormalities, Multiple
- Chromosome Disorders
- Down Syndrome
- 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
- TESDAD
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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