Down Syndrome (DS)Phase 2NCT01699711
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
A Phase 2 study testing Epigallocatechin-3-gallate (EGCG) in people with Down Syndrome (DS), run by Parc de Salut Mar at 1 site in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 14 to 29 years
- Conditions the study is for
- Down Syndrome (DS)
- What is being tested?
- Epigallocatechin-3-gallate (EGCG)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 87 participants
- Where
- 1 siteSpain
- Study dates
- Feb 2012to Mar 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Have been diagnosed of DS neurological disease, aged between 14-29 years.
- Have given the consent to participate (official custody).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Spain1 site
IMIM (Institut Hospital del Mar d'Investigacions Mèdiques)
Barcelona, Barcelona, 08003
About this study
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.
- Conditions
- Down Syndrome (DS)
- Being tested
- Epigallocatechin-3-gallate (EGCG)
- Keywords
- APP function (amyloid precursor protein, cognitive stimulation, alzheimer disease. program
- Medical subject headings
- Down Syndrome, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epigallocatechin-3-gallate (EGCG)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.
| Study group | Role | What they receive |
|---|---|---|
| Dietary Supplement: Epigallocatechin-3-gallate (EGCG) | Active comparator | 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. Receives: Dietary Supplement: Epigallocatechin-3-gallate (EGCG) |
| Placebo | Placebo comparator | No active treatment is given. Receives: Dietary Supplement: Epigallocatechin-3-gallate (EGCG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cognitive Evaluation
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.
Measured: From predose baseline to 19 months (end of treatment)
Change in Amyloidosis Biomarkers
APP derived amyloid peptides in plasma (INNO-BIA)
Measured: From predose baseline to 19 months (end of treatment)
Secondary outcomes (8)
Treatment compliance
Measured: Predose baseline 3, 7, 13 months
Change in Biomarkers of lipid oxidation
LDL (Low density lipoproteins), HDL (High density lipoprotein, cholesterol, triglycerides oxidized-LDL (Pentra Autoanalyzer, and ELISA Mercodia for LDLox
Measured: Predose baseline: 3, 7, 13 months
Change in DYRK1A activity biomarkers
Plasma homocysteine (Abbot AxyM), transthyretrin (ELISA) FOXO1 (DNA-binding ELISA nuclear extract from lymphocytes)
Measured: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).
COMT val158met genetic polymorphism (catechol methyl transferase) (Taqman)
Measured: Predose baseline
Change in AST (SGOT -serum glutamic oxaloacetic transaminase-) and ALT (SGPT- Serum Glutamic Pyruvate Transaminase-) (Pentra Autoanalyzer, and ELISA Mercodia for LDLox)
Measured: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).
Change in Body Composition by electrical impedance (TANITA-MC-180)
Measured: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).
Changes in Neurophysiology
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).
Measured: Predose baseline: 7, 13 months
Changes in Neuroimaging
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.
Measured: Predose baseline: 7, 13 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2012 (estimated)
- Study startFeb 2012
- Primary completionJun 2014
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Down Syndrome (DS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Parc de Salut Mar
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rafael de la Torre, Parc de Salut Mar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01699711
- Sponsor's protocol ID
- TESDAD
- Status last verified
- Feb 2016
- First submitted
- 26 Sep 2012
- Last updated
- 11 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
de la Torre R, de Sola S, Hernandez G, Farre M, Pujol J, Rodriguez J, Espadaler JM, Langohr K, Cuenca-Royo A, Principe A, Xicota L, Janel N, Catuara-Solarz S, Sanchez-Benavides G, Blehaut H, Duenas-Espin I, Del Hoyo L, Benejam B, Blanco-Hinojo L, Videla S, Fito M, Delabar JM, Dierssen M; TESDAD study group. Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Jul;15(8):801-810. doi: 10.1016/S1474-4422(16)30034-5.
PubMed 27302362
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01699711
- Acronym / sponsor ID
- TESDAD
- Conditions
- Down Syndrome (DS)
- Keywords
- APP function (amyloid precursor protein, cognitive stimulation, alzheimer disease. program
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Parc de Salut MarUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Jun 2014 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 4 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dietary Supplement: Epigallocatechin-3-gallate (EGCG) | 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. |
| Placebo | Placebo comparator | Dietary Supplement: Epigallocatechin-3-gallate (EGCG)No active treatment is given. |
Who may qualify
- Ages
- 14 to 29 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Have been diagnosed of DS neurological disease, aged between 14-29 years.
- Have given the consent to participate (official custody).
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Dietary supplement | Dietary Supplement: Epigallocatechin-3-gallate (EGCG), Placebo |
Primary outcome
Change in Cognitive Evaluation
Time frame: From predose baseline to 19 months (end of treatment)
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)
APP derived amyloid peptides in plasma (INNO-BIA)
8 secondary outcomes
Treatment compliance
Time frame: Predose baseline 3, 7, 13 months
Change in Biomarkers of lipid oxidation
Time frame: Predose baseline: 3, 7, 13 months
Change in DYRK1A activity biomarkers
Time frame: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).
COMT val158met genetic polymorphism (catechol methyl transferase) (Taqman)
Time frame: Predose baseline
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).
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).
Changes in Neurophysiology
Time frame: Predose baseline: 7, 13 months
Changes in Neuroimaging
Time frame: Predose baseline: 7, 13 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2016.
- Derived from this study: PubMed 27302362de la Torre R, de Sola S, Hernandez G, Farre M, Pujol J, Rodriguez J, Espadaler JM, Langohr K, Cuenca-Royo A, Principe A, Xicota L, Janel N, Catuara-Solarz S, Sanchez-Benavides G, Blehaut H, Duenas-Espin I, Del Hoyo L, Benejam B, Blanco-Hinojo L, Videla S, Fito M, Delabar JM, Dierssen M; TESDAD study group. Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Jul;15(8):801-810. doi: 10.1016/S1474-4422(16)30034-5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Epigallocatechin-3-gallate (EGCG) in people with Down Syndrome (DS), run by Parc de Salut Mar at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cognitive Evaluation (time frame: From predose baseline to 19 months (end of treatment)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01699711, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2016.