Down SyndromePERSEUSNCT03624556
Pediatric Exploratory Research Study of EGCG Use and Safety (PERSEUS)
A study testing EGCG FontUp in people with Down Syndrome and Fragile X Syndrome, run by Parc de Salut Mar at 1 site in Spain.
Trial summary
To evaluate safety and tolerability of epigallocatechin gallate (EGCG) in children from 6 to 12 years old with Intellectual Developmental Disorders (IDD) (Down syndrome or Fragile X syndrome). Read more about this study
- Who is it for?
- Ages 6 to 12 years
- Conditions the study is for
- Down Syndrome, Fragile X Syndrome
- What is being tested?
- EGCG FontUp
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 1 siteSpain
- Study dates
- 29 Jan 2018to 30 Nov 2020
- Phase
- Interventional
- 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 6 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Males and females aged 6 to 12 years on day 1 of treatment.
- Clinical diagnosis of DS (full trisomy 21 or translocated) confirmed by chromosomal analysis (karyotyping) (Cohort I) or molecular diagnosis for FXS (mutations or premutations on the fragile mental retardation 1 gene-Fmr1 of the X chromosome) (Cohort II). A karyotype will be performed if not available in DS population. FXS molecular diagnosis will be performed if not available in FXS population.
- A body-weight under 50 kg.
- Parent or legal guardian/representative and caregiver willing to give written informed consent.
- Mental age ≥ 3 years (Brunet-Lézine scale C version, picture naming and receptive vocabulary of the WPPSI-IV)
- Study participants must have sufficient vision and hearing to participate in study evaluations. Mild hearing loss will be allowed.
- Availability of parent/caregiver to accompany the subject to clinical visits, provide information about the subject's behavior and symptoms and ensure compliance with the medication schedule.
- Subjects must be able to understand basic instructions. Naming and comprehension tasks of the WPPSI-IV will be used as an evaluation
Who cannot join
- Study participants with a current Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis of any primary psychiatric diagnosis (including autism spectrum disorder). For secondary diagnoses, such as attention deficit hyperactivity disorder, depression and conduct disorder, individuals under a fixed regime of medication (a regime that does not change in the 6 weeks prior to enrollment) are allowed as long as they are considered stable and their medication does not interfere with the progression of the study.
- Personal history of infantile spasms, of epilepsy, of severe head trauma or Central Nervous System (CNS) infections (e.g. meningitis), with the exception of a single isolated febrile seizure.
- Subjects with past history of seizures from primary causes (such as West syndrome and Lennox-Gastaut syndrome) or secondary causes.
- Clinical history of moderate or severe Obstructive Sleep Apnea (OSA) as defined by Apnea-Hypopnea Index (AHI) (>15 events per hour not well controlled by positive airway pressure therapy with stable settings) for at least 3 months prior to screening visit.
- Subjects with thyroid disease that is not controlled (elevated basal Thyroid-stimulating hormone (TSH) > 10 microU/mL) by thyroid hormone respective therapy.
- Evidence of active, clinically significant, and unstable gastrointestinal, renal, hepatic, endocrine or cardiovascular system disease.
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- Cardiovascular, Systolic Blood Pressure (SBP) and/or Diastolic Blood Pressure (DBP) outside the 95th percentile for age; resting heart rate above 100 bpm.
- Cardiovascular, ECG: clinically relevant ECG abnormalities at screening. Auscultation is mandatory part of cardiovascular examination.
- Clinically significant abnormalities in laboratory test results at screening unless acceptable by the investigator.
- Life-threatening illness or major surgery in the 3 months prior to the study.
- Concomitant disease or condition or any clinically significant finding at screening that could interfere with the conduct of the study, or that would, in the opinion of the investigator, could lead to an unacceptable risk to the subject in this study.
- Patients with risk factors of liver dysfunction such as previous history of liver disease, previous clinically significant hepatic abnormalities in laboratory testing, previous allergy or intolerance with liver disorders or any clinically significant abnormalities in hepatic laboratory testing at screening
- Participation in other clinical trials in the last 3 months prior to the study.
- Concomitant use of unapproved medication.
- Current intake of vitamin supplements, catechins or products containing EGCG (i.e. TEAVIGO, Mega Green Tea capsules Life Extension or Font-UP Grand Fontaine Laboratories) for at least 3 months previous to the screening.
Trial locations and contacts
1 site in 1 country.
Spain1 site
IMIM (Institut Hospital del Mar d'Investigacions Mèdiques)
Barcelona, 08003
About this study
To evaluate safety and tolerability of epigallocatechin gallate (EGCG) in children from 6 to 12 years old with Intellectual Developmental Disorders (IDD) (Down syndrome or Fragile X syndrome).
Read the detailed description
This project first objective is to evaluate the safety and tolerability of the EGCG molecule (extracted form green tea) on children from 6 to 12 years old with Intellectual Development Disorder (Down syndrome and Fragile X syndrome).
The secondary objective is to evaluate the benefits of the EGCG on attention, memory, executive functions, language and adaptive behaviour of these children. Dyrk1A and homocysteine in plasma will also be quantified, using them as biomarkers of efficacy.
- Conditions
- Down Syndrome, Fragile X Syndrome
- Being tested
- EGCG FontUp, Placebo FontUp
- Keywords
- Down Syndrome (DS), Fragile X Syndrome (FXS), Intellectual Development Disorder (IDD), FontUp, EGCG, Epigallocatechin gallate, Dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A), Homocysteine, Dietary supplement, Green tea, IMIM, PERSEUS
- Medical subject headings
- Down Syndrome, Fragile X Syndrome, Intellectual Disability
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EGCG FontUpDietary supplement
Intake of 10mg/kg/day of EGCG, in the form of a dietary supplement (FontUp), two times a day.
Placebo FontUpOther
Intake of placebo, in the form of a dietary supplement (FontUp) (without EGCG), two times a day.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group DS and FXS | Experimental | Cohort 1: a 35 DS children group taking EGCG FontUp. Cohort 2: a 6 FXS children group taking EGCG FontUp. (Experimental open-label) Receives: Dietary Supplement: EGCG FontUp |
| Control group DS | Placebo comparator | Cohort 1: a 35 DS children group taking placebo FontUp. Receives: Other: Placebo FontUp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Outcome Measure : Adverse Events
Medical evaluations of incidence, nature, severity and causality of Adverse Events and Serious Adverse Events (SAE).
Measured: From day -5 to day 252 (through study completion)
Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with blood analysis: Changes in liver function
The finding of an elevated alanine transaminase (ALT) or aspartate transaminase (AST) (>3xULN), elevated total bilirubin (>2xULN)
Measured: Days -5, 5, 42, 84, 126, and 168.
Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with blood analysis: Changes in thyroid function
Elevated TSH (>10 microU/mL) or any decrease of free T4 below the lower limit of normal values (<0.8 ng/dL)
Measured: Days -5, 42, 84, 126, and 168.
Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with blood analysis: Changes in renal function
Serum creatinine will be measured at various time points and an increase exceeding x1.5 ULN (upper limit of normal values) that is confirmed by a repeat testing within 3 days.
Measured: Days -15, 84, and 168
Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with Electroencephalography (EEG): Clinical significant changes in cerebral activity
Electroencephalogram recording to detect epileptiform abnormalities and/or seizure activity and/or pro-convulsive effects in pediatric participants, enabling a deeper understanding of the pharmacological effects of the intervention.
Measured: Days -15, 84, and 168
Safety Outcome Measure: Measure: Number of participants with treatment-related adverse events with supporting evidence with Electrocardiogram: Clinical significant changes in QTcF
A QTcF (Fridericia's correction) value (mean of the three measurements) exceeding 500 ms when confirmed in repeat measurement within 15-30 minutes will be recorded as SAE.
A QTcF value exceeding a change from screening (mean of three time-matched measurements) of 60 ms when confirmed in repeat measurement within 15-30 minutes will be recorded as SAE.
Measured: Days -56 and 168
Safety Outcome Measure: Measure: Number of participants with treatment-related adverse events with supporting evidence with Echocardiogram: Clinical significant changes in size of the chambers of the heart.
Doppler echocardiogram is used to look at how blood flows through the heart chambers, heart valves, and blood vessels. The movement of the blood reflects sound waves to a transducer. The ultrasound computer then measures the direction and speed of the blood flowing through heart and blood vessels.
Measured: Days -56 and 168
Safety Outcome Measure: Measure: Number of participants with treatment-related adverse events with supporting evidence with Echocardiogram: Clinical significant changes in pumping function of the heart.
This measure is known as an ejection fraction or EF.
Measured: Days -56 and 168
Secondary outcomes (9)
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Expressive language
Assessed by Picture Naming (PN) (WPPSI-IV). It is a verbal Comprehension subtest. It has 24 items. The child should name the drawings shown in the stimulus book. PN measures expressive language, ability and language development. Range score 0-24. Higher score is better outcome.
Measured: Days -15, 168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Receptive language
Assessed by Receptive Vocabulary (RV)(WPPSI-IV). It is a verbal comprehension subtest. It has 31 items. The child selects the picture that best represents the word the examiner reads aloud. RV measures receptive language ability and language development. Range score 0-40. Higher score is better outcome.
Measured: Days -1,168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Memory and Learning
Assessed by Sentence Repetition (NEPSY-II): This subtest is designed to assess the ability to repeat sentences of increasing complexity and length. The child is read a series of sentences and asked to recall each sentence immediately after it is presented. Range score 0-34. Higher score is better outcome.
Measured: Days -1,168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Working Memory (WM)
Assessed by Picture memory (WPPSI-IV). This subtest measures visual WM. It has 35 items. The child views a stimulus page of pictures for a specified time and then selects these pictures from options on a response page, for which a set of stimuli is viewed and then recognized from among a set of responses. Range score 0-35. Higher score is better outcome.
Measured: Days -1,168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Verbal Fluency (VF)
Subjects are asked to generate as many words as possible in 1 minute belonging to the category of "animals". No range score. A higher score is better outcome.
Measured: Days -1,168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in inhibition behavior
Assessed by Cats \& Dogs Test. 16 pictures presented on a single strip of card (two trials with two conditions, control and experimental-inhibition). Measures of task accuracy in the experimental inhibition trial (total number of correct responses, range score 0-16) and total time performance (in seconds) were included in the analyses.
Measured: Days -1,168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in mental flexibility
Assessed by Dimensional Change Card Sort (DCCS). Sort a series of bivalent test cards, according to one dimension(colour) or another(shape). Range score 0-24, higher score is better outcome.
Measured: Days -1,84,168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Visual-spatial Process
Assessed by Blocks Design(WPPSI-IV). It is a visual spatial subtest which has 17 items. It measures ability to analyze and synthesize abstract visual stimuli. Range score 0-34, higher score is better outcome.
Measured: Days -1,168 and 252
Functional Outcome Measure : IDD-CHILD Vineland Adaptive Behavior Scales Scale Parent/Caregiver Interview Form, Second Edition (VABS-II)(Vineland™-II survey version)
Changes in adaptive behavior
- A. Communication domain: Sum of A1+A2+A3. Range Score 0-198
- A1. Receptive subdomain: Range Score 0-40
- A2. Expressive subdomain: Range Score 0-108
- A3. Written subdomain: Range Score 0-50
- B. Daily living skills domain: Sum of B1+B2+B3. Range Score 0-109
- B1. Personal subdomain: Range Score 0-82
- B2. Domestic subdomain: Range Score 0-48
- B3. Community subdomain: Range Score 0-88
- C. Socialization domain: Sum of C1+C2+C3. Range Score 0-180
- C1. Interpersonal relationships subdomain: Range Score 0-64
- C2. Play and leisure time subdomain: Range Score 0-62
- C3. Coping skills subdomain: Range Score 0-60
- Total score: Sum of A+B+C. Range Score 0-576
For all measures: a higher score is a better outcome
Measured: Days -1,168 and 252
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2018
- Study start29 Jan 2018
- Primary completion29 Mar 2020
- Study completion30 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Down SyndromeStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Cohort I (Down Syndrome children): Phase II Randomized, double-blind, placebo-controlled, parallel groups to evaluate safety and tolerability of EGCG in children. The experimental group will take 10mg/kg/day of FontUp (EGCG on a dietary supplement with chocolate like shake flavor, two times a day) while the placebo group will take the same product but without the EGCG in it, taken with the same posology. Cohort II (Fragile X syndrome children): exploratory open label study (pilot study) to assess safety and tolerability of EGCG. These patients will receive 10mg/kg/day of FontUp. This cohort will only be recruited in Spanish sites.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Parc de Salut Mar
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Infantil Universitario Niño Jesús, Madrid, Spain, Instituto Hispalense de Pediatría, Sevilla, Spain, Hospital Universitario Marqués de Valdecilla, Institut Jerome Lejeune
- Responsible party
- Principal investigator, Rafael de la Torre, Parc de Salut Mar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03624556
- Sponsor's protocol ID
- PERSEUS/1
- Acronym
- PERSEUS
- Status last verified
- Jun 2021
- First submitted
- 6 Jun 2018
- Last updated
- 11 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Nagle DG, Ferreira D, Zhou YD. Epigallocatechin-3-gallate (EGCG): chemical and biomedical perspectives. Phytochemistry. 2006 Sep;67(17):1849-55. doi: 10.1016/j.phytochem.2006.06.020. Epub 2006 Jul 31.
PubMed 16876833Megarbane A, Ravel A, Mircher C, Sturtz F, Grattau Y, Rethore MO, Delabar JM, Mobley WC. The 50th anniversary of the discovery of trisomy 21: the past, present, and future of research and treatment of Down syndrome. Genet Med. 2009 Sep;11(9):611-6. doi: 10.1097/GIM.0b013e3181b2e34c.
PubMed 19636252Khoshnood B, Greenlees R, Loane M, Dolk H; EUROCAT Project Management Committee; EUROCAT Working Group. Paper 2: EUROCAT public health indicators for congenital anomalies in Europe. Birth Defects Res A Clin Mol Teratol. 2011 Mar;91 Suppl 1(Suppl 1):S16-22. doi: 10.1002/bdra.20776. Epub 2011 Mar 4.
PubMed 21381186Vicari S, Carlesimo GA. Short-term memory deficits are not uniform in Down and Williams syndromes. Neuropsychol Rev. 2006 Jun;16(2):87-94. doi: 10.1007/s11065-006-9008-4. Epub 2006 Aug 9.
PubMed 16967345Ronan A, Fagan K, Christie L, Conroy J, Nowak NJ, Turner G. Familial 4.3 Mb duplication of 21q22 sheds new light on the Down syndrome critical region. J Med Genet. 2007 Jul;44(7):448-51. doi: 10.1136/jmg.2006.047373. Epub 2007 Jan 19.
PubMed 17237124Dowjat WK, Adayev T, Kuchna I, Nowicki K, Palminiello S, Hwang YW, Wegiel J. Trisomy-driven overexpression of DYRK1A kinase in the brain of subjects with Down syndrome. Neurosci Lett. 2007 Feb 8;413(1):77-81. doi: 10.1016/j.neulet.2006.11.026. Epub 2006 Dec 4.
PubMed 17145134Altafaj X, Dierssen M, Baamonde C, Marti E, Visa J, Guimera J, Oset M, Gonzalez JR, Florez J, Fillat C, Estivill X. Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome. Hum Mol Genet. 2001 Sep 1;10(18):1915-23. doi: 10.1093/hmg/10.18.1915.
PubMed 11555628Belichenko PV, Kleschevnikov AM, Salehi A, Epstein CJ, Mobley WC. Synaptic and cognitive abnormalities in mouse models of Down syndrome: exploring genotype-phenotype relationships. J Comp Neurol. 2007 Oct 1;504(4):329-45. doi: 10.1002/cne.21433.
PubMed 17663443Dierssen M. Down syndrome: the brain in trisomic mode. Nat Rev Neurosci. 2012 Dec;13(12):844-58. doi: 10.1038/nrn3314.
PubMed 23165261Ji J, Lee H, Argiropoulos B, Dorrani N, Mann J, Martinez-Agosto JA, Gomez-Ospina N, Gallant N, Bernstein JA, Hudgins L, Slattery L, Isidor B, Le Caignec C, David A, Obersztyn E, Wisniowiecka-Kowalnik B, Fox M, Deignan JL, Vilain E, Hendricks E, Horton Harr M, Noon SE, Jackson JR, Wilkens A, Mirzaa G, Salamon N, Abramson J, Zackai EH, Krantz I, Innes AM, Nelson SF, Grody WW, Quintero-Rivera F. DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies. Eur J Hum Genet. 2015 Nov;23(11):1473-81. doi: 10.1038/ejhg.2015.71. Epub 2015 May 6.
PubMed 25944381Benavides-Piccione R, Dierssen M, Ballesteros-Yanez I, Martinez de Lagran M, Arbones ML, Fotaki V, DeFelipe J, Elston GN. Alterations in the phenotype of neocortical pyramidal cells in the Dyrk1A+/- mouse. Neurobiol Dis. 2005 Oct;20(1):115-22. doi: 10.1016/j.nbd.2005.02.004.
PubMed 16137572Pujol J, del Hoyo L, Blanco-Hinojo L, de Sola S, Macia D, Martinez-Vilavella G, Amor M, Deus J, Rodriguez J, Farre M, Dierssen M, de la Torre R. Anomalous brain functional connectivity contributing to poor adaptive behavior in Down syndrome. Cortex. 2015 Mar;64:148-56. doi: 10.1016/j.cortex.2014.10.012. Epub 2014 Oct 28.
PubMed 25461715de Sola S, de la Torre R, Sanchez-Benavides G, Benejam B, Cuenca-Royo A, Del Hoyo L, Rodriguez J, Catuara-Solarz S, Sanchez-Gutierrez J, Duenas-Espin I, Hernandez G, Pena-Casanova J, Langohr K, Videla S, Blehaut H, Farre M, Dierssen M; TESDAD Study Group. A new cognitive evaluation battery for Down syndrome and its relevance for clinical trials. Front Psychol. 2015 Jun 4;6:708. doi: 10.3389/fpsyg.2015.00708. eCollection 2015.
PubMed 26089807Ruiz-Mejias M, Martinez de Lagran M, Mattia M, Castano-Prat P, Perez-Mendez L, Ciria-Suarez L, Gener T, Sancristobal B, Garcia-Ojalvo J, Gruart A, Delgado-Garcia JM, Sanchez-Vives MV, Dierssen M. Overexpression of Dyrk1A, a Down Syndrome Candidate, Decreases Excitability and Impairs Gamma Oscillations in the Prefrontal Cortex. J Neurosci. 2016 Mar 30;36(13):3648-59. doi: 10.1523/JNEUROSCI.2517-15.2016.
PubMed 27030752Ruben K, Wurzlbauer A, Walte A, Sippl W, Bracher F, Becker W. Selectivity Profiling and Biological Activity of Novel beta-Carbolines as Potent and Selective DYRK1 Kinase Inhibitors. PLoS One. 2015 Jul 20;10(7):e0132453. doi: 10.1371/journal.pone.0132453. eCollection 2015.
PubMed 26192590
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pediatric Exploratory Research Study of EGCG Use and Safety (PERSEUS)
- ClinicalTrials.gov ID
- NCT03624556
- Acronym / sponsor ID
- PERSEUS / PERSEUS/1
- Conditions
- Down Syndrome, Fragile X Syndrome
- Keywords
- Down Syndrome (DS), Fragile X Syndrome (FXS), Intellectual Development Disorder (IDD), FontUp, EGCG, Epigallocatechin gallate, Dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A), Homocysteine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Parc de Salut MarUniversity, hospital or other
- Collaborators
- Hospital Infantil Universitario Niño Jesús, Madrid, Spain, Instituto Hispalense de Pediatría, Sevilla, Spain, Hospital Universitario Marqués de Valdecilla, Institut Jerome Lejeune
- Study start
- 29 Jan 2018 (actual)
- Primary completion
- 29 Mar 2020 (actual)
- Study completion
- 30 Nov 2020 (actual)
- First posted
- 10 Aug 2018 (actual)
- 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.
To evaluate safety and tolerability of epigallocatechin gallate (EGCG) in children from 6 to 12 years old with Intellectual Developmental Disorders (IDD) (Down syndrome or Fragile X syndrome).
Detailed description
This project first objective is to evaluate the safety and tolerability of the EGCG molecule (extracted form green tea) on children from 6 to 12 years old with Intellectual Development Disorder (Down syndrome and Fragile X syndrome).
The secondary objective is to evaluate the benefits of the EGCG on attention, memory, executive functions, language and adaptive behaviour of these children. Dyrk1A and homocysteine in plasma will also be quantified, using them as biomarkers of efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Cohort I (Down Syndrome children): Phase II Randomized, double-blind, placebo-controlled, parallel groups to evaluate safety and tolerability of EGCG in children. The experimental group will take 10mg/kg/day of FontUp (EGCG on a dietary supplement with chocolate like shake flavor, two times a day) while the placebo group will take the same product but without the EGCG in it, taken with the same posology. Cohort II (Fragile X syndrome children): exploratory open label study (pilot study) to assess safety and tolerability of EGCG. These patients will receive 10mg/kg/day of FontUp. This cohort will only be recruited in Spanish sites.
| Arm | Type | Receives |
|---|---|---|
| Experimental group DS and FXS | Experimental | Dietary Supplement: EGCG FontUpCohort 1: a 35 DS children group taking EGCG FontUp. Cohort 2: a 6 FXS children group taking EGCG FontUp. (Experimental open-label) |
| Control group DS | Placebo comparator | Other: Placebo FontUpCohort 1: a 35 DS children group taking placebo FontUp. |
Who may qualify
- Ages
- 6 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Males and females aged 6 to 12 years on day 1 of treatment.
- Clinical diagnosis of DS (full trisomy 21 or translocated) confirmed by chromosomal analysis (karyotyping) (Cohort I) or molecular diagnosis for FXS (mutations or premutations on the fragile mental retardation 1 gene-Fmr1 of the X chromosome) (Cohort II). A karyotype will be performed if not available in DS population. FXS molecular diagnosis will be performed if not available in FXS population.
- A body-weight under 50 kg.
- Parent or legal guardian/representative and caregiver willing to give written informed consent.
- Mental age ≥ 3 years (Brunet-Lézine scale C version, picture naming and receptive vocabulary of the WPPSI-IV)
Key exclusion criteria (15 listed)
- Study participants with a current Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis of any primary psychiatric diagnosis (including autism spectrum disorder). For secondary diagnoses, such as attention deficit hyperactivity disorder, depression and conduct disorder, individuals under a fixed regime of medication (a regime that does not change in the 6 weeks prior to enrollment) are allowed as long as they are considered stable and their medication does not interfere with the progression of the study.
- Personal history of infantile spasms, of epilepsy, of severe head trauma or Central Nervous System (CNS) infections (e.g. meningitis), with the exception of a single isolated febrile seizure.
- Subjects with past history of seizures from primary causes (such as West syndrome and Lennox-Gastaut syndrome) or secondary causes.
- Clinical history of moderate or severe Obstructive Sleep Apnea (OSA) as defined by Apnea-Hypopnea Index (AHI) (>15 events per hour not well controlled by positive airway pressure therapy with stable settings) for at least 3 months prior to screening visit.
- Subjects with thyroid disease that is not controlled (elevated basal Thyroid-stimulating hormone (TSH) > 10 microU/mL) by thyroid hormone respective therapy.
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 |
|---|---|---|
| EGCG FontUpIntake of 10mg/kg/day of EGCG, in the form of a dietary supplement (FontUp), two times a day. | Dietary supplement | Experimental group DS and FXS |
| Placebo FontUpIntake of placebo, in the form of a dietary supplement (FontUp) (without EGCG), two times a day. | Other | Control group DS |
Primary outcome
Safety Outcome Measure : Adverse Events
Time frame: From day -5 to day 252 (through study completion)
Medical evaluations of incidence, nature, severity and causality of Adverse Events and Serious Adverse Events (SAE).
Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with blood analysis: Changes in liver function
Time frame: Days -5, 5, 42, 84, 126, and 168.
The finding of an elevated alanine transaminase (ALT) or aspartate transaminase (AST) (>3xULN), elevated total bilirubin (>2xULN)
Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with blood analysis: Changes in thyroid function
Time frame: Days -5, 42, 84, 126, and 168.
Elevated TSH (>10 microU/mL) or any decrease of free T4 below the lower limit of normal values (<0.8 ng/dL)
Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with blood analysis: Changes in renal function
Time frame: Days -15, 84, and 168
Serum creatinine will be measured at various time points and an increase exceeding x1.5 ULN (upper limit of normal values) that is confirmed by a repeat testing within 3 days.
Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with Electroencephalography (EEG): Clinical significant changes in cerebral activity
Time frame: Days -15, 84, and 168
Electroencephalogram recording to detect epileptiform abnormalities and/or seizure activity and/or pro-convulsive effects in pediatric participants, enabling a deeper understanding of the pharmacological effects of the intervention.
Safety Outcome Measure: Measure: Number of participants with treatment-related adverse events with supporting evidence with Electrocardiogram: Clinical significant changes in QTcF
Time frame: Days -56 and 168
A QTcF (Fridericia's correction) value (mean of the three measurements) exceeding 500 ms when confirmed in repeat measurement within 15-30 minutes will be recorded as SAE. A QTcF value exceeding a change from screening (mean of three time-matched measurements) of 60 ms when confirmed in repeat measurement within 15-30 minutes will be recorded as SAE.
Safety Outcome Measure: Measure: Number of participants with treatment-related adverse events with supporting evidence with Echocardiogram: Clinical significant changes in size of the chambers of the heart.
Time frame: Days -56 and 168
Doppler echocardiogram is used to look at how blood flows through the heart chambers, heart valves, and blood vessels. The movement of the blood reflects sound waves to a transducer. The ultrasound computer then measures the direction and speed of the blood flowing through heart and blood vessels.
Safety Outcome Measure: Measure: Number of participants with treatment-related adverse events with supporting evidence with Echocardiogram: Clinical significant changes in pumping function of the heart.
Time frame: Days -56 and 168
This measure is known as an ejection fraction or EF.
9 secondary outcomes
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Expressive language
Time frame: Days -15, 168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Receptive language
Time frame: Days -1,168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Memory and Learning
Time frame: Days -1,168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Working Memory (WM)
Time frame: Days -1,168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Verbal Fluency (VF)
Time frame: Days -1,168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in inhibition behavior
Time frame: Days -1,168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in mental flexibility
Time frame: Days -1,84,168 and 252
Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Visual-spatial Process
Time frame: Days -1,168 and 252
Functional Outcome Measure : IDD-CHILD Vineland Adaptive Behavior Scales Scale Parent/Caregiver Interview Form, Second Edition (VABS-II)(Vineland™-II survey version)
Time frame: Days -1,168 and 252
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 Jun 2021.
- Background: PubMed 16876833Nagle DG, Ferreira D, Zhou YD. Epigallocatechin-3-gallate (EGCG): chemical and biomedical perspectives. Phytochemistry. 2006 Sep;67(17):1849-55. doi: 10.1016/j.phytochem.2006.06.020. Epub 2006 Jul 31.
- Background: PubMed 19636252Megarbane A, Ravel A, Mircher C, Sturtz F, Grattau Y, Rethore MO, Delabar JM, Mobley WC. The 50th anniversary of the discovery of trisomy 21: the past, present, and future of research and treatment of Down syndrome. Genet Med. 2009 Sep;11(9):611-6. doi: 10.1097/GIM.0b013e3181b2e34c.
- Background: PubMed 21381186Khoshnood B, Greenlees R, Loane M, Dolk H; EUROCAT Project Management Committee; EUROCAT Working Group. Paper 2: EUROCAT public health indicators for congenital anomalies in Europe. Birth Defects Res A Clin Mol Teratol. 2011 Mar;91 Suppl 1(Suppl 1):S16-22. doi: 10.1002/bdra.20776. Epub 2011 Mar 4.
- Background: PubMed 16967345Vicari S, Carlesimo GA. Short-term memory deficits are not uniform in Down and Williams syndromes. Neuropsychol Rev. 2006 Jun;16(2):87-94. doi: 10.1007/s11065-006-9008-4. Epub 2006 Aug 9.
- Background: PubMed 17237124Ronan A, Fagan K, Christie L, Conroy J, Nowak NJ, Turner G. Familial 4.3 Mb duplication of 21q22 sheds new light on the Down syndrome critical region. J Med Genet. 2007 Jul;44(7):448-51. doi: 10.1136/jmg.2006.047373. Epub 2007 Jan 19.
- Background: PubMed 17145134Dowjat WK, Adayev T, Kuchna I, Nowicki K, Palminiello S, Hwang YW, Wegiel J. Trisomy-driven overexpression of DYRK1A kinase in the brain of subjects with Down syndrome. Neurosci Lett. 2007 Feb 8;413(1):77-81. doi: 10.1016/j.neulet.2006.11.026. Epub 2006 Dec 4.
- Background: PubMed 11555628Altafaj X, Dierssen M, Baamonde C, Marti E, Visa J, Guimera J, Oset M, Gonzalez JR, Florez J, Fillat C, Estivill X. Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome. Hum Mol Genet. 2001 Sep 1;10(18):1915-23. doi: 10.1093/hmg/10.18.1915.
- Background: PubMed 17663443Belichenko PV, Kleschevnikov AM, Salehi A, Epstein CJ, Mobley WC. Synaptic and cognitive abnormalities in mouse models of Down syndrome: exploring genotype-phenotype relationships. J Comp Neurol. 2007 Oct 1;504(4):329-45. doi: 10.1002/cne.21433.
- Background: PubMed 23165261Dierssen M. Down syndrome: the brain in trisomic mode. Nat Rev Neurosci. 2012 Dec;13(12):844-58. doi: 10.1038/nrn3314.
- Background: PubMed 25944381Ji J, Lee H, Argiropoulos B, Dorrani N, Mann J, Martinez-Agosto JA, Gomez-Ospina N, Gallant N, Bernstein JA, Hudgins L, Slattery L, Isidor B, Le Caignec C, David A, Obersztyn E, Wisniowiecka-Kowalnik B, Fox M, Deignan JL, Vilain E, Hendricks E, Horton Harr M, Noon SE, Jackson JR, Wilkens A, Mirzaa G, Salamon N, Abramson J, Zackai EH, Krantz I, Innes AM, Nelson SF, Grody WW, Quintero-Rivera F. DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies. Eur J Hum Genet. 2015 Nov;23(11):1473-81. doi: 10.1038/ejhg.2015.71. Epub 2015 May 6.
- Background: PubMed 16137572Benavides-Piccione R, Dierssen M, Ballesteros-Yanez I, Martinez de Lagran M, Arbones ML, Fotaki V, DeFelipe J, Elston GN. Alterations in the phenotype of neocortical pyramidal cells in the Dyrk1A+/- mouse. Neurobiol Dis. 2005 Oct;20(1):115-22. doi: 10.1016/j.nbd.2005.02.004.
- Background: PubMed 25461715Pujol J, del Hoyo L, Blanco-Hinojo L, de Sola S, Macia D, Martinez-Vilavella G, Amor M, Deus J, Rodriguez J, Farre M, Dierssen M, de la Torre R. Anomalous brain functional connectivity contributing to poor adaptive behavior in Down syndrome. Cortex. 2015 Mar;64:148-56. doi: 10.1016/j.cortex.2014.10.012. Epub 2014 Oct 28.
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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 study testing EGCG FontUp in people with Down Syndrome and Fragile X Syndrome, 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 8 inclusion and 15 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 Jun 2021. 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.
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?
Safety Outcome Measure : Adverse Events (time frame: From day -5 to day 252 (through study completion)). The study lists 8 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 NCT03624556, which also lists 20 linked publications.
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 Jun 2021.