Pediatric Exploratory Research Study of EGCG Use and Safety (PERSEUS)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 76
- 试验地点
- 2
- 主要终点
- Safety Outcome Measure : Adverse Events
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The treatment consists in FontUp (EGCG on a dietary supplement with chocolate like shake flavor) taken dissolved in 100mL of water two times a day (breakfast and afternoon snack). The placebo treatment is the same product but without the EGCG in it, taken with the same posology.
入排标准
- 年龄范围
- 6 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
- •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.
结局指标
主要结局
Safety Outcome Measure : Adverse Events
时间窗: 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
时间窗: 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: Measure: Number of participants with treatment-related adverse events with supporting evidence with Echocardiogram: Clinical significant changes in pumping function of the heart.
时间窗: Days -56 and 168
This measure is known as an ejection fraction or EF.
Safety Outcome Measure: Number of participants with treatment-related adverse events with supporting evidence with blood analysis: Changes in thyroid function
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
时间窗: 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.
次要结局
- Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Expressive language(Days -15, 168 and 252)
- Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Receptive language(Days -1,168 and 252)
- Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Memory and Learning(Days -1,168 and 252)
- Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Verbal Fluency (VF)(Days -1,168 and 252)
- Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in inhibition behavior(Days -1,168 and 252)
- Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Working Memory (WM)(Days -1,168 and 252)
- Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in mental flexibility(Days -1,84,168 and 252)
- Cognitive Outcome Measure : IDD-CHILD Battery. Cognitive changes in Visual-spatial Process(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)(Days -1,168 and 252)
研究者
Rafael de la Torre
Director of the Neurosciences Department in Institut Hospital d'Investigacions Mèdiques (IMIM), PharmD, PhD
Parc de Salut Mar