Understanding and Preventing the Impact of Endocrine Disruptors on the Hypothalamus-pituitary Axis in Sensitive Populations: Study of the Effects of a School and Parental Policy to Minimize Exposure to Endocrine Disruptors Among 6 and 8 Year-olds in the Wallonia-Brussels Federation and Catalunya
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- Sciensano
- 入组人数
- 700
- 试验地点
- 1
- 主要终点
- Change in urinary concentration of bisphenol A (BPA)
研究概览
简要总结
This study is part of the European Hypiend project, which aims to explore the effects of co-exposure to endocrine-disrupting chemicals (EDCs) on the function and epigenetic programming of the hypothalamic-pituitary-adrenal (HPA) axis in order to define intervention strategies to minimize exposure and its consequences on the neuroendocrine system during the perinatal and prepubertal phases. The intervention during the perinatal phase is registered under the Unique Protocol ID: 101137440 - Hypiend - Clinical study to evaluate the effectiveness of a multicomponent behavioural intervention to reduce EDC exposure during the perinatal period in women and their offspring.
The intervention presented here concerns the prepubertal phase.
The primary objective is to demonstrate that a multi-component behavioral intervention (MBI) implemented in primary schools in two different European countries over two and a half school years is effective in reducing the presence of EDCs in the urine of prepubertal children, using the Health Action Process Approach (HAPA) and the Positive Behaviour Support (PBS) models to improve the intervention and parents' knowledge of these contaminants, as well as to advance scientific knowledge.
详细描述
- BACKGROUND AND JUSTIFICATION
1.1. SCOPE AND ASSESSMENT OF CURRENT KNOWLEDGE DIRECTLY RELATED TO THE SCIENTIFIC QUESTIONS TO BE ANSWERED IN THE CLINICAL STUDY
Several epidemiological studies have identified concerning links between high endocrine-disrupting chemicals (EDCs) exposure and adverse health effects in children and adolescents. As an illustrative example, in the framework of the Human Biomonitoring for Europe (HBM4EU) project, Lange et al. (2022) analysed the risk assessment of combined exposure to anti-androgen phthalates (Di(2-ethylhexyl) phthalate (DEHP), Di-isobutyl phthalate (DiBP), Di-n-butyl phthalate (DnBP), Butyl benzyl phthalate (BBzP) and Di-isononyl phthalate (DiNP) in children (6-11 years) and adolescents (12-18 years) from various European countries. The authors reported that DnBP and DiBP were the main drivers of the increased hazard index (HI) for a phtalate mixture in a large cohort of European children and adolescents. Notably, for 63% of these subjects with HI > 1, this risk would not have been detected if chemicals had been analyzed individually, illustrating the importance of mixture risk assessments. In addition, the authors also found regional differences in exposure-related HI, with children and adolescents in eastern Europe more exposed than those in the south and west, highlighting the need to include countries with varying exposure levels for more comprehensive conclusions and tailored measures, policies and recommendations.
Various epidemiological studies suggest that increased exposure to EDCs with hormonal activity in recent decades, especially to substances with direct estrogenic activity, may contribute to the observed earlier onset of puberty in girls and boys in developed countries. In this regard, a very recent cross-sectional study of 1539 Spanish children found that higher concentrations of certain non-persistent pesticides were associated with greater probability of developing earlier puberty in both boys and girls, with this association modulated by the child's body mass index (BMI).
To the investigators' knowledge, data on interventions aimed at reducing EDC exposure in prepubertal children are scarce and inconclusive, including most of them under 100 children, with most studies including fewer than 100 children, analyzing at most two EDC families, and lacking control groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 6 Years 至 8 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For children: aged between 6 and 8 from participating schools, and their parents/legal guardians.
- •For parents/legal guardians:
- •Understanding the local languages (either French in Belgium, or Spanish/Catalan in Spain) and being able to complete forms in that language;
- •Be in possession of a smartphone. However, if participants do not have a smartphone and wish to do so, a smartphone will be made available to them for the duration of the study.
- •For schools:
- •Fewer than 5 participating children enrolled in the school.
- •Unwillingness or inability to devote sufficient time to the project.
- •For children:
- •Refusal to participate (child informed consent form not obtained); parents will be asked to discuss with the child before exclusion.
- •Parents or legal guardians do not sign the informed consent form.
- •For parents/legal guardians:
- •Refusal to participate.
- •Unwillingness to use a mobile phone as part of the project (exclusion from sample).
排除标准
- •For schools :
- •The number of participating children in the school is less than
- •Not being ready to devote time to the project.
- •For children :
- •If children do not agree to participate (ICF for children), the parents will be asked to discuss the matter with them before the child is excluded.
- •If the parents or legal guardians do not sign the informed consent.
- •For parents/legal guardians :
- •If the parents refuse to participate.
- •If the parents do not wish to use a mobile phone as part of the project, they will not be included in the sample.
研究组 & 干预措施
Information group
In this arm, the parents and schools (termed general schools) involved will receive a digital booklet about the nature and risks of endocrine-disrupting chemicals (EDCs), general information on exposure routes, and placebo workshops on the dangers of screens, the benefits of physical activity, and the importance of good sleep habits. Neither the parents nor the schools in this group will be involved in any specific intervention aimed at reducing exposure to EDCs. At the end of the project, the parents in the information group will have access to all options provided by the digital tool and to the documents produced following the workshops or the questions and answers from participants in the intervention group. The schools will receive the educational program proposed to the intervention group.
干预措施: Information (Behavioral)
Multi-Component Behavioral intervention group
The intervention is a 28-month multi-component behavioral intervention (MBI) promoting an "EDC-free culture" in schools (termed holistic schools) and families through shared values, knowledge, and behaviors to reduce exposure to endocrine-disrupting chemicals (EDCs) in daily life. Based on the Health Action Process Approach (HAPA) and Positive Behaviour Support (PBS) models, it is introduced at three levels: (1) School: implementation of plastic-free organic canteens, staff engagement, and explicit teaching of EDC-free behaviors with positive reinforcement; (2) Parents: workshops (on-site/online) and a mobile app offering personalized missions, practical guidance, and community support; (3) Children: educational activities to raise awareness and foster healthy habits.
干预措施: Multi-Component Behavioral intervention (Behavioral)
结局指标
主要结局
Change in urinary concentration of bisphenol A (BPA)
时间窗: From enrollment to the end of the intervention at 26 months
Very few studies have examined whether educational programs teaching individuals how to reduce their exposure to endocrine-disrupting chemicals can effectively lower urinary levels of these substances, particularly in children. In one study by Kim et al. (2021), sixty-two mothers with young children participated in an online program promoting healthier behaviors; after one month, most measured urinary chemical levels showed significant changes . Another study by Sessa et al. (2021) involved 130 primary-school children whose school canteen adopted plastic-free service for six months, resulting in a clear reduction in the children's urinary bisphenol A levels . Given this context, our study selects urinary bisphenol A concentration as the primary outcome. Analyses will be conducted on night-time and morning urine samples collected at four time points: at enrollment (Visit 1), after 8 months (Visit 2), after 20 months (Visit 3), and after 26 months (Visit 4).
Change in urinary concentration of BPA
时间窗: From enrollment to the end of the intervention at 26 months
Very few studies have looked at whether educational programs that teach people how to reduce their exposure to EDCs can actually lower the levels of these chemicals in urine, especially in children. In one study by Kim JH et al. (2021), 62 mothers with young children took part in an online program that encouraged healthier behaviors, and after one month, most of the chemical levels measured in their urine had changed significantly. Another study by Sessa et al. (2021) involved 130 primary-school children whose school canteen used a plastic-free service for six months; this led to a clear drop in the children's urinary Bisphenol A (BPA) levels. Given this background, our study selects urinary BPA concentration as the primary outcome.
次要结局
- Number of participants classified as at risk of precocious puberty(From enrollment to the end of the intervention at 26 months)
- Change from baseline in Body Mass Index z-score(From enrollment to the end of the intervention at 26 months)
- Change from baseline in executive function T-scores as assessed by the Behavior Rating Inventory of Executive Function parent-report questionnaire(From enrollment to the end of the intervention at 26 months)
- Number of participants in precocious puberty, as assessed by the Tanner scale and the Prepubertal Development Scale (PDS)(From enrollment to the end of the intervention at 26 months)
- Change from baseline in BMI z-score(From enrollment to the end of the intervention at 26 months)
- Change from baseline in executive function T-scores as assessed by the Behavior Rating Inventory of Executive Function (BRIEF) parent-report questionnaire(From enrollment to the end of the intervention at 26 months)