Genetics and Environment INtersection in the Amyotrophic Lateral Sclerosis - FrontoTemporal Dementia Spectrum: an Italian Twins Cohort StudY with a Multi-Omics Approach
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 3
- 主要终点
- Environmental/genetic risk/protective factors involved in driving discordance in monozygotic (MZ) twins
研究概览
简要总结
The goal of this study is to learn from discordant twins affected by Amyotrophic Lateral Sclerosis and/or Frontotemporal Dementia the contribution of genetic background versus environmental exposure. The main questions it aims to answer is:
- How far does the genetic background explain the onset of ALS/FTD in discordant twins?
- Which environmental factors and events occurring in post-fetal life influence the onset or progression of this neurodegenerative condition? Participants with ALS and/or FTD with a monozygotic or dizygotic twin willing to contribute to this research will be followed up for two years by specialized Motor Neuron Disorders centers in Italy, donating biological specimen for -omic sciences analysis, and checking out if prodromal signs/symptoms of these two conditions will develop during time.
详细描述
The main objective of the study is to develop a prospective national twins cohort and virtual biobank collecting demographic, clinical and instrumental data and biological samples of twins with ALS/FTD. Through the definition of a multi-omics profile in ALS twins the study aims to disclose the burden of environmental or genetic risk factors for ALS/FTD and ALS specific biological signatures. Secondary aims include:
- to disclose part of the heritability gap in monozygotic (MZ) discordant twins
- to assess the burden of epigenetic and transcriptomic differences between MZ discordant twins, uncovering which pathways are activated/inactivated in asymptomatic twins and may protect them from the neurodegenerative process
- to evaluate the effects of environment on the risk of developing ALS/FTD (discordant twins) and of developing different phenotypes of ALS (concordant twins). Exposure history will be related to quantification of pesticides, heavy metals and metalloids in biological samples.
- to investigate how lifetime environmental exposures affect microbiota composition and next metabolomics and immune profile
- to correlate biological signatures with clinical features and disease heterogeneity (onset, progression, survival) for discordant twins
- to correlate environmental factors exposure with biological factors as mentioned above (e.g.microbiota, immunological. factors)
- to acquire biological data over time to discriminate between changes related to disease pathogenesis and epiphenomena secondary to the disease advancement.
- to assess neurophysiological, neuropsychological and imaging signatures within the ALS-FTD spectrum of disease across discordant twins, in particular in the asymptomatic twin, in order to disclose potential presymptomatic subclinical traits. In concordant twins, the same extensive batteries will be used to evaluate whether disease progression proceeds at the same pace or affects similar or divergent neuroanatomical substrates.
Study population Being a national ALS-FTD twin cohort study, study population could include all Italian MZ and dizygotic (DZ) twins of whom at least one is affected by ALS or ALS-FTD and possibly their parents for trios studies. ALS/FTD twins will be invited from the referring neurologist to participate in the GENIALITY study and will be sent for screening and baseline visits to the nearest clinical center involved in this study, either Modena, Turin or Palermo.
Twin pairs will undergo a detailed interview, visit, clinical tests including neuropsychological testing (NPS), neuroimaging and neurophysiological studies, extensive environmental and exposure history, and blood, CSF (optional), skin, hair, saliva and stool collection.
ALS patients will be followed up by the centers with visits scheduled every 3-4 months as for clinical practice, while healthy twins will be asked to be followed with neurological evaluations every 6 months up to 24 months of the study duration.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age >18 yrs
- •Presence of MZ or DZ twins in the family both willing to participate in the study and able to provide informed consent
- •At least one twin is affected by ALS as defined by Gold Coast Criteria (Shefner et al., 2020) and/or by FTD as defined by Strong and colleagues (Strong et al., 2017)
- •Subjects able and willing to comply with study procedures as per protocol
- •Subjects able to understand, and capable of providing informed consent at screening visit before any protocol-specific procedures
排除标准
- •Unwillingness to perform assessments as stated in the protocol at least during baseline visit for both twins
- •Unwillingness to donate biological samples collected at periphery (lumbar puncture excluded) for both twins
- •Women who are pregnant or breastfeeding
结局指标
主要结局
Environmental/genetic risk/protective factors involved in driving discordance in monozygotic (MZ) twins
时间窗: 24 months
Using a multi-omic approach, the investigators will establish a longitudinal cohort of Italian twins affected by ALS/FTD, collecting various samples to compare affected and unaffected twins across multiple biological and phenotypic variables. The aim is to uncover the factors underlying discordance in monozygotic twins, identifying what protects the unaffected twins and what predisposes the affected ones.
次要结局
未报告次要终点
研究者
JESSICA MANDRIOLI
Prof
Azienda Ospedaliero-Universitaria di Modena