Imprinting in Metabolic Diseases - Identifying Epigenetic Mechanisms in Human Gestational Diabetes Through Cell-free DNA
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Epigenetic profiles of parents and fetuses
研究概览
简要总结
This clinical trials aims to investigate the impact of parental metabolism during pregnancy on fetal epigenetic signatures.
The metabolic profiles of both parents will be evaluated through a blood sample collected from the father and an oral glucose tolerance test administered to the pregnant mother. Additionally, epigenetic signatures will be assessed using parental blood samples. Fetal epigenetic signatures can be identified by analyzing fetal cell-free DNA that circulates in the mother's bloodstream.
详细描述
Epigenetic patterns inherited from both parents significantly influence gene expression and disease susceptibility in their offspring, with particularly negative effects in gestational diabetes, as indicated in animal and observational studies. However, human studies are limited due to the complexity and ethical concerns of collecting samples from fetuses and newborns. Invasive fetal sampling methods carry a risk of pregnancy loss, but the discovery of fetal cell-free DNA in maternal blood has revolutionized prenatal diagnostics by providing a non-invasive alternative. Recent advancements have made it possible to use cell-free DNA analyses also for epigenetic characterizations. The primary objective of this project is to elucidate the bidirectional epigenetic interactions between maternal gestational metabolism and the fetal epigenome, with a focus on identifying and understanding the biological impacts of epigenetic modifications in both the mother and fetus. Additionally, the research seeks to uncover epigenetic biomarkers that are linked to gestational diabetes and to assess the influence of parental epigenetic marks on the fetus. It will examine how parental epigenetics and parental glucose metabolism affects these modifications, facilitating a detailed analysis of the origins and mechanisms of epigenetic transmission.
We will recruit couples between gestational weeks 24 and 28, with and without gestational diabetes, and perform metabolic characterizations. Maternal cell-free DNA (including fetal DNA), maternal nuclear DNA, and paternal nuclear and cell-free DNA will be collected for methylation analyses.
研究设计
- 研究类型
- Observational
- 观察模型
- Family Based
- 时间视角
- Cross Sectional
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
- •Pregnant women between 20 and 28 weeks of gestation
- •The father of the child is known and willing to participate in the study
- •No known underlying medical conditions in either parent
- •No fetal abnormalities detected in first-trimester screening, detailed fetal anatomy ultrasound, non-invasive prenatal testing (NIPT), or any additional prenatal examinations performed, if applicable
- •No known underlying diseases
- •Understanding and voluntary signing of a consent form before study- related examinations
排除标准
- •Age < 18 years
- •Type 1 or type 2 diabetes mellitus
- •Pharmacological treatment affecting blood glucose levels (e.g., steroids, insulin)
- •Endocrine disorders (e.g., hyperthyroidism, polycystic ovary syndrome [PCOS])
- •Current depression or other psychiatric disorders
- •Eating disorders
- •Regular use of medication during pregnancy
- •Pre-existing cardiovascular disease
- •Drug and/or alcohol abuse
- •Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m²
- •C-reactive protein > 10 mg/l
- •Transaminase elevation of 2 times the upper norm
- •No consent to be informed about incidentally discovered pathological findings
- •Any other (clinical) condition that would endanger participants safety or question scientific success according to the physicians opinion.
结局指标
主要结局
Epigenetic profiles of parents and fetuses
时间窗: Baseline
Methylation pattern of CpG sites in fathers, mothers and fetuses assessed from blood samples from the father and the mother. Genome-wide DNA methylation will be quantified as 5-methylcytosine (5mC) levels at CpG sites in maternal and paternal nuclear DNA from peripheral blood. Long-read sequencing will be used to detect genomic sequences and base modifications. Fetal DNA methylation will be assessed from fetal cell-free DNA isolated from maternal plasma using long-read sequencing. Allelic phasing will be applied to assign epigenetic modifications to parental origin. Deconvolution analysis will be used to subtract blood cell-derived epigenetic patterns and infer tissue-of-origin signals.
次要结局
- Epigenetic signatures of gestational diabetes(Baseline)
- Correlation of epigenetic signatures and glycemia(Baseline)
- Correlation of epigenetic signatures and insulin sensitivity(Baseline)
- Correlation of epigenetic signatures and insulin secretion(Baseline)
- Correlation of epigenetic signatures and lipids(Baseline)
研究者
Martin Heni
Prof. Dr. med Martin Heni
University of Ulm