Assessment of the TGF-beta Pathway and Micro-RNA in Pediatric Pulmonary Arterial Hypertension
试验速览
- 阶段
- 不适用
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Plasma levels of BMP proteins of the TGF-β pathway
研究概览
简要总结
This is a prospective pilot study to assess the plasma levels of particular proteins involved in the transforming growth factor beta (TGF-β) pathway and its down stream regulators, CHIP, as well as micro RNA molecules in subjects with pulmonary arterial hypertension (PAH) and compare them to control subjects without PAH to see if they can be used as a diagnostic or prognostic marker of PAH and how this compares to other diagnostic biomarkers N-terminal pro-natriuretic peptide (NT Pro-BNP) and C-reactive protein (CRP).
详细描述
Aim 1: This study will correlate proteins in the TGF- β signaling pathway and micro RNA levels with invasive (catheterization) and non-invasive (echocardiography) measurements of pulmonary artery pressures to assess for the presence and severity of PAH and compare these measurements to the established biomarkers of NT Pro BNP and CRP levels.
Hypothesis 1: Plasma levels of proteins of the TGF-β pathway; bone morphogenic protein (BMP) 2, 4, 6, 7, 9 and 10 along with activin A and TGF-β1 protein as well as CHIP (carboxyl-terminus of Hsp70-intracting protein), an enzyme that regulates the activations and exports of TGF- β to the nucleus will be significantly different in subjects with PH over control subjects.
Hypothesis 2: Plasma levels of proteins in the TGF- β pathway; BMP 2, 4, 6, 7, 9 and 10 along with activin A and TGF-β1 protein as well as CHIP will show better correlation with the presence of PAH and its severity than NT-Pro BNP and CRP levels.
Hypothesis 3: The micro-RNA profiles in plasma will be significantly different in subjects with PAHPH over control subjects.
Aim 2: To correlate protein/micro-RNA levels with clinical status in PAH subjects as assessed by functional status, exercise testing, and PAH drug regimen to determine if they can correlate with disease severity.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pediatric subjects ages 2-17 years
- •Subjects undergoing a clinically indicated cardiac catheterization.
- •Subjects with proven or being evaluated for pulmonary hypertension in WHO classification group 1 or 3†
- •Subjects will be categorized as PAH subjects if they meet the hemodynamic criteria: pulmonary artery pressure >20mmHg, pulmonary vascular resistance index >3 Woods units*m2, and wedge pressures <15mmHg.
- •Subjects can be categorized as control subjects if they do not have PH on catheterization and do not meet any exclusion criteria.
排除标准
- 未提供
结局指标
主要结局
Plasma levels of BMP proteins of the TGF-β pathway
时间窗: One day
bone morphogenic protein (BMP) 2, 4, 6, 7, 9 and 10 levels will be obtained in PH subjects and will be compared to control subjects in effort to describe how those levels are different in subjects with PH over control subjects. All measured amounts of proteins will be in pg/ml.
Plasma CHIP levels assessment in PH patients and control subjects.
时间窗: One day
CHIP (carboxyl-protein terminus of Hsp70-intracting protein) plasma levels will be obtained in PH subjects and compared to control subjects in effort to describe how those levels are different in subjects with PH over control subjects. All measured levels will be in pg/ml
Plasma Activin A and TGF-β1 level of the TGF-β pathway
时间窗: One day
Activin A and TGF-β1 plasma levels will be obtained in PH subjects and compared to control subjects in effort to describe how those levels are different in subjects with PH over control subjects. All measured amounts will be will be in pg/ml.
次要结局
- Plasma levels of proteins in the TGF- β pathway and PH disease severity(One day)
- MicroRNA levels in PH vs control subjects(One day)
- Whole exome sequence analysis in PH patients and protein/microRNA levels(One day)
- Clinical findings correlation with study proteins/microRNA(One day)
研究者
Edward Kirkpatrick
Associate Professor
Medical College of Wisconsin