Assessment of the TGF-beta Pathway and Micro-RNA in Pediatric Pulmonary Arterial Hypertension
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Medical College of Wisconsin
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Plasma levels of BMP proteins of the TGF-β pathway
Study Overview
Brief Summary
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).
Detailed Description
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.
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 2 Years to 17 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Plasma levels of BMP proteins of the TGF-β pathway
Time Frame: 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.
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
- 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)
Investigators
Edward Kirkpatrick
Associate Professor
Medical College of Wisconsin