NCT04489251

Assessment of the TGF-beta Pathway and Micro-RNA in Pediatric Pulmonary Arterial Hypertension

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 40 (estimated)
• Sponsor: Medical College of Wisconsin · Academic / Other
• Sex: All
• Age: 2 Years – 17 Years
• Healthy volunteers: —

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. Hypothesis 1: Clinical findings in PAH patients will correlate with disease severity and study proteins and micro-RNA levels better than established biomarkers. Aim 3: To correlate evidence of genetic abnormalities through whole exome sequencing especially in regions known or suspected to cause PAH (e.g. BMPR2, ENG, and ALK1 mutations), within the TGF-β pathway or lung development with the tested protein/micro-RNA levels. Hypothesis 1: Genetic evaluation of patients with PAH will show abnormalities within the TGF-β pathway or lung development.

Conditions

• Pulmonary Arterial Hypertension

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Protein Elisa analysis, microRNA analysis, whole exome sequencing	ELISA Testing Procedure: The circulating levels of BMP 2, 4, 6, 7, 9 and 10, together with activin A and TGF-β as well as CHIP will be measured using streptavidin ELISA assays. Micro-RNA analysis: From 100µL of plasma, we will prepare small RNA libraries using TruSeq Small RNA Sample Preparation kit (Illumina Inc). TGF-B mutation evaluation: Blood from subjects with PH will also be analyzed for known genetic mutations in TGF-B pathway using whole exome sequencing.

Timeline

• Start date: 2020-07-01
• Primary completion: 2022-08-01
• Completion: 2023-01-01
• First posted: 2020-07-28
• Last updated: 2021-11-22

Locations

1 site across 1 country: United States