Assessment of the TGF-beta Pathway and Micro-RNA in Pediatric Pulmonary Arterial Hypertension
NCT ID: NCT04489251
Last Updated: 2021-11-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
40 participants
OBSERVATIONAL
2020-07-01
2023-01-01
Brief Summary
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Detailed Description
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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
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Keywords
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Study Design
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CASE_CONTROL
PROSPECTIVE
Study Groups
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PH subjects
* 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.
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.
Control subjects
* Pediatric subjects ages 2-17 years
* Subjects undergoing a clinically indicated cardiac catheterization.
* Subjects can be categorized as control subjects if they do not have PH on catheterization and do not meet any exclusion criteria.
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.
Interventions
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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.
Eligibility Criteria
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Inclusion Criteria
* 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.
Exclusion Criteria
2 Years
17 Years
ALL
No
Sponsors
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Medical College of Wisconsin
OTHER
Responsible Party
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Edward Kirkpatrick
Associate Professor
Principal Investigators
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Edward C Kirkpatrick
Role: PRINCIPAL_INVESTIGATOR
Children's Hospital and Health System Foundation, Wisconsin
Locations
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Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Countries
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Central Contacts
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Facility Contacts
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Edward C Kirkpatrick, DO
Role: primary
Nicholas Peterson, BA
Role: backup
Other Identifiers
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1492809
Identifier Type: -
Identifier Source: org_study_id