Assessment of the TGF-beta Pathway and Micro-RNA in Pediatric Pulmonary Arterial Hypertension
1 other identifier
observational
40
1 country
1
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for all trials
Started Jul 2020
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2020
CompletedFirst Submitted
Initial submission to the registry
July 21, 2020
CompletedFirst Posted
Study publicly available on registry
July 28, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2023
CompletedNovember 22, 2021
November 1, 2021
2.1 years
July 21, 2020
November 12, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Plasma levels of BMP proteins of the TGF-β pathway
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.
One day
Plasma Activin A and TGF-β1 level of the TGF-β pathway
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.
One day
Plasma CHIP levels assessment in PH patients and control subjects.
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
One day
Secondary Outcomes (4)
Plasma levels of proteins in the TGF- β pathway and PH disease severity
One day
MicroRNA levels in PH vs control subjects
One day
Clinical findings correlation with study proteins/microRNA
One day
Whole exome sequence analysis in PH patients and protein/microRNA levels
One day
Study Arms (2)
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.
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.
Interventions
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
Subjects with previously confirmed or suspected to have pulmonary arterial hypertension (PAH) that are undergoing a clinically indicated cardiac catheterization (for diagnostic evaluation) ages 2-17 years are eligible for participation. Control subjects undergoing a catheterization as part of an intervention such as atrial septal defect closure or patent ductus arteriosus closure and have a routine right heart catheterization as a part of that procedure and meet inclusion criteria.
You may qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Biospecimen
Serum is obtained from the pulmonary artery in patients undergoing a cardiac catheterization.
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Edward C Kirkpatrick
Children's Hospital and Health System Foundation, Wisconsin
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor
Study Record Dates
First Submitted
July 21, 2020
First Posted
July 28, 2020
Study Start
July 1, 2020
Primary Completion
August 1, 2022
Study Completion
January 1, 2023
Last Updated
November 22, 2021
Record last verified: 2021-11
Data Sharing
- IPD Sharing
- Will not share