Pulmonary Arterial HypertensionNCT04489251
Assessment of the TGF-beta Pathway and Micro-RNA in Pediatric Pulmonary Arterial Hypertension
An observational study of Pulmonary Arterial Hypertension, run by Medical College of Wisconsin at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Protein Elisa analysis, microRNA analysis, whole exome sequencing
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2020to 1 Jan 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- Child
Study population: 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.
Who may be able to join
- 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.
Who cannot join
- -
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Edward C Kirkpatrick, DO, 414-266-2380, ekirkpatrick@chw.org
Nicholas Peterson, BA, 414-266-1753, npeterson@chw.org
About this study
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).
Read the 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
- Being tested
- Protein Elisa analysis, microRNA analysis, whole exome sequencing
- Keywords
- pulmonary arterial hypertension, TGF-beta pathway, microRNA
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protein Elisa analysis, microRNA analysis, whole exome sequencingDiagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Protein Elisa analysis, microRNA analysis, 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. Receives: Diagnostic Test: Protein Elisa analysis, microRNA analysis, whole exome sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: One day
Secondary outcomes (4)
Plasma levels of proteins in the TGF- β pathway and PH disease severity
BMP 2, 4, 6, 7, 9 and 10 along with activin A and TGF-β1 protein as well as CHIP levels will be correlated with the presence of PAH and its severity and how that compares to the levels of NT-Pro BNP and CRP levels.
Measured: One day
MicroRNA levels in PH vs control subjects
The micro-RNA profiles in plasma will be compared between in subjects with PAH and control subjects.
Measured: One day
Clinical findings correlation with study proteins/microRNA
Clinical findings in PAH patients will be correlated with disease severity and study protein and micro-RNA levels.
Measured: One day
Whole exome sequence analysis in PH patients and protein/microRNA levels
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.
Measured: One day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2020
- Study start1 Jul 2020
- Primary completion1 Aug 2022 (estimated)
- Study completion1 Jan 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Edward Kirkpatrick, Medical College of Wisconsin
- Investigators
- Edward C Kirkpatrick, Principal investigator, Children's Hospital and Health System Foundation, Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04489251
- Sponsor's protocol ID
- 1492809
- Status last verified
- Nov 2021
- First submitted
- 21 Jul 2020
- Last updated
- 22 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of the TGF-beta Pathway and Micro-RNA in Pediatric Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT04489251
- Acronym / sponsor ID
- 1492809
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- pulmonary arterial hypertension, TGF-beta pathway, microRNA
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 1 Aug 2022 (estimated)
- Study completion
- 1 Jan 2023 (estimated)
- First posted
- 28 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PH subjects | – | Diagnostic Test: Protein Elisa analysis, microRNA analysis, whole exome sequencing* 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 | – | Diagnostic Test: Protein Elisa analysis, microRNA analysis, whole exome sequencing* 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. |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Age groups
- Child
- Study population
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Protein Elisa analysis, microRNA analysis, whole exome sequencingELISA 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. | Diagnostic test | Control subjects, PH subjects |
Primary outcome
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 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.
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
4 secondary outcomes
Plasma levels of proteins in the TGF- β pathway and PH disease severity
Time frame: One day
MicroRNA levels in PH vs control subjects
Time frame: One day
Clinical findings correlation with study proteins/microRNA
Time frame: One day
Whole exome sequence analysis in PH patients and protein/microRNA levels
Time frame: One day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward C Kirkpatrick principal investigator
Children's Hospital and Health System Foundation, Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pulmonary Arterial Hypertension, run by Medical College of Wisconsin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Edward C Kirkpatrick, DO (414-266-2380, ekirkpatrick@chw.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma levels of BMP proteins of the TGF-β pathway (time frame: One day). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2021.