Ignite Creation Date:
2024-05-06 @ 6:13 PM
Last Modification Date:
2024-10-26 @ 2:43 PM
Study NCT ID:
NCT05584722
Status:
RECRUITING
Last Update Posted:
2024-01-11
First Post:
2022-10-14
Brief Title:
Risk and Resilience in Pulmonary Arterial Hypertension and Genetically Susceptible Individuals
Sponsor:
Vanderbilt University Medical Center
Organization:
Vanderbilt University Medical Center
Study Overview
Official Title:
Risk and Resilience in Pulmonary Arterial Hypertension and Genetically Susceptible Individuals
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RARE-PAH
Brief Summary:
Pulmonary arterial hypertension PAH is a severe disease with a delayed diagnosis and markedly elevated mortality High-risk populations such as those with known genetic defects provide a unique opportunity to determine the features of susceptibility and resilience to PAH This proposal will fundamentally overturn the prevailing understanding of PAH by creating molecularly-driven signatures of susceptibility and resilience provide novel insight into disease severity and potentially identify new therapeutic targets
Funding Source - FDA OOPD
Funding Source - FDA OOPD
Detailed Description:
Pulmonary arterial hypertension PAH is an orphan disease with a delayed diagnosis and markedly elevated mortality from right heart failure Despite nearly a dozen FDA-approved drugs for PAH median survival is only seven years All approved therapies target one of three vasodilatory pathways and none are disease modifying This study has two objectives 1 Understand dynamic and static relationships between molecular markers and PAH progression and resilience 2 Identify molecular features of PAH risk and resilience in individuals harboring a PAH-causing mutation It is unknown why some at risk individuals develop PAH and others do not BMPR2 mutations are present in about 30 of patients with PAH but clinical penetrance is only 20 Unaffected BMPR2 mutation carriers UMCs are a unique and understudied population that may also provide clues to disease trajectory in patients with clinical PAH Longitudinal natural history studies with molecular profiling in PAH are lacking Most molecular profiling studies in PAH are cross-sectional which limits understanding of how disease progression and disease markers relate over time The Investigators propose a strategy of dense clinical and molecular phenotyping at multiple timepoints to overcome inferential limitations of cross-sectional studies This application will leverage the clinical and research infrastructure built at Vanderbilt over the past 35 years in our study of PAH patients The investigators share an extensive published record of recruiting patients with this rare disease and related UMCs The Investigators hypothesize that a comprehensive understanding of risk and resilience over time in patients and genetically susceptible individuals will provide insight into disease severity and identify novel therapeutic targets in patients with PAH Aim 1 will identify static and dynamic molecular features of disease progression and resilience 1a Perform serial clinical proteomic and gene expression profiling in HPAH IPAH and healthy controls 3 times over 4 years Bioinformatic and network medicine analyses will identify proteins and RNAs associated with changes in clinical outcomes functional capacity and RV function in the parent cohort and two external validation cohorts1b Test whether adding molecular riskresilience markers will improve the performance of a widely used PAH risk prediction tool REVEAL 20 Risk Score Aim 2 will identify the clinical and molecular factors that promote resilience and susceptibility to PAH in a longitudinal cohort of UMCs UMCs will undergo serial clinical and molecular phenotyping as in Aim 1 Proteinsgenes that mirror PAH are risk factors and those that mirror a healthy population are resilience factors Explanatory models will be developed and tested in validation cohorts The Investigators will test UMC risk and resilience features for associations with clinical outcomes in PAH patients and risk prediction performance These studies will identify signatures of risk and resilience to PAH progression and penetrance offering an initial step toward personalizing care and surveillance guided by biologic data
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 1R01FD007627 | FDA | None | httpsreporternihgovquickSearch1R01FD007627 |