- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05584722
Risk and Resilience in Pulmonary Arterial Hypertension and Genetically Susceptible Individuals (RARE-PAH)
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
Study Overview
Status
Detailed Description
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Kelly Burke, RN
- Phone Number: (615) 343-4682
- Email: kelly.burke@vumc.org
Study Contact Backup
- Name: Alisha Lindsey, RT
- Phone Number: (615) 343-4682
- Email: alisha.lindsey@vumc.org
Study Locations
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Tennessee
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Nashville, Tennessee, United States, 37232
- Recruiting
- Vanderbilt University Medical Center
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Contact:
- Kelly Burke, RN
- Email: kelly.burke@vumc.org
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
- Diagnosed with idiopathic or heritable, pulmonary arterial hypertension (PAH), defined according to standard criteria
- Unaffected Mutation Carriers: Healthy participants with a known BMPR2 gene mutation and normal pulmonary pressure and RV function on echo
- Healthy Controls: Healthy individuals without cardiopulmonary disease.
Description
Inclusion Criteria:
- Children and Adults, aged 15 - 80
- Diagnosed with idiopathic or heritable, pulmonary arterial hypertension (PAH), defined according to standard criteria
- Unaffected Mutation Carriers: Healthy participants with a known BMPR2 gene mutation and normal pulmonary pressure and RV function on echo
- Healthy Controls: Healthy individuals without cardiopulmonary disease.
- WHO functional class I-III
- Stable PAH-specific medication regimen for three months prior to enrollment. Subjects with only a single diuretic adjustment in the prior three months will be included. Adjustments in IV prostacyclin for side effect management are allowed.
Exclusion Criteria:
- Prohibited from normal activity due to wheelchair bound status, bed bound status, reliance on a cane/walker, activity-limiting angina, activity-limiting osteoarthritis, or other condition that limits activity.
- Pregnancy
- Diagnosis of PAH etiology other than idiopathic, heritable
- Functional class IV heart failure
- Requirement of > 2 diuretic adjustment in the prior three months.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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Idiopathic or Heritable Pulmonary Arterial Hypertension
Patients diagnosed with pulmonary arterial hypertension, either idiopathic or heritable, defined according to standard criteria.
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Unaffected Mutation Carriers
Healthy participants with a known BMPR2 gene mutation and normal pulmonary pressure and RV function on echo.
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Healthy Controls
Healthy individuals without cardiopulmonary disease
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Quality of Life as measured by the emPHasis-10
Time Frame: Baseline to 32 months
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The emPHasis-10 is a short and easy questionnaire that consists of 10 items that address breathlessness, fatigue, control, and confidence.
Each item is scored on a semantic differential six-point scale (0-5), with contrasting adjectives at each end.
A total emPHasis-10 score is derived using simple aggregation of the 10 items.
emPHasis-10 scores range from 0 to 50, higher scores indicate worse quality of life.
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Baseline to 32 months
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Change in Quality of Life as measured by the Pediatric Quality of Life Inventory Version 4.0
Time Frame: Baseline to 32 months
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The PedsQL (Pediatric Quality of Life Inventory) is a modular instrument for measuring health-related quality of life in children and adolescents ages 2 to 18.
The PedsQL 4.0 Generic Core Scales are multidimensional child self-report and parent proxy-report scales developed as the generic core measure that consists of 23 items applicable for healthy school and community populations, as well as pediatric populations with acute and chronic health conditions.
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Baseline to 32 months
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Change in meters walked in six-minute walk distance (meters)
Time Frame: Baseline to 32 months
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The 6MWT measures the distance (in meters), a participant can walk at a comfortable speed on a flat, hard surface in 6 minutes.
The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out daily physical activities.
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Baseline to 32 months
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Change in diffusing capacity for carbon monoxide (DLCO) on the Pulmonary Function Test
Time Frame: Baseline to 32 months
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Pulmonary function tests (PFTs) are noninvasive tests that show how well the lungs are working. The tests measure lung volume, capacity, rates of flow, and gas exchange. DLCO measures the quantity of carbon monoxide (CO) transferred per minute from alveolar gas to red blood cells in pulmonary capillaries and is expressed as mL/min/mm Hg. |
Baseline to 32 months
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Change in Tricuspid Annular Plane Systolic Excursion (TAPSE), expressed in mm.
Time Frame: Baseline to 32 months
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Change from baseline in Tricuspid Annular Plane systolic Excursion (TAPSE) expressed in mm on echocardiogram results at 12-16 months and 24-32 months.
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Baseline to 32 months
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Change in Tricuspid Annular Velocity (S'), as assessed by echocardiogram results, expressed in cm/sec
Time Frame: Baseline to 32 months
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Change from baseline in Tricuspid Annular Velocity (S') on echocardiogram results at 12-16 months and 24-32 months and expressed in cm/sec.
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Baseline to 32 months
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Change in Estimated Right Ventricle (RV) Systolic Pressure, as assessed by echocardiogram results, expressed in mmHg
Time Frame: Baseline to 32 months
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Change from baseline in the estimated right ventricular systolic pressure on echocardiogram results at 12-16 months and 24-32 months and expressed in mmHg.
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Baseline to 32 months
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Change in Right Ventricle (RV) Free Wall Longitudinal Strain, as assessed by echocardiogram results, and expressed as percent (%) change in myocardial deformation.
Time Frame: Baseline to 32 months
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Change from baseline in right ventricle free wall longitudinal strain on echocardiogram results at 12-16 months and 24-32 months and expressed as percent (%) change in myocardial deformation.
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Baseline to 32 months
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Change in Daily Step Count as measured by the mHealth device mean daily step count
Time Frame: Baseline to 32 months
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Change from the baseline activity monitoring period to the 12-16 month activity monitoring period to the 24-32 month activity monitoring period.
Data obtained by the mHealth device.
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Baseline to 32 months
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Change in Resting Heart Rate (beats per minute)
Time Frame: Baseline to 32 months
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Monitored regularly using activity tracking device (per second when active, per 5 seconds when inactive).
Subject's resting and peak exercise heart rate will also be recorded at baseline, 12-16 months, and 24-32 months.
Targets exercise capacity.
Heart rate is expressed as beats per minute.
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Baseline to 32 months
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Intensity of activity
Time Frame: Baseline to 32 months
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Intensity of activity is categorized as rest, light, moderate, and vigorous based on calculated metabolic equivalents.
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Baseline to 32 months
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Number of patients with a PAH-related Hospitalization Incidence
Time Frame: Baseline to 32 months
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To assess PAH-related hospitalization incidences from baseline to 12-16 months and 24-32 months.
Number of patients will be assessed.
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Baseline to 32 months
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Change in Patient Medication Regimen, as measured by percentage (%) of subjects with a change in medication regimen
Time Frame: Baseline to 32 months
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Change from baseline in patient medication regimen from baseline to 12-16 months and 24-32 months as measured by percentage (%) of subjects with a change in medication regimen.
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Baseline to 32 months
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Number of patients with an incidence of death
Time Frame: Baseline to 32 months
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To assess incidences of death from baseline to 12-16 months and 24-32 months.
Number of patients will be assessed.
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Baseline to 32 months
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Number of patients with an incidence of lung transplantation
Time Frame: Baseline to 32 months
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To assess incidences of lung transplantation from baseline to 12-16 months and 24-32 months.
Number of patients will be assessed.
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Baseline to 32 months
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Collaborators and Investigators
Investigators
- Principal Investigator: Evan Brittain, MD, Vanderbilt Medical Center
- Principal Investigator: Anna Hemnes, MD, Vanderbilt Medical Center
- Principal Investigator: Eric Austin, MD, Vanderbilt Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 221437
- 1R01FD007627 (U.S. FDA Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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