NCT05584722 · Vanderbilt University Medical Center
Risk and Resilience in Pulmonary Arterial Hypertension and Genetically Susceptible Individuals
(RARE-PAH)
What this study is about
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.
View original scientific description
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.
Primary outcome measures
Change in Quality of Life as measured by the emPHasis-10
Time frame: Baseline to 32 months
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.
Change in Quality of Life as measured by the Pediatric Quality of Life Inventory Version 4.0
Time frame: Baseline to 32 months
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.
Change in meters walked in six-minute walk distance (meters)
Time frame: Baseline to 32 months
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.
Change in diffusing capacity for carbon monoxide (DLCO) on the Pulmonary Function Test
Time frame: Baseline to 32 months
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.
Change in Tricuspid Annular Plane Systolic Excursion (TAPSE), expressed in mm.
Time frame: Baseline to 32 months
Change from baseline in Tricuspid Annular Plane systolic Excursion (TAPSE) expressed in mm on echocardiogram results at 12-16 months and 24-32 months.
Change in Tricuspid Annular Velocity (S'), as assessed by echocardiogram results, expressed in cm/sec
Time frame: Baseline to 32 months
Change from baseline in Tricuspid Annular Velocity (S') on echocardiogram results at 12-16 months and 24-32 months and expressed in cm/sec.
Change in Estimated Right Ventricle (RV) Systolic Pressure, as assessed by echocardiogram results, expressed in mmHg
Time frame: Baseline to 32 months
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.
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
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.
Change in Daily Step Count as measured by the mHealth device mean daily step count
Time frame: Baseline to 32 months
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.
Change in Resting Heart Rate (beats per minute)
Time frame: Baseline to 32 months
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.
Intensity of activity
Time frame: Baseline to 32 months
Intensity of activity is categorized as rest, light, moderate, and vigorous based on calculated metabolic equivalents.
Number of patients with a PAH-related Hospitalization Incidence
Time frame: Baseline to 32 months
To assess PAH-related hospitalization incidences from baseline to 12-16 months and 24-32 months. Number of patients will be assessed.
Change in Patient Medication Regimen, as measured by percentage (%) of subjects with a change in medication regimen
Time frame: Baseline to 32 months
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.
Number of patients with an incidence of death
Time frame: Baseline to 32 months
To assess incidences of death from baseline to 12-16 months and 24-32 months. Number of patients will be assessed.
Number of patients with an incidence of lung transplantation
Time frame: Baseline to 32 months
To assess incidences of lung transplantation from baseline to 12-16 months and 24-32 months. Number of patients will be assessed.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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.
- Diagnosis of PAH etiology other than idiopathic, heritable
- Functional class IV heart failure
- Requirement of \> 2 diuretic adjustment in the prior three months.
Where
- Nashville, Tennessee
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 10, 2026 · Source of record for eligibility and locations