Risk and Resilience in Pulmonary Arterial Hypertension and Genetically Susceptible Individuals

NCT05584722 | Recruiting DMC

• 2 other identifiers: 2214371R01FD007627
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

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

Conditions

Idiopathic Pulmonary Arterial Hypertension; Heritable Pulmonary Arterial Hypertension; Unaffected Mutation Carriers: Healthy Participants With a Known BMPR2 Gene Mutation and Normal Pulmonary Pressure and RV Function on Echo; Healthy Individuals With no Cardiopulmonary Disease

Keywords

pulmonary hypertension

Outcome Measures

Primary Outcomes (15)

• Change in Quality of Life as measured by the emPHasis-10

  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.

  Baseline to 32 months

• Change in Quality of Life as measured by the Pediatric Quality of Life Inventory Version 4.0

  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.

  Baseline to 32 months

• Change in meters walked in six-minute walk distance (meters)

  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.

  Baseline to 32 months

• Change in diffusing capacity for carbon monoxide (DLCO) on the Pulmonary Function Test

  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

• Change in Tricuspid Annular Plane Systolic Excursion (TAPSE), expressed in mm.

  Change from baseline in Tricuspid Annular Plane systolic Excursion (TAPSE) expressed in mm on echocardiogram results at 12-16 months and 24-32 months.

  Baseline to 32 months

• Change in Tricuspid Annular Velocity (S'), as assessed by echocardiogram results, expressed in cm/sec

  Change from baseline in Tricuspid Annular Velocity (S') on echocardiogram results at 12-16 months and 24-32 months and expressed in cm/sec.

  Baseline to 32 months

• Change in Estimated Right Ventricle (RV) Systolic Pressure, as assessed by echocardiogram results, expressed in mmHg

  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.

  Baseline to 32 months

• Change in Right Ventricle (RV) Free Wall Longitudinal Strain, as assessed by echocardiogram results, and expressed as percent (%) change in myocardial deformation.

  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.

  Baseline to 32 months

• Change in Daily Step Count as measured by the mHealth device mean daily step count

  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.

  Baseline to 32 months

• Change in Resting Heart Rate (beats per minute)

  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.

  Baseline to 32 months

• Intensity of activity

  Intensity of activity is categorized as rest, light, moderate, and vigorous based on calculated metabolic equivalents.

  Baseline to 32 months

• Number of patients with a PAH-related Hospitalization Incidence

  To assess PAH-related hospitalization incidences from baseline to 12-16 months and 24-32 months. Number of patients will be assessed.

  Baseline to 32 months

• Change in Patient Medication Regimen, as measured by percentage (%) of subjects with a change in medication regimen

  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.

  Baseline to 32 months

• Number of patients with an incidence of death

  To assess incidences of death from baseline to 12-16 months and 24-32 months. Number of patients will be assessed.

  Baseline to 32 months

• Number of patients with an incidence of lung transplantation

  To assess incidences of lung transplantation from baseline to 12-16 months and 24-32 months. Number of patients will be assessed.

  Baseline to 32 months

Study Arms (3)

Idiopathic or Heritable Pulmonary Arterial Hypertension

Patients diagnosed with pulmonary arterial hypertension, either idiopathic or heritable, 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

Eligibility Criteria

• Age: 15 Years - 80 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

We plan to collect the following samples on selected subjects: DNA, RNA, serum, and plasma

MeSH Terms

Conditions

Familial Primary Pulmonary Hypertension; Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Evan Brittain, MD

  Vanderbilt Medical Center

  PRINCIPAL INVESTIGATOR

• Anna Hemnes, MD

  Vanderbilt Medical Center

  PRINCIPAL INVESTIGATOR

• Eric Austin, MD

  Vanderbilt Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelly Burke, RN

CONTACT

(615) 343-4682; kelly.burke@vumc.org

Alisha Lindsey, RT

CONTACT

(615) 343-4682; alisha.lindsey@vumc.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: October 14, 2022
• First Posted: October 18, 2022
• Study Start: November 1, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)