Understanding the Effects of Pulmonary Arterial Hypertension on Lean Muscle Mass

Overview

Patients with pulmonary arterial hypertension (PAH) are at increased risk of muscle loss and decreased physical activity. This study will aim to (1) understand the way in which muscle loss occurs in PAH, particularly the role of fat surrounding the heart, and (2) look at the impact muscle loss has on quality of life, daily physical activity, and hospitalizations in patients with PAH. The findings from this study could help identify potentially treatable factors that may improve the overall quality of life and physical functioning of patients with PAH. Subjects will be asked to attend a baseline visit where the following will be performed: * Measure your vital signs * Undergo a research blood draw, less than 4 tablespoons * Provide a urine pregnancy test (if applicable) * Review demographics, personal history, and medical history * Review current PAH medications * Complete questionnaires on how your PAH affects you * Complete a test of physical performance * Complete a grip strength test * Undergo an echocardiogram (Echo) * Complete a six-minute walk test * Undergo a Chest CT Scan * Undergo a scan of your body composition (DXA scan) * Obtain a weight and body composition measurement on the InBody Scale Subjects will also complete activity moniotring, two 24-hour diet recalls, and participate in remote follow-up visits every 6 months

Detailed description

In a subset of patients, after obtaining informed consent, patients will be scheduled for an in-person visit with a physical therapist. The subject will have their vital signs checked, blood drawn and then will have the PortaMon device applied to their biceps and their calf muscles. The PortaMon is a wireless NIRS device designed to measure muscle oxygenation non-invasively. It has one channel to measure absolute oxygenated hemoglobin and three channels to measure relative concentrations of oxy-, deoxy-, total hemoglobin concentration changes, and tissue saturation index. Following application and activation of the biosensor and the NIRS device, the physical therapist will demonstrate the exercises to the participant and will observe them performing the exercises. After the conclusion of the session (\~1.5 hours), the subject's vital signs will be reassessed and blood drawn. The second study visit will be at Week 12.

Interventions

• Diagnostic test blood draw
  Research blood draw
• Diagnostic test Short Performance Physical Battery
  test of physical performance, which involves measuring movement from sitting to standing, walking speed, and balance
• Diagnostic test Grip strength test
  Measures grip strength
• Diagnostic test Six minute walk test
  Measures distance walked in 6 minutes
• Radiation Chest CT scan
  X-ray and computer technology takes detailed pictures of the organs and structures inside your chest
• Radiation Dual-Energy X-ray Absorptiometry Scan
  Uses X-ray technology to measure the mineral density of your bones, and provides a ratio of fat tissue to lean mass (muscle) and bone
• Behavioral Activity monitoring
  A device worn on your non-dominant wrist which measures motion/ movement/ activity
• Behavioral 24 hour diet recall
  A research dietitian will contact you and ask you to provide details of what you ate over the previous 24 hours
• Diagnostic test Echocardiogram
  Ultrasound technology to create moving images of your heart, valves, and chambers
• Behavioral Quality of Life Questionnaire (emPHasis 10)
  The emPHasis-10 is a pulmonary hypertension-specific questionnaire which is scored from 0-50 (with higher scores indicating worse quality of life.)

Primary outcome measures

• Intake of food and nutrients [Time frame: One time at Baseline]
• Epicardial adipose tissue (EAT) volume [Time frame: One time at Baseline]
• Metabolomics [Time frame: One time at Baseline]
• Right ventricular (RV) function [Time frame: One time at Baseline]
• Adiponectin [Time frame: One time at Baseline]
• Low lean mass [Time frame: One time at Baseline]
• Accelerometry measures [Time frame: One time at Baseline]
• Health-Related Quality of Life (HRQOL) [Time frame: One time at Baseline]
• Measurement of adiponectin levels pre- and post-exercise at baseline and at Week 12 [Time frame: 12 Weeks]
• Measurement of oxyhemoglobin and deoxyhemoglobin concentration pre and post- exercise at baseline and Week 12. Measurement of time to recovery of oxyhemglobin post-exercise at baseline and at Week 12. [Time frame: 12 weeks]

Secondary outcome measures (1)

• Chest Computed Tomographic (CT) scan [Time frame: One time at Baseline]

Eligibility criteria

Inclusion criteria

• Signed informed consent prior to initiation of any study mandated procedure.
• Diagnosis of PAH belonging to one of the following subgroups of Group 1 PH according to the updated clinical classification \[Humbert 2022\]

• Idiopathic (IPAH)
• Heritable (HPAH)
• Drugs or toxins induced
• Associated (APAH) with one of the following:

• Connective tissue disease;
• Human immunodeficiency virus (HIV) infection;
• Congenital heart disease; or
• Portopulmonary hypertension
• Diagnosis of PAH within 6 months of enrollment or diagnosis of PAH and on stable therapy for 3 months prior to enrollment
• Documented hemodynamic diagnosis of PAH by right heart catheterization (RHC), prior to enrollment showing:

• mPAP > 20 mmHg; and
• PAWP or LVEDP ≤ 15 mmHg
• PVR > 2 Wood units

Exclusion criteria

• Prior to enrollment, evidence of moderately severe obstructive ventilator defect with:

• FEV1/FVC ≤ 5th percentile; and
• FEV1 z-score < 2.5
• Prior to enrollment, evidence of severe restrictive defect with

• TLC < 5th percentile
• FEV1 z-score < 4
• Prior to enrollment, hospitalization (within 1 week) for decompensated right heart failure
• More than moderate aortic or mitral valve disease
• LVEF < 40% within 1 year of screening
• Pregnancy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Pennsylvania Hospital — Philadelphia

Identifiers

NCT: NCT07132788 · 856202 · R01HL173533

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗