A Study of Treprostinil to Treat Interstitial Lung Disease Pulmonary Hypertension

Study Overview
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Brief Summary
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The purpose of this research study is to find out more about the drug treprostinil via inhaler and the mechanisms of why patients with pulmonary arterial hypertension related to Interstitial Lung disease (PAH-ILD) have limitations during exercise. The investigator is studying treprostinil's effect on patients with PAH-ILD during exercise and its effect on their quality of life after using it for 3 months.

Official Title
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Comprehensive O2 Transfer Analysis From the Lung to Mitochondria of Inhaled Treprostinil in Interstitial Lung Disease Pulmonary Hypertension

Conditions
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Pulmonary Arterial Hypertension, Interstitial Lung Disease, Healthy Adults

Intervention / Treatment
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* Drug: Treprostinil
* Diagnostic Test: Right Heart Catheterization (RHC) while exercising
* Diagnostic Test: Optional Muscle Biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Pulmonary Arterial Hypertension due to Interstitial Lung Disease (ILD-PAH) being considered for inhaled treprostinil Resting right heart catheterization with mean pulmonary artery pressure >20 mmHg and PVR> 3 Wood units Healthy volunteers will have no known lung disease, heart failure, muscular disease or pulmonary hypertension, no bleeding abnormalities, and have the ability to exercise. Exclusion Criteria: Inability to exercise Females who are pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Healthy Volunteers<br>Healthy volunteers will undergo RHC while exercising and an optional muscle biopsy. | Diagnostic Test: Right Heart Catheterization (RHC) while exercising<br>* A procedure to measure how well or poorly your heart is pumping and to measure the pressures in the heart and lungs. A catheter will be inserted into a vein and artery in order to take the measurements and this will be conducted while exercising on a supine cycle ergometer. Various measurements will be taken during periods of rest and exercise.<br>Diagnostic Test: Optional Muscle Biopsy<br>* A sample of muscle tissue will be collected and analyzed for the ability of the cells to utilize oxygen.<br>|
| Experimental: PAH-ILD Patients<br>Patients diagnosed with PAH-ILD will undergo RHC while exercising, receive inhaled treprostinil, and undergo an optional muscle biopsy. | Drug: Treprostinil<br>* 30mcg (5 breaths) of inhaled treprostinil will be administered during the RHC procedure and patients will be initiated on outpatient inhaled treprostinil therapy for 3-months with gradual up titration to target dose as per standard clinical practice.<br>Diagnostic Test: Right Heart Catheterization (RHC) while exercising<br>* A procedure to measure how well or poorly your heart is pumping and to measure the pressures in the heart and lungs. A catheter will be inserted into a vein and artery in order to take the measurements and this will be conducted while exercising on a supine cycle ergometer. Various measurements will be taken during periods of rest and exercise.<br>Diagnostic Test: Optional Muscle Biopsy<br>* A sample of muscle tissue will be collected and analyzed for the ability of the cells to utilize oxygen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardiac output reserve (Qc) | Cardiac output reserve (Qc) will be measured using the direct Fick method (L/min) during the RHC procedure. | Baseline, approximately 35 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ventilatory efficiency (VE/VCO2) | Ventilatory efficiency will be assessed as a ratio between the ventilation (VE) and carbon dioxide production (VCO2) measured during the RHC procedure. | Baseline, approximately 35 minutes | 
| Change in New York Heart Association (NYHA) functional class | Patients severity of heart failure symptoms will be classified according to the NHYA functional class (I-IV). Lower classifications indicate lower severity of heart failure symptoms. | Baseline, 3-months | 
| Change in resting pulmonary vascular resistance | Resting pulmonary vascular resistance will be measured in Wood units (mm Hg/L/min) during the RHC procedure | Baseline; after 30 minutes of rest | 
| Change in exercise pulmonary vascular resistance | Exercise pulmonary vascular resistance will be measured in Wood units (mm Hg/L/min) during the RHC procedure | Baseline; approximately 35 minutes | 
| Change in resting pulmonary artery pressure | Resting pulmonary artery pressure (mmHg) will be measured during the RHC procedure | Baseline; after 30 minutes of rest | 
| Change in exercise pulmonary artery pressure | Exercise Pulmonary artery pressure (mmHg) will be measured during the RHC procedure | Baseline; approximately 35 minutes | 
| Change in resting right atrial pressure | Resting right atrial pressure (mmHg) will be measured during the RHC procedure | Baseline; after 30 minutes of rest | 
| Change in exercise right atrial pressure | Exercise right atrial pressure (mmHg) will be measured during the RHC procedure | Baseline; approximately 35 minutes |