Pulmonary Arterial Hypertension, Interstitial Lung Disease, Healthy Adults
Conditions
Brief summary
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.
Interventions
DRUGTreprostinil
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.
DIAGNOSTIC_TESTRight Heart Catheterization (RHC) while exercising
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.
DIAGNOSTIC_TESTOptional Muscle Biopsy
A sample of muscle tissue will be collected and analyzed for the ability of the cells to utilize oxygen.
Sponsors
United Therapeutics
Mayo Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac Output Reserve (Qc) | Baseline, approximately 35 minutes | Cardiac output reserve (Qc) is the difference between the heart's maximum output during exercise and its resting output. This was measured using the direct Fick method (L/min). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| New York Heart Association (NYHA) Functional Class | Baseline, 3-months | Participants severity of heart failure symptoms was classified according to the NHYA functional class (I-IV). Lower classifications indicate lower severity of heart failure symptoms. |
| Resting Pulmonary Vascular Resistance | Baseline; after 30 minutes of rest | Resting pulmonary vascular resistance was measured in Wood units (mm Hg/L/min) during the RHC procedure. Resting pulmonary vascular resistance is the resistance against blood flow from the pulmonary veins to the left atrium of the heart. |
| Exercise Pulmonary Vascular Resistance | Baseline; approximately 35 minutes | Exercise pulmonary vascular resistance was measured in Wood units (mm Hg/L/min) during the RHC procedure. |
| Ventilatory Efficiency (VE/VCO2) | Baseline, approximately 35 minutes | Ventilatory efficiency was assessed as a ratio between the ventilation (VE) and carbon dioxide production (VCO2) measured during the RHC procedure. VE/VCO2 evaluates how efficiently a person breathes during exercise. |
| Exercise Pulmonary Artery Pressure | Baseline; approximately 35 minutes | Exercise Pulmonary artery pressure (mmHg) was measured during the RHC procedure. Pulmonary artery pressure is the pressure within the pulmonary arteries, which transport deoxygenated blood from the right side of the heart to the lungs for oxygenation. |
| Resting Right Atrial Pressure | Baseline; after 30 minutes of rest | Resting right atrial pressure (mmHg) was measured during the RHC procedure. Right atrial pressure is a measurement that reflects the amount of blood returning to the heart and the heart's ability to pump blood into the arterial system. |
| Exercise Right Atrial Pressure | Baseline; approximately 35 minutes | Exercise right atrial pressure (mmHg) was measured during the RHC procedure. Right atrial pressure is a measurement that reflects the amount of blood returning to the heart and the heart's ability to pump blood into the arterial system. |
| Resting Pulmonary Artery Pressure | Baseline; after 30 minutes of rest | Resting pulmonary artery pressure (mmHg) was measured during the RHC procedure. Pulmonary artery pressure is the pressure within the pulmonary arteries, which transport deoxygenated blood from the right side of the heart to the lungs for oxygenation. |
Countries
United States
Participant flow
Pre-assignment details
29 subjects were consented of which 5 screen failed prior to study group assignment.
Participants by arm
| Arm | Count |
|---|---|
| PAH-ILD Patients Patients diagnosed with PAH-ILD underwent RHC while exercising, received inhaled treprostinil, and underwent an optional muscle biopsy.
Treprostinil: 30mcg (5 breaths) of inhaled treprostinil was administered during the RHC procedure and patients were initiated on outpatient inhaled treprostinil therapy for 3-months with gradual up titration to target dose as per standard clinical practice.
Right Heart Catheterization (RHC) while exercising: A procedure to measure how well or poorly your heart is pumping and to measure the pressures in the heart and lungs. A catheter was inserted into a vein and artery in order to take the measurements and this was conducted while exercising on a supine cycle ergometer. Various measurements were taken during periods of rest and exercise.
Optional Muscle Biopsy: A sample of muscle tissue were collected and analyzed for the ability of the cells to utilize oxygen. | 23 |
| Healthy Volunteers Healthy volunteers underwent RHC while exercising and an optional muscle biopsy. | 0 |
| Total | 23 |
Baseline characteristics
| Characteristic | PAH-ILD Patients | Total | Healthy Volunteers |
|---|---|---|---|
| Age, Continuous | 72.5 years STANDARD_DEVIATION 8 | 72.5 years STANDARD_DEVIATION 8 | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 18 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 5 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 5 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 17 Participants | 0 Participants |
| Region of Enrollment United States | 23 participants | 23 participants | — |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 0 Participants |
| Sex: Female, Male Male | 13 Participants | 13 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 23 |
| other Total, other adverse events | 0 / 1 | 0 / 23 |
| serious Total, serious adverse events | 0 / 1 | 0 / 23 |
Outcome results
Primary
Cardiac Output Reserve (Qc)
Cardiac output reserve (Qc) is the difference between the heart's maximum output during exercise and its resting output. This was measured using the direct Fick method (L/min).
Time frame: Baseline, approximately 35 minutes
Population: Only 1 participant was enrolled in the healthy volunteers arm. Based on the low enrollment number in the healthy volunteers arm, no data is reported for the 1 subject in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAH-ILD Patients | Cardiac Output Reserve (Qc) | Baseline | 3.3 Liters/Min | Standard Deviation 2.1 |
| PAH-ILD Patients | Cardiac Output Reserve (Qc) | Approximately 35 minutes | 3.8 Liters/Min | Standard Deviation 1.8 |
Secondary
Exercise Pulmonary Artery Pressure
Exercise Pulmonary artery pressure (mmHg) was measured during the RHC procedure. Pulmonary artery pressure is the pressure within the pulmonary arteries, which transport deoxygenated blood from the right side of the heart to the lungs for oxygenation.
Time frame: Baseline; approximately 35 minutes
Population: Only 1 participant was enrolled in the healthy volunteers arm. Based on the low enrollment number in the healthy volunteers arm, no data is reported for the 1 subject in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAH-ILD Patients | Exercise Pulmonary Artery Pressure | Baseline | 50.4 mmHg | Standard Deviation 9.3 |
| PAH-ILD Patients | Exercise Pulmonary Artery Pressure | Approximately 35 Minutes | 40.6 mmHg | Standard Deviation 9 |
Secondary
Exercise Pulmonary Vascular Resistance
Exercise pulmonary vascular resistance was measured in Wood units (mm Hg/L/min) during the RHC procedure.
Time frame: Baseline; approximately 35 minutes
Population: Only 1 participant was enrolled in the healthy volunteers arm. Based on the low enrollment number in the healthy volunteers arm, no data is reported for the 1 subject in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAH-ILD Patients | Exercise Pulmonary Vascular Resistance | Baseline | 4.3 mm Hg/L/min | Standard Deviation 2.1 |
| PAH-ILD Patients | Exercise Pulmonary Vascular Resistance | Approximately 35 minutes | 2.2 mm Hg/L/min | Standard Deviation 1.2 |
Secondary
Exercise Right Atrial Pressure
Exercise right atrial pressure (mmHg) was measured during the RHC procedure. Right atrial pressure is a measurement that reflects the amount of blood returning to the heart and the heart's ability to pump blood into the arterial system.
Time frame: Baseline; approximately 35 minutes
Population: Only 1 participant was enrolled in the healthy volunteers arm. Based on the low enrollment number in the healthy volunteers arm, no data is reported for the 1 subject in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAH-ILD Patients | Exercise Right Atrial Pressure | Baseline | 16.1 mmHg | Standard Deviation 6.3 |
| PAH-ILD Patients | Exercise Right Atrial Pressure | Approximately 35 Minutes | 12.9 mmHg | Standard Deviation 6 |
Secondary
New York Heart Association (NYHA) Functional Class
Participants severity of heart failure symptoms was classified according to the NHYA functional class (I-IV). Lower classifications indicate lower severity of heart failure symptoms.
Time frame: Baseline, 3-months
Population: Only 1 participant was enrolled in the healthy volunteers arm. Based on the low enrollment number in the healthy volunteers arm, no data is reported for the 1 subject in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PAH-ILD Patients | New York Heart Association (NYHA) Functional Class | NYHA I | 1 Participants |
| PAH-ILD Patients | New York Heart Association (NYHA) Functional Class | NYHA II | 9 Participants |
| PAH-ILD Patients | New York Heart Association (NYHA) Functional Class | NYHA III | 6 Participants |
| PAH-ILD Patients | New York Heart Association (NYHA) Functional Class | NYHA IV | 6 Participants |
Secondary
Resting Pulmonary Artery Pressure
Resting pulmonary artery pressure (mmHg) was measured during the RHC procedure. Pulmonary artery pressure is the pressure within the pulmonary arteries, which transport deoxygenated blood from the right side of the heart to the lungs for oxygenation.
Time frame: Baseline; after 30 minutes of rest
Population: Only 1 participant was enrolled in the healthy volunteers arm. Based on the low enrollment number in the healthy volunteers arm, no data is reported for the 1 subject in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAH-ILD Patients | Resting Pulmonary Artery Pressure | Baseline | 36.0 mmHg | Standard Deviation 7.3 |
| PAH-ILD Patients | Resting Pulmonary Artery Pressure | After 30 minutes of Rest | 25.1 mmHg | Standard Deviation 5.2 |
Secondary
Resting Pulmonary Vascular Resistance
Resting pulmonary vascular resistance was measured in Wood units (mm Hg/L/min) during the RHC procedure. Resting pulmonary vascular resistance is the resistance against blood flow from the pulmonary veins to the left atrium of the heart.
Time frame: Baseline; after 30 minutes of rest
Population: Only 1 participant was enrolled in the healthy volunteers arm. Based on the low enrollment number in the healthy volunteers arm, no data is reported for the 1 subject in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAH-ILD Patients | Resting Pulmonary Vascular Resistance | Baseline | 5.4 mm Hg/L/min | Standard Deviation 2.1 |
| PAH-ILD Patients | Resting Pulmonary Vascular Resistance | After 30 minutes of Rest | 3.1 mm Hg/L/min | Standard Deviation 1.4 |
Secondary
Resting Right Atrial Pressure
Resting right atrial pressure (mmHg) was measured during the RHC procedure. Right atrial pressure is a measurement that reflects the amount of blood returning to the heart and the heart's ability to pump blood into the arterial system.
Time frame: Baseline; after 30 minutes of rest
Population: Only 1 participant was enrolled in the healthy volunteers arm. Based on the low enrollment number in the healthy volunteers arm, no data is reported for the 1 subject in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAH-ILD Patients | Resting Right Atrial Pressure | Baseline | 7.9 mmHg | Standard Deviation 3.4 |
| PAH-ILD Patients | Resting Right Atrial Pressure | After 30 Minutes of Rest | 6.2 mmHg | Standard Deviation 3.1 |
Secondary
Ventilatory Efficiency (VE/VCO2)
Ventilatory efficiency was assessed as a ratio between the ventilation (VE) and carbon dioxide production (VCO2) measured during the RHC procedure. VE/VCO2 evaluates how efficiently a person breathes during exercise.
Time frame: Baseline, approximately 35 minutes
Population: Only 1 participant was enrolled in the healthy volunteers arm. Based on the low enrollment number in the healthy volunteers arm, no data is reported for the 1 subject in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAH-ILD Patients | Ventilatory Efficiency (VE/VCO2) | Baseline | 50.4 Ratio | Standard Deviation 10.6 |
| PAH-ILD Patients | Ventilatory Efficiency (VE/VCO2) | Approximately 35 Minutes | 51.2 Ratio | Standard Deviation 11.2 |