COPD
Conditions
Brief summary
The purpose of this study is to determine whether the new inhaler, Bevespi improves lung function. Magnetic resonance imaging (MRI) using inhaled hyperpolarized 129Xe gas, that can provide useful images of the functioning of the lung will be used as a new measure to determine change in function. The investigator anticipate these images will provide more specific information about lung disease than standard lung function tests in response to treatment.
Detailed description
The study will characterize ventilation and gas transfer distributions in GOLD II and III COPD patients and assess the potential for these physiological parameters as a novel phenotyping method using Magnetic resonance imaging (MRI) using inhaled hyperpolarized 129Xe gas. The study will additionally quantify regional ventilation and gas transfer response to glycopyrrolate/formoterol in GOLD II and III COPD patients.
Interventions
DRUGhyperpolarized 129Xe gas MRI
There will be MRI imaging before the treatment with Bevespi and another one 2 weeks after use Bevespi. Images obtained using 129Xe MRI will be compared with standard lung function tests that are used routinely in the clinic, 6 minute walk test that assesses walking ability and several questionnaires that assess shortness of breath and life quality.
DRUGBevespi Aerosphere
There will be MRI imaging before the treatment with Bevespi and another one 2 weeks after use Bevespi.
Sponsors
Bastiaan Driehuys
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of COPD confirmed by post-bronchodilator spirometry demonstrating (forced expiratory volume at 1 second(FEV1)/forced vital capacity (FVC) \< 0.70 and forced expiratory volume at 1 second (FEV1) in GOLD 2 or 3 stage (30%≤ (forced expiratory volume at 1 second \[FEV1\] \< 80%) * Willing and able to give informed consent and adhere to visit/protocol schedules * Women of childbearing potential must have a negative urine pregnancy test
Exclusion criteria
* Upper respiratory tract infection within 6 weeks * Chronic systemic corticosteroid use \> 10 mg/day of prednisone * Chronic oxygen use (intermittent or continuous) * Previous lung resection surgery or decortication * Previous history of pneumothorax * Evidence of interstitial, occupational or chronic infectious lung disease by imaging studies * History of exposure to occupational or environmental hazards that are known to cause lung diseases * For women of child bearing potential, positive pregnancy test * Major chronic illnesses which in the judgement of the study physician would interfere with participation in the study * Patients who are not willing to withhold COPD inhalers for the run-in period. * MRI is contraindicated based on responses to MRI screening questionnaire * Subject is pregnant or lactating * Respiratory illness of a bacterial or viral etiology within 30 days of MRI * Subject has any form of known cardiac arrhythmia * Subject does not fit into 129Xe vest coil used for MRI * Subject cannot hold his/her breath for 15 seconds * Subject deemed unlikely to be able to comply with instructions during imaging
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ventilation Distribution as Measured by Ventilation Defect+Low Percent | Week 2 | The ventilation distribution as measured by ventilation defect+low percent is to measure the area of the lung that has no air. |
| Barrier Uptake. | 2 weeks | Diffusion of Xe gas across the lung membrane into the blood. This measures how well oxygen goes through the lung into the blood. |
| Red Blood Cell (RBC) Uptake | 2 weeks | Amount of Xe gas that enters the blood stream after it diffuses across the lung membrane |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary Function Test - Residual Volume (RV) | 2 weeks | Residual volume (RV) is the volume of air remaining in the lungs after a maximal exhalation. |
| Pulmonary Function Test - Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) | 2 weeks | DLCO measures the ability of oxygen to travel from the air sacs of the lungs to the blood stream. |
| 6-minute Walk Test (6MWT) | 2 weeks | The 6-minute walk test (6MWT) measures the distance walked at a natural pace for 6 minutes. |
| Pulmonary Function Test - Forced Vital Capacity (FVC) | 2 weeks | Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible, as measured by spirometry. |
| Rating of Perceived Dyspnea (RPD) Scale | 2 weeks | A patient reported outcome to measure perceived exertion during physical activity. The RPD scale goes from 0 to 10, where 0 = no shortness of breath at all and 10 = maximal shortness of breath (needing to stop the exercise or activity). |
| COPD Assessment Test (CAT) Score | 2 weeks | Functional measurement for COPD patients. Range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD on a patient's life. |
| St. George's Respiratory Questionnaire (SGRQ) Score | 2 weeks | The SGRQ is used to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations. |
| Pulmonary Function Test - Forced Expiratory Volume-one Second (FEV1) | 2 weeks | FEV1 is a lung airflow measure to assess the amount of air that can be blown out in one second. |
| Pulmonary Function Test - Total Lung Capacity (TLC) | 2 weeks | Total Lung Capacity (TLC) is the volume in the lungs at a maximal inhalation. |
Countries
United States
Participant flow
Recruitment details
Between April 2018 and October 2019, 52 outpatient pulmonary clinic patients were approached about potential participation in the study. Twenty-six participants signed a written informed consent prior to enrollment and the HIPAA-compliant study protocol was approved by the Institutional Review Board of Duke University Medical Center (Pro00086693). Six participants were either withdrawn by the PI or voluntarily withdrew prior to starting the study.
Pre-assignment details
All subjects who were on regular inhalation therapies for COPD underwent a wash-out period of 7-14 days, during which time they stopped all inhaled corticosteroids, long-acting beta agonist (LABA), and long-acting muscarinic receptor antagonist (LAMA). The subjects were allowed to use inhaled albuterol as needed.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Twenty subjects completed the study. One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit; thus, a total of 17 subjects (8M 9F) were included in the data analysis. Subjects were treated with Bevespi 2 puffs twice a day for 2 weeks. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 5 |
| Race/Ethnicity, Customized African-American | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 17 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants |
| Race/Ethnicity, Customized Non-Hispanic | 17 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 17 |
| other Total, other adverse events | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 |
Outcome results
Primary
Barrier Uptake.
Diffusion of Xe gas across the lung membrane into the blood. This measures how well oxygen goes through the lung into the blood.
Time frame: 2 weeks
Population: 17 patients with GOLD 2 or 3 COPD 17 participants were included in the data analysis. One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment | Barrier Uptake. | increase in barrier uptake | 13 Participants |
| Treatment | Barrier Uptake. | No increase in barrier uptake | 4 Participants |
Primary
Red Blood Cell (RBC) Uptake
Amount of Xe gas that enters the blood stream after it diffuses across the lung membrane
Time frame: 2 weeks
Population: GOLD 2 and 3 COPD 17 participants were included in the data analysis. One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment | Red Blood Cell (RBC) Uptake | Decrease in red blood cell (RBC) uptake | 10 Participants |
| Treatment | Red Blood Cell (RBC) Uptake | No decrease in red blood cell (RBC) uptake | 7 Participants |
Primary
Ventilation Distribution as Measured by Ventilation Defect+Low Percent
The ventilation distribution as measured by ventilation defect+low percent is to measure the area of the lung that has no air.
Time frame: Week 2
Population: 17 participants were included in the data analysis. One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Ventilation Distribution as Measured by Ventilation Defect+Low Percent | Baseline | 57.8 percentage of total ventilation | Standard Deviation 8.4 |
| Treatment | Ventilation Distribution as Measured by Ventilation Defect+Low Percent | Week 2 | 52.5 percentage of total ventilation | Standard Deviation 10.6 |
p-value: 0.006Paired t-test
Secondary
6-minute Walk Test (6MWT)
The 6-minute walk test (6MWT) measures the distance walked at a natural pace for 6 minutes.
Time frame: 2 weeks
Population: One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | 6-minute Walk Test (6MWT) | 16.2 meters | Standard Deviation 37.6 |
Secondary
COPD Assessment Test (CAT) Score
Functional measurement for COPD patients. Range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD on a patient's life.
Time frame: 2 weeks
Population: One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | COPD Assessment Test (CAT) Score | -3.8 score on a scale | Standard Deviation 4.5 |
Secondary
Pulmonary Function Test - Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
DLCO measures the ability of oxygen to travel from the air sacs of the lungs to the blood stream.
Time frame: 2 weeks
Population: One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Pulmonary Function Test - Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) | 0.2 mL/min/mmHg | Standard Deviation 1.3 |
Secondary
Pulmonary Function Test - Forced Expiratory Volume-one Second (FEV1)
FEV1 is a lung airflow measure to assess the amount of air that can be blown out in one second.
Time frame: 2 weeks
Population: One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Pulmonary Function Test - Forced Expiratory Volume-one Second (FEV1) | 219 ml | Standard Deviation 168 |
Secondary
Pulmonary Function Test - Forced Vital Capacity (FVC)
Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible, as measured by spirometry.
Time frame: 2 weeks
Population: One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit.~17 participants were included in the data analysis. One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Pulmonary Function Test - Forced Vital Capacity (FVC) | 342 ml | Standard Deviation 286 |
Secondary
Pulmonary Function Test - Residual Volume (RV)
Residual volume (RV) is the volume of air remaining in the lungs after a maximal exhalation.
Time frame: 2 weeks
Population: One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Pulmonary Function Test - Residual Volume (RV) | -108 ml | Standard Deviation 508 |
Secondary
Pulmonary Function Test - Total Lung Capacity (TLC)
Total Lung Capacity (TLC) is the volume in the lungs at a maximal inhalation.
Time frame: 2 weeks
Population: One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Pulmonary Function Test - Total Lung Capacity (TLC) | 183 ml | Standard Deviation 411 |
Secondary
Rating of Perceived Dyspnea (RPD) Scale
A patient reported outcome to measure perceived exertion during physical activity. The RPD scale goes from 0 to 10, where 0 = no shortness of breath at all and 10 = maximal shortness of breath (needing to stop the exercise or activity).
Time frame: 2 weeks
Population: One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Rating of Perceived Dyspnea (RPD) Scale | -0.75 score on a scale | Standard Deviation 2.33 |
Secondary
St. George's Respiratory Questionnaire (SGRQ) Score
The SGRQ is used to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.
Time frame: 2 weeks
Population: One subject was excluded from data analysis due to poor image signal-to-noise ratio (SNR), and two elected not to return for a post-treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | St. George's Respiratory Questionnaire (SGRQ) Score | -1.2 score on a scale | Standard Deviation 5.8 |