Pompe Disease
Conditions
Keywords
respiratory test, respiratory muscle endurance, spirometry
Brief summary
This study intends to evaluate dynamic respiratory motor performance as a valuable measure of pulmonary function in adults with late-onset Pompe disease. The investigators will adopt a strategy that includes comprehensive evaluations of respiratory volume, flow, and timing parameters during resting and loaded breathing. These evaluations will then be associated to the standard clinical measure of maximal inspiratory pressure, the static inspiratory muscle function, as well as magnetic resonance imaging of thoracic expansion and diaphragmatic descent at rest and with exertion. Outcomes in participants with late-onset Pompe disease will be contrasted to the function of age- and gender-matched control subjects. This approach will enable the investigators to evaluate the relationship between dynamic diaphragmatic function and respiratory motor function.
Detailed description
The following tests will be completed over a two-day period: Respiratory pressure tests, breathing test, magnetic resonance imaging and magnetic resonance spectroscopy (MRI and MRS).
Interventions
OTHERThoracic MRI
Imaging of the diaphragm will be completed during resting breathing, and then during a maximal voluntary ventilation maneuver.
OTHERSpirometry
Upright forced vital capacity (FVC)
OTHERInspiratory Load Compensation
A spring-loaded pressure device will resist inspiration. The patient must generate the threshold inspiratory pressure to receive airflow. The changes in breathing timing, flow and volume will be recorded.
Measure the maximal airflow on inhalation
OTHERResting Breathing Pattern
The breathing pattern will be assessed when the subject is seated and in a relaxed state.
OTHERRespiratory Muscle Endurance Test
Evaluates the time limit that a participant can maintain ventilation while breathing with a submaximal inspiratory threshold load.
Sponsors
BioMarin Pharmaceutical
University of Florida
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Confirmed diagnosis of Pompe disease OR * Be an age and gender-matched unaffected control subject
Exclusion criteria
* Pre-existing obstructive lung disease or asthma * Forced vital capacity (FVC) \<30% or \>80% of age/gender predicted values * Inability to travel to the study site * Requirement for positive pressure ventilator support when awake and upright * Participation in longitudinal studies that may independently alter lung function * Presence of any other chronic medical condition that, in the opinion of the investigator, would make the subject unsuitable for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inspiratory Load Compensation - Inspiratory Volume | Day 1 | For ILC testing, a commercially available, spring-loaded device provided a pressure load to inspiration that is independent of inspiratory flow. The patient had to generate enough threshold inspiratory pressure in order to receive airflow. The tension of the spring was adjusted to regulate the threshold pressure of the imposed load. Volume, flow and timing responses were evaluated to an inspiratory threshold load equivalent to 40% of PImax. |
| Respiratory Muscle Endurance Task | Day 2 | Endurance was evaluated by identifying the time limit (Tlim) that a participant could maintain ventilation while breathing with a submaximal inspiratory threshold load. The test begin after a one-hour rest. After reaching a steady state breathing pattern (e.g. stable tidal volumes for \>30 seconds), a threshold inspiratory load equivalent to 40% of PIMAX was placed on the inspiratory port of the mouthpiece. During the loaded breathing condition, the respiratory rate was set to each subject's self-selected resting breathing rate. The perceived exertion was monitored, and subjects received encouragement to maintain the target rate and mouth pressure. Encouragement was provided to maintain the established breathing pattern and to continue to task failure. The test ended when the subject could not open the threshold valve for three consecutive breaths. |
| Inspiratory Load Compensation - Inspiratory Flow | Day 1 | For ILC testing, a commercially available, spring-loaded device provided a pressure load to inspiration that is independent of inspiratory flow. The patient had to generate enough threshold inspiratory pressure in order to receive airflow. The tension of the spring was adjusted to regulate the threshold pressure of the imposed load. Volume, flow and timing responses were evaluated to an inspiratory threshold load equivalent to 40% of PImax. |
| Inspiratory Load Compensation - Inspiratory Time | Day 1 | For ILC testing, a commercially available, spring-loaded device provided a pressure load to inspiration that is independent of inspiratory flow. The patient had to generate enough threshold inspiratory pressure in order to receive airflow. The tension of the spring was adjusted to regulate the threshold pressure of the imposed load. Volume, flow and timing responses were evaluated to an inspiratory threshold load equivalent to 40% of PImax. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Thoracic MRI | Day 1 | Chest wall and diaphragmatic motions was measured in three planes with dynamic magnetic resonance imaging (MRI). The cradio-caudal change in diaphragm excursion between full inspiration and full expiration (representing diaphragm descent) was measured in the frontal plane. The anterior-posterior change in the area of the right and left sides of the chest cavity was measured in the sagittal plane (representing chest expansion). Diaphragm and chest excursion was recorded dynamically during 30-second periods of resting breathing and deep breathing. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pompe Subjects Participants were between the ages of 20-65 years with a confirmed diagnosis of Pompe disease. | 7 |
| Control Subjects Participants were between the ages of 20-65 years and were healthy adults. | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Pompe Subjects | Control Subjects | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 7 Participants | 14 Participants |
| Age, Continuous | 43.6 years STANDARD_DEVIATION 12.8 | 42.6 years STANDARD_DEVIATION 15.7 | 43.1 years STANDARD_DEVIATION 13.7 |
| Forced vital capacity | 59 % predicted STANDARD_DEVIATION 22 | 110 % predicted STANDARD_DEVIATION 45 | 84 % predicted STANDARD_DEVIATION 34 |
| Maximal Inspiratory Pressure | 59 cm H2O STANDARD_DEVIATION 20 | 95 cm H2O STANDARD_DEVIATION 111 | 77 cm H2O STANDARD_DEVIATION 32 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 7 | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
Inspiratory Load Compensation - Inspiratory Flow
For ILC testing, a commercially available, spring-loaded device provided a pressure load to inspiration that is independent of inspiratory flow. The patient had to generate enough threshold inspiratory pressure in order to receive airflow. The tension of the spring was adjusted to regulate the threshold pressure of the imposed load. Volume, flow and timing responses were evaluated to an inspiratory threshold load equivalent to 40% of PImax.
Time frame: Day 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pompe Subjects | Inspiratory Load Compensation - Inspiratory Flow | Inspiratory Flow - Loaded | 18.57 L/min | Standard Deviation 12.52 |
| Pompe Subjects | Inspiratory Load Compensation - Inspiratory Flow | Inspiratory Flow - Unloaded | 47.05 L/min | Standard Deviation 6.4 |
| Control Subjects | Inspiratory Load Compensation - Inspiratory Flow | Inspiratory Flow - Loaded | 21.62 L/min | Standard Deviation 20.09 |
| Control Subjects | Inspiratory Load Compensation - Inspiratory Flow | Inspiratory Flow - Unloaded | 42.50 L/min | Standard Deviation 8.82 |
Primary
Inspiratory Load Compensation - Inspiratory Time
For ILC testing, a commercially available, spring-loaded device provided a pressure load to inspiration that is independent of inspiratory flow. The patient had to generate enough threshold inspiratory pressure in order to receive airflow. The tension of the spring was adjusted to regulate the threshold pressure of the imposed load. Volume, flow and timing responses were evaluated to an inspiratory threshold load equivalent to 40% of PImax.
Time frame: Day 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pompe Subjects | Inspiratory Load Compensation - Inspiratory Time | Inspiratory Time - Loaded | 1.76 seconds | Standard Deviation 0.55 |
| Pompe Subjects | Inspiratory Load Compensation - Inspiratory Time | Inspiratory Time - Unloaded | 1.41 seconds | Standard Deviation 0.27 |
| Control Subjects | Inspiratory Load Compensation - Inspiratory Time | Inspiratory Time - Loaded | 3.80 seconds | Standard Deviation 3.91 |
| Control Subjects | Inspiratory Load Compensation - Inspiratory Time | Inspiratory Time - Unloaded | 1.93 seconds | Standard Deviation 0.79 |
Primary
Inspiratory Load Compensation - Inspiratory Volume
For ILC testing, a commercially available, spring-loaded device provided a pressure load to inspiration that is independent of inspiratory flow. The patient had to generate enough threshold inspiratory pressure in order to receive airflow. The tension of the spring was adjusted to regulate the threshold pressure of the imposed load. Volume, flow and timing responses were evaluated to an inspiratory threshold load equivalent to 40% of PImax.
Time frame: Day 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pompe Subjects | Inspiratory Load Compensation - Inspiratory Volume | Inspiratory Volume - Loaded | 288.41 mL | Standard Deviation 136.77 |
| Pompe Subjects | Inspiratory Load Compensation - Inspiratory Volume | Inspiratory Volume - Unloaded | 743.71 mL | Standard Deviation 145.42 |
| Control Subjects | Inspiratory Load Compensation - Inspiratory Volume | Inspiratory Volume - Loaded | 554.34 mL | Standard Deviation 550.26 |
| Control Subjects | Inspiratory Load Compensation - Inspiratory Volume | Inspiratory Volume - Unloaded | 927.57 mL | Standard Deviation 352.09 |
Primary
Respiratory Muscle Endurance Task
Endurance was evaluated by identifying the time limit (Tlim) that a participant could maintain ventilation while breathing with a submaximal inspiratory threshold load. The test begin after a one-hour rest. After reaching a steady state breathing pattern (e.g. stable tidal volumes for \>30 seconds), a threshold inspiratory load equivalent to 40% of PIMAX was placed on the inspiratory port of the mouthpiece. During the loaded breathing condition, the respiratory rate was set to each subject's self-selected resting breathing rate. The perceived exertion was monitored, and subjects received encouragement to maintain the target rate and mouth pressure. Encouragement was provided to maintain the established breathing pattern and to continue to task failure. The test ended when the subject could not open the threshold valve for three consecutive breaths.
Time frame: Day 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pompe Subjects | Respiratory Muscle Endurance Task | 2.9 minutes | Standard Deviation 2.8 |
| Control Subjects | Respiratory Muscle Endurance Task | 7.7 minutes | Standard Deviation 3.1 |
Secondary
Thoracic MRI
Chest wall and diaphragmatic motions was measured in three planes with dynamic magnetic resonance imaging (MRI). The cradio-caudal change in diaphragm excursion between full inspiration and full expiration (representing diaphragm descent) was measured in the frontal plane. The anterior-posterior change in the area of the right and left sides of the chest cavity was measured in the sagittal plane (representing chest expansion). Diaphragm and chest excursion was recorded dynamically during 30-second periods of resting breathing and deep breathing.
Time frame: Day 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pompe Subjects | Thoracic MRI | Tidal Breathing - Cranio-Caudal Excursion | 0.85 cm | Standard Deviation 0.76 |
| Pompe Subjects | Thoracic MRI | Tidal Breathing - Anterior-Posterior Excursion | 0.54 cm | Standard Deviation 0.47 |
| Pompe Subjects | Thoracic MRI | Inspiratory Capacity - Cranio-Caudal Excursion | 1.93 cm | Standard Deviation 2.38 |
| Pompe Subjects | Thoracic MRI | Inspiratory Capacity - Anterior-Posterior Excursion | 1.55 cm | Standard Deviation 1.11 |
| Control Subjects | Thoracic MRI | Inspiratory Capacity - Anterior-Posterior Excursion | 1.79 cm | Standard Deviation 1.94 |
| Control Subjects | Thoracic MRI | Tidal Breathing - Cranio-Caudal Excursion | 1.88 cm | Standard Deviation 0.71 |
| Control Subjects | Thoracic MRI | Inspiratory Capacity - Cranio-Caudal Excursion | 5.77 cm | Standard Deviation 1.2 |
| Control Subjects | Thoracic MRI | Tidal Breathing - Anterior-Posterior Excursion | 0.58 cm | Standard Deviation 0.8 |