Dynamic Respiratory Muscle Function in Late-Onset Pompe Disease (DRMF)

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.

Study Overview

• Status: Completed
• Conditions: Pompe Disease
• Intervention / Treatment: Other: Thoracic MRI; Other: Spirometry; Other: Inspiratory Load Compensation; Other: Maximal Inspiratory Pressure; Other: Resting Breathing Pattern; Other: Respiratory Muscle Endurance Test

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).

• Study Type: Observational
• Enrollment (Actual): 14

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32606
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Subjects with late-onset Pompe disease, age 20-65 years, and age and gender-matched unaffected control subjects

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pompe subjects; These subjects will receive a thoracic MRI, spirometry, inspiratory load compensation, maximal inspiratory pressure, resting breathing pattern, respiratory muscle endurance test.	Other: Thoracic MRI; Imaging of the diaphragm will be completed during resting breathing, and then during a maximal voluntary ventilation maneuver.; Other: Spirometry; Upright forced vital capacity (FVC); Other: Inspiratory 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.; Other: Maximal Inspiratory Pressure; Measure the maximal airflow on inhalation; Other Names: MIP; Other: Resting Breathing Pattern; The breathing pattern will be assessed when the subject is seated and in a relaxed state.; Other: Respiratory Muscle Endurance Test; Evaluates the time limit that a participant can maintain ventilation while breathing with a submaximal inspiratory threshold load.
Control subjects; These subjects will receive a thoracic MRI, spirometry, inspiratory load compensation, maximal inspiratory pressure, resting breathing pattern, respiratory muscle endurance test.	Other: Thoracic MRI; Imaging of the diaphragm will be completed during resting breathing, and then during a maximal voluntary ventilation maneuver.; Other: Spirometry; Upright forced vital capacity (FVC); Other: Inspiratory 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.; Other: Maximal Inspiratory Pressure; Measure the maximal airflow on inhalation; Other Names: MIP; Other: Resting Breathing Pattern; The breathing pattern will be assessed when the subject is seated and in a relaxed state.; Other: Respiratory Muscle Endurance Test; Evaluates the time limit that a participant can maintain ventilation while breathing with a submaximal inspiratory threshold load.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1
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.	Day 2
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.	Day 1
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.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: BioMarin Pharmaceutical
• Investigators: Principal Investigator: Barbara K. Smith, PT, PhD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): October 19, 2016
• Study Completion (Actual): October 19, 2016

Study Registration Dates

• First Submitted: January 21, 2015
• First Submitted That Met QC Criteria: January 29, 2015
• First Posted (Estimated): February 3, 2015

Study Record Updates

• Last Update Posted (Actual): June 24, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: spirometry; respiratory muscle endurance; respiratory test
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease; Glycogen Storage Disease Type II
• Other Study ID Numbers: IRB201400763

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No