Dynamic Respiratory Muscle Function in Late-Onset Pompe Disease

NCT02354664 | Completed Results

• 1 other identifier: IRB201400763
• Study Type: observational
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Pompe Disease

Keywords

respiratory test; respiratory muscle endurance; spirometry

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• Thoracic MRI

  Day 1

Study Arms (2)

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; Other: Spirometry; Other: Inspiratory Load Compensation; Other: Maximal Inspiratory Pressure; Other: Resting Breathing Pattern; Other: Respiratory Muscle Endurance Test

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; Other: Spirometry; Other: Inspiratory Load Compensation; Other: Maximal Inspiratory Pressure; Other: Resting Breathing Pattern; Other: Respiratory Muscle Endurance Test

Interventions

Thoracic MRI OTHER

Imaging of the diaphragm will be completed during resting breathing, and then during a maximal voluntary ventilation maneuver.

Control subjects; Pompe subjects

Spirometry OTHER

Upright forced vital capacity (FVC)

Control subjects; Pompe subjects

Inspiratory Load Compensation OTHER

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.

Control subjects; Pompe subjects

Maximal Inspiratory Pressure OTHER

Measure the maximal airflow on inhalation

Also known as: MIP

Control subjects; Pompe subjects

Resting Breathing Pattern OTHER

The breathing pattern will be assessed when the subject is seated and in a relaxed state.

Control subjects; Pompe subjects

Respiratory Muscle Endurance Test OTHER

Evaluates the time limit that a participant can maintain ventilation while breathing with a submaximal inspiratory threshold load.

Control subjects; Pompe subjects

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• Confirmed diagnosis of Pompe disease OR
• Be an age and gender-matched unaffected control subject

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Florida: lead
• BioMarin Pharmaceutical: collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32606, United States

Location

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Barbara Smith, Assistant Professor
• Organization: University of Florida

bksmith@phhp.ufl.edu

352-294-5315

Study Officials

• Barbara K. Smith, PT, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2015
• First Posted: February 3, 2015
• Study Start: April 1, 2015
• Primary Completion: October 19, 2016
• Study Completion: October 19, 2016
• Last Updated: June 24, 2024
• Results First Posted: June 24, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)