Response to Diaphragmatic Pacing in Subjects With Pompe Disease

The purpose of this study is to determine the effect of diaphragm pacing on respiratory function in subjects with Pompe disease by evaluating the duration and pattern of spontaneous respiratory function versus paced ventilation respiratory function in patients with Pompe disease who have received the NeuDx Diaphragm pacer (DPS).

Study Overview

• Status: Completed
• Conditions: Pompe Disease
• Intervention / Treatment: Other: Diaphragm conditioning via phrenic nerve stimulation

Detailed Description

Subjects with Pompe disease who are scheduled to receive a NeuRx Diaphragm pacer (DPS) will be invited to participate in this study. The following tests will be performed during participation in the study:

1. Forced expiratory tests
2. Maximal Inspiratory Pressure (MIP)
3. Resting Breathing Pattern
4. Phrenic Nerve Function Evaluation with EMG
5. Severe Respiratory Insufficiency Questionnaire
6. Magnetic stimulation

7. Diaphragm conditioning consisting of:

   1. The external stimulator settings
   2. The duration of diaphragm stimulation
   3. Off-ventilator spontaneous breathing (SB)

• Study Type: Observational
• Enrollment (Actual): 9

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects with Pompe disease who are eligible for NeuRx DPS implantation

Description

Inclusion Criteria:

• Diagnosis of Pompe disease as defined by mutational analysis, GAA enzyme activity assay in blood spot, and/or fibroblast culture less than 40% of control value
• Medically and functionally eligible for NeuRx DPS implantation, as determined by a clinical surgical evaluation. The surgeon will determine eligibility through pulmonary function tests, ability to stimulate your diaphragm, and arterial blood gas levels. Eligibility may also be determined by your response to traditional respiratory strengthening exercises without a pacemaker.
• History of mechanical ventilation dependence (six or more hours of invasive or non-invasive mechanical ventilation support daily for at least 21 days in duration

Exclusion Criteria:

• Current participation in another treatment study (other than enzyme replacement therapy) directed at improving diaphragm function
• Unable to complete pulmonary function testing

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients With Pompe Disease Eligible for Diaphragm Pacing; Patients will receive tests of breathing pattern, phrenic nerve stimulation, maximal inspiratory pressure (MIP), forced expiration, and EMG.	Other: Diaphragm conditioning via phrenic nerve stimulation; Diaphragm pacing will be prescribed by the patient's clinical team.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Off-ventilator Spontaneous Breathing (SB) at Baseline and Day 180	The patient will undergo an initial trial of unassisted breathing with the diaphragm pacer turned on. The duration of SB with pacing will be increased to tolerance, using a protocol. If the patient cannot initially complete at least 30-minute bouts of paced SB, then the focus of breathing trials will be to breathe with reduced support from the mechanical ventilator. These measures were generated utilizing ventilator chip data for SB that has been averaged.	Baseline, Day 180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal Inspiratory Pressure (MIP) at Baseline and Day 180	MIP will be measured with a manometer connected to the airway opening of the subject, which occludes the airway and prevents airflow. A nose clip will be used to prevent leakage and the subject is instructed to suck air from the tube with as much force as possible. Measurements will be obtained with the subject sitting upright. Transdiaphragmatic pressure (Pdi) may be calculated with esophageal and gastric manometry during MIP. The measurement will be taken three times and the best value will be reported.	Baseline, Day 180
Change in Resting Breathing Pattern	Resting ventilatory flow and timing will be recorded with a pneumotachograph and pressure transducer connected to the airway opening, to calculate minute ventilation. If a patient routinely uses MV throughout the day, the sensing equipment can be placed in series to the breathing tubes. Breathing pattern will be measured for a minimum of ten minutes.	Day 180
Diaphragm Electromyogram (EMG) at Day 180	This activity reflects the activity of the diaphragm and phrenic nerve. The wires that are implanted for diaphragm pacemaker will be connected to a computer and recording equipment to monitor the activity of the diaphragm muscle during breathing at the lowest level of ventilator assistance. This EMG data is measured in units of microvolts per second and expressed as a percentage of the level of diaphragm EMG activity recorded during MIP maneuvers.	Day 180

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hours Per Day of Diaphragm Pacing	Number of hours used per day diaphragm pacing occurred by subjects	180 days
Magnetic Stimulation	EMG response to supramaximal bilateral stimulation of the phrenic nerves.	180 Days
Severe Respiratory Insufficiency Questionnaire	Patient reported measure of impact of respiratory insufficiency on functional mobility	180 days
Forced Expiratory Flow	Peak expiratory flow obtained during voluntary cough	180 days

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Barbara K Smith, PT, PhD, University of Florida

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): January 1, 2023

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): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: mechanical ventilation; diaphragm pacing; Pompe disease
• 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: IRB201600161-N; 003-2013 (Other Identifier: University of Florida pre-conversion); 1R21HD090752-01 (U.S. NIH Grant/Contract)