Response to Diaphragmatic Pacing in Subjects With Pompe Disease

Completed

Brief Summary: 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).

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)

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Patients With Pompe Disease Eligible for Diaphragm Pacing	Diaphragm conditioning via phrenic nerve stimulation	Patients will receive tests of breathing pattern, phrenic nerve stimulation, maximal inspiratory pressure (MIP), forced expiration, and EMG.

Primary Outcome Measures

Name	Time	Method
Off-ventilator Spontaneous Breathing (SB) at Baseline and Day 180	Baseline, 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.

Secondary Outcome Measures

Name	Time	Method
Maximal Inspiratory Pressure (MIP) at Baseline and Day 180	Baseline, 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.
Diaphragm Electromyogram (EMG) at Day 180	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.
Change in Resting Breathing Pattern	Day 180	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.