Trial Outcomes & Findings for Response to Diaphragmatic Pacing in Subjects With Pompe Disease (NCT NCT02354651)

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

9 participants

Primary outcome timeframe

Baseline, Day 180

Results posted on

2023-08-01

Participant Flow

Subjects were eligible to receive a diaphragmatic pacemaker as part of their clinical care. Some subjects who enrolled decided not to include pacing as part of their clinical care (n=2), or were found to have medical conditions that made them ineligible (n=1).

Participant milestones

Participant milestones
Measure	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. Diaphragm conditioning via phrenic nerve stimulation: Diaphragm conditioning will be prescribed by the patient's clinical team.
Overall Study STARTED	9
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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. Diaphragm conditioning via phrenic nerve stimulation: Diaphragm conditioning will be prescribed by the patient's clinical team.
Overall Study Withdrawal by Subject	2
Overall Study Physician Decision	1

Baseline Characteristics

Response to Diaphragmatic Pacing in Subjects With Pompe Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pompe Subjects Receiving NeuDx DPS n=6 Participants Patients will receive resting breathing pattern evaluation, phrenic nerve stimulation, maximal inspiratory pressure (MIP) testing, forced expiratory testing, and EMG. Diaphragm conditioning via phrenic nerve stimulation: Diaphragm pacing will be prescribed by the patient's clinical team.
Age, Categorical <=18 years	3 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	24.5 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Ventilator-Free Breathing	0.52 hours of unassisted ventilation per day n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day 180

Population: Full sample

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.

Outcome measures

Outcome measures
Measure	Pompe Subjects Receiving NeuRx DPS n=6 Participants Patients will receive resting breathing pattern evaluation, phrenic nerve stimulation, maximal inspiratory pressure (MIP) testing, forced expiratory testing, and EMG. Diaphragm conditioning via phrenic nerve stimulation: Diaphragm pacing will be prescribed by the patient's clinical team.
Off-ventilator Spontaneous Breathing (SB) at Baseline and Day 180 Baseline	0.52 hours per day Interval 0.0 to 1.5
Off-ventilator Spontaneous Breathing (SB) at Baseline and Day 180 Day 180	4.72 hours per day Interval 0.04 to 12.0

SECONDARY outcome

Timeframe: Baseline, Day 180

Population: Subjects 4 and 6 were unavailable for MIP testing at baseline; Subjects 1 and 3 were unavailable for MIP testing at 6 months.

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.

Outcome measures

Outcome measures
Measure	Pompe Subjects Receiving NeuRx DPS n=4 Participants Patients will receive resting breathing pattern evaluation, phrenic nerve stimulation, maximal inspiratory pressure (MIP) testing, forced expiratory testing, and EMG. Diaphragm conditioning via phrenic nerve stimulation: Diaphragm pacing will be prescribed by the patient's clinical team.
Maximal Inspiratory Pressure (MIP) at Baseline and Day 180 Baseline	35.6 cm H2O Interval 12.8 to 65.0
Maximal Inspiratory Pressure (MIP) at Baseline and Day 180 180 Days	32.7 cm H2O Interval 8.3 to 61.0

SECONDARY outcome

Timeframe: Day 180

Population: Minute ventilation during off-ventilator breathing was assessed with and without diaphragm pacing at approximately 6 months post-implant.

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.

Outcome measures

Outcome measures
Measure	Pompe Subjects Receiving NeuRx DPS n=4 Participants Patients will receive resting breathing pattern evaluation, phrenic nerve stimulation, maximal inspiratory pressure (MIP) testing, forced expiratory testing, and EMG. Diaphragm conditioning via phrenic nerve stimulation: Diaphragm pacing will be prescribed by the patient's clinical team.
Change in Resting Breathing Pattern Without diaphragm pacer	5.05 L/min Standard Deviation 1.73
Change in Resting Breathing Pattern With diaphragm pacer	5.41 L/min Standard Deviation 3.54

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pompe Subjects Receiving NeuRx DPS n=4 Participants Patients will receive resting breathing pattern evaluation, phrenic nerve stimulation, maximal inspiratory pressure (MIP) testing, forced expiratory testing, and EMG. Diaphragm conditioning via phrenic nerve stimulation: Diaphragm pacing will be prescribed by the patient's clinical team.
Diaphragm Electromyogram (EMG) at Day 180	57.3 RMS diaphragm (% of MIP) Standard Deviation 38.9

OTHER_PRE_SPECIFIED outcome

Timeframe: 180 days

Population: Patients with Pompe disease who received diaphragm pacing

Number of hours used per day diaphragm pacing occurred by subjects

Outcome measures

Outcome measures
Measure	Pompe Subjects Receiving NeuRx DPS n=6 Participants Patients will receive resting breathing pattern evaluation, phrenic nerve stimulation, maximal inspiratory pressure (MIP) testing, forced expiratory testing, and EMG. Diaphragm conditioning via phrenic nerve stimulation: Diaphragm pacing will be prescribed by the patient's clinical team.
Hours Per Day of Diaphragm Pacing	20.3 hours per day of diaphragm pacing Interval 2.0 to 24.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 180 Days

Population: Magnetic stimulation was used as assessment for determining clinical eligibility for diaphragm pacing. It was not available at follow-up observational visits.

EMG response to supramaximal bilateral stimulation of the phrenic nerves.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 180 days

Population: The Severe Respiratory Insufficiency Questionnaire was validated only in adults. Adults who participated did not complete the questionnaire at Day 180.

Patient reported measure of impact of respiratory insufficiency on functional mobility

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 180 days

Population: Only 2 patients were able to complete voluntary cough during a 180-day visit

Peak expiratory flow obtained during voluntary cough

Outcome measures

Outcome measures
Measure	Pompe Subjects Receiving NeuRx DPS n=2 Participants Patients will receive resting breathing pattern evaluation, phrenic nerve stimulation, maximal inspiratory pressure (MIP) testing, forced expiratory testing, and EMG. Diaphragm conditioning via phrenic nerve stimulation: Diaphragm pacing will be prescribed by the patient's clinical team.
Forced Expiratory Flow	42.65 L/min Interval 36.4 to 48.9

Adverse Events

Pompe Subjects Receiving NeuRx DPS

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pompe Subjects Receiving NeuRx DPS n=6 participants at risk Patients will receive resting breathing pattern evaluation, phrenic nerve stimulation, maximal inspiratory pressure (MIP) testing, forced expiratory testing, and EMG. Diaphragm conditioning via phrenic nerve stimulation: Diaphragm pacing will be prescribed by the patient's clinical team.
Respiratory, thoracic and mediastinal disorders Pneumonia	33.3% 2/6 • Number of events 2 • Longitudinal observational data through January 2019. Post-operative observation time frame ranged from 89 months in subject 1, to 45 months in subject 6..
Nervous system disorders Seizures	16.7% 1/6 • Number of events 2 • Longitudinal observational data through January 2019. Post-operative observation time frame ranged from 89 months in subject 1, to 45 months in subject 6..
Musculoskeletal and connective tissue disorders Scoliosis requiring spinal fusion	16.7% 1/6 • Number of events 1 • Longitudinal observational data through January 2019. Post-operative observation time frame ranged from 89 months in subject 1, to 45 months in subject 6..

Other adverse events

Other adverse events
Measure	Pompe Subjects Receiving NeuRx DPS n=6 participants at risk Patients will receive resting breathing pattern evaluation, phrenic nerve stimulation, maximal inspiratory pressure (MIP) testing, forced expiratory testing, and EMG. Diaphragm conditioning via phrenic nerve stimulation: Diaphragm pacing will be prescribed by the patient's clinical team.
Skin and subcutaneous tissue disorders Skin irritation	50.0% 3/6 • Number of events 3 • Longitudinal observational data through January 2019. Post-operative observation time frame ranged from 89 months in subject 1, to 45 months in subject 6..
Hepatobiliary disorders Cholecystitis	16.7% 1/6 • Number of events 1 • Longitudinal observational data through January 2019. Post-operative observation time frame ranged from 89 months in subject 1, to 45 months in subject 6..
Respiratory, thoracic and mediastinal disorders Respiratory infection	33.3% 2/6 • Number of events 2 • Longitudinal observational data through January 2019. Post-operative observation time frame ranged from 89 months in subject 1, to 45 months in subject 6..
Gastrointestinal disorders Diarrhea	16.7% 1/6 • Number of events 1 • Longitudinal observational data through January 2019. Post-operative observation time frame ranged from 89 months in subject 1, to 45 months in subject 6..
Skin and subcutaneous tissue disorders Occipital pressure ulcer	16.7% 1/6 • Number of events 1 • Longitudinal observational data through January 2019. Post-operative observation time frame ranged from 89 months in subject 1, to 45 months in subject 6..
Product Issues Damaged infusion port	16.7% 1/6 • Number of events 1 • Longitudinal observational data through January 2019. Post-operative observation time frame ranged from 89 months in subject 1, to 45 months in subject 6..
Respiratory, thoracic and mediastinal disorders Sinusitis	16.7% 1/6 • Number of events 1 • Longitudinal observational data through January 2019. Post-operative observation time frame ranged from 89 months in subject 1, to 45 months in subject 6..
Product Issues Breakage of pacemaker external wires	83.3% 5/6 • Number of events 9 • Longitudinal observational data through January 2019. Post-operative observation time frame ranged from 89 months in subject 1, to 45 months in subject 6..

Additional Information

Dr. Barbara Smith

University of Florida

Phone: 3522945315

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place