ClinicalTrials.gov
ClinicalTrials.gov Menu

Response to Diaphragmatic Pacing in Subjects With Pompe Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02354651
Recruitment Status : Recruiting
First Posted : February 3, 2015
Last Update Posted : April 27, 2018
Sponsor:
Collaborators:
Acid Maltase Deficiency Association
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
University of Florida

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).

Condition or disease Intervention/treatment
Pompe Disease Other: Pulmonary function testing Other: Resting breathing pattern Other: Respiratory muscle endurance test Other: Phrenic nerve stimulation Other: Maximal inspiratory pressure Other: Forced expiratory testing Other: EMG

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
Estimated Enrollment : 12 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Response to Diaphragmatic Pacing in Subjects With Pompe Disease
Study Start Date : May 2013
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2019


Group/Cohort Intervention/treatment
Pompe subjects receiving NeuDx DPS
Patients will receive pulmonary function testing, resting breathing pattern evaluation, respiratory muscle endurance testing, phrenic nerve stimulation, maximal inspiratory pressure (MIP) testing, forced expiratory testing, and EMG.
Other: Pulmonary function testing
Measure the breathing muscles ability to move gases in and out

Other: Resting breathing pattern
Record resting ventilatory flow and timing

Other: Respiratory muscle endurance test
Subjects will maintain breathing rate with loaded breaths

Other: Phrenic nerve stimulation
Other: Maximal inspiratory pressure
Measure the maximal airflow on inhalation
Other Name: MIP

Other: Forced expiratory testing
Measure the maximal airflow and volume of gas that can be exhaled with the subject breathing or coughing forcefully

Other: EMG
Evaluate electrical activity of diaphragm via pacer




Primary Outcome Measures :
  1. Change in off-ventilator spontaneous breathing (SB) at Baseline, Day 3, 14, and 180 [ Time Frame: Change from Baseline to Day 3, 14, and 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.


Secondary Outcome Measures :
  1. Change in Pulmonary Function Test at Day 3, 14, and 180 [ Time Frame: Change from Day 3, 14, and 180 ]
    Pulmonary function testing is used routinely in clinical medicine and has no inherent complications. Subjects who may not be able to complete conventional PFTs may undergo impulse oscillometry for assessment of lung function.

  2. Change in Forced expiratory tests at Screening, Baseline, Day 14, and 180 [ Time Frame: Change from Screening, Baseline, Day 14, and Day 180 ]
    Forced expiratory tests measure the maximal airflow and volume of gas that can be exhaled with the subject breathing or coughing forcefully. A nose clip, or cuffed tracheostomy with cuff inflated is used to prevent leakage. The subject deeply inhales and then exhales as forcefully and deeply as possible. Measurements will be obtained with the subject sitting upright and then repeated with the subject in the supine position, if tolerated. A minimum of three trials will be obtained in each position with <5% variability [13]. The highest value obtained in each position will be reported.

  3. Change in Maximal Inspiratory Pressure (MIP) at Screening, Baseline, Day 14, and 180 [ Time Frame: Change from Screening, Baseline, Day 14, 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.

  4. Change in Resting Breathing Pattern at Screening, Baseline, Day 3, Day 14, and Day 180 [ Time Frame: Change from Screening, Baseline, Day 3, Day 14, and Day 180 ]
    Resting ventilatory flow and timing will be recorded with a pneumotachograph and pressure transducer connected to the airway opening. 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.

  5. Change in Respiratory Muscle Endurance Test at Screening, Baseline, and Day 180 [ Time Frame: Change from Screening, Baseline, and Day 180 ]
    This test will begin after subjects rest for a minimum of one hour. Subjects will be tested in the seated position while breathing through a mouthpiece with nose clip. When a steady state breathing pattern has been reached (noted by stable tidal volumes for at least 30 seconds), subjects will be instructed how to maintain the breathing rate and volume, with the use of visual feedback on a computer. A threshold inspiratory load equivalent to 35% of the maximal inspiratory pressure will be placed on the inspiratory port of the mouthpiece. Subjects will be instructed to maintain the established breathing pattern during loaded breathing. The test will end when the subject cannot open the threshold valve for 3 consecutive breaths, or when the subject can no longer subjectively tolerate the test and must remove the mouthpiece. Loaded breathing typically lasts between 2-10 minutes.

  6. Change in Electromyogram (EMG) at Baseline, Day 3, Day 14, and Day 180 [ Time Frame: Change from Baseline, Day 3, Day 14, and 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.complete at least 30-minute bouts of paced SB, then the focus of breathing trials will be reduced pressure support mechanical ventilation.

  7. Change in Severe Respiratory Insufficiency Questionnaire at Screening, Baseline, Day 90, and Day 180 [ Time Frame: Change from Screening, baseline, Day 90 and Day 180 ]
    This questionnaire was developed for use in subjects with respiratory failure from various etiologies who utilize mechanical ventilation. It is a self administered test that will require approximately 20 minutes to complete.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   2 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Subjects with Pompe disease who are eligible for NeuRx DPS implantation
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02354651


Contacts
Contact: Barbara K Smith, PT, PhD 352-294-5315 bksmith@phhp.ufl.edu

Locations
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Barbara K Smith, PT, PhD    352-294-5315    bksmith@phhp.ufl.edu   
Sponsors and Collaborators
University of Florida
Acid Maltase Deficiency Association
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Barbara K Smith, PT, PhD University of Florida

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02354651     History of Changes
Other Study ID Numbers: IRB201600161-N
003-2013 ( Other Identifier: University of Florida pre-conversion )
1R21HD090752-01 ( U.S. NIH Grant/Contract )
First Posted: February 3, 2015    Key Record Dates
Last Update Posted: April 27, 2018
Last Verified: April 2018

Keywords provided by University of Florida:
Pompe disease
mechanical ventilation
diaphragm pacing

Additional relevant MeSH terms:
Glycogen Storage Disease Type II
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
Glycogen Storage Disease
Carbohydrate Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases