Optimization of Non-invasive Diaphragm Activation Using Magnetic Phrenic Nerve Stimulation

Study Overview
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Brief Summary
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The use of mechanical ventilation (MV) to replace spontaneous breathing has been associated with respiratory muscle dysfunction and lung injury from positive pressure. While using MV in an intensive care unit setting, the diaphragm is unloaded, potentially resulting in early development of diaphragmatic atrophy in as early as 18 hours of complete diaphragm inactivity. These changes in muscle properties result in a decrease in the force generating capability of the muscle, ultimately resulting in difficulty to restore spontaneous breathing and a subsequent prolonged weaning process or failure. A prolonged weaning period is associated with longer duration of MV, which may result in a cascade of further diaphragm dysfunction, weakness, and injury. Stimulation of the phrenic nerves to produce diaphragm contraction and activity is a possible mechanism to reduce MV related diaphragm dysfunction. Two promising studies have shown the potential of repetitive phrenic nerve stimulation on inducing diaphragm activity in human subjects with trains of pulses via both cervical and bilateral phrenic nerve stimulation. However, neither study provided optimal stimulation settings. As such, the primary purpose of this study is to investigate the optimal settings for noninvasive phrenic nerve stimulation to induce diaphragm contraction.

Official Title
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Optimization of Non-invasive Diaphragm Activation Using Magnetic Phrenic Nerve Stimulation

Conditions
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Healthy

Intervention / Treatment
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* Other: Uni- and bilateral magnetic phrenic nerve stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent as documented by signature Age: 18 - 35 years Non-smoking Healthy Able to communicate in English Normal lung function Normal Body mass index between 18.5 and 24.9 kg/m2 Willingness to adhere to the study rules Exclusion Criteria: Acute illness or chronic conditions affecting sleep or the performance of the respiratory, cardiovascular, neuromuscular, gastrointestinal or muscle system Women who are pregnant or breast feeding or have the intention to become pregnant during the course of the study Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant Known or suspected non-compliance, drug or alcohol abuse Intake of medication affecting sleep or the performance of the respiratory, cardiovascular or neuromuscular system or gastrointestinal or muscle system Presence of cardiac pacemaker, implanted defibrillators or implanted neurostimulators Any metal or electronics inside of the body History of seizures or epilepsy Tattoos on the stimulation sites Previous enrolment into the current study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Each participant enrolled in the study will be tested with different stimulation settings on three different days in a randomized order.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Magnetic Phrenic Nerve Stimulation<br>Each participant will be tested with 4 different stimulation setups (coils and stimulator) on 3 different days. | Other: Uni- and bilateral magnetic phrenic nerve stimulation<br>* Uni- and bilateral magnetic phrenic nerve stimulation using different coils, stimulation patterns (frequency, intensity, number of pulses) and locations (neck, chest).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in airflow | Flow will be recorded by a pneumotachometer and averaged over breaths. | Continuously measured from 10 sec before until 10 sec after each stimulation. One stimulation lasts for approx. 1 sec. | 
| Changes in costal diaphragm activity | Costal diaphragm activity will be continuously recorded via a wireless surface electromyography system. | Continuously measured from 10 sec before until 10 sec after each stimulation. One stimulation lasts for approx. 1 sec. | 
| Changes in transdiaphragmatic pressure | Transdiaphragmatic pressure changes, i.e. changes in esophageal and gastric pressures, will be measured by a pressure transducer connected to balloon-catheters. | Continuously measured from 10 sec before until 10 sec after each stimulation. One stimulation lasts for approx. 1 sec. | 
| Changes in mouth pressure | Mouth pressure will be continuously recorded using a differential pressure transducer. | Continuously measured from 10 sec before until 10 sec after each stimulation. One stimulation lasts for approx. 1 sec. | 
| Changes in abdominal movements | Abdominal movements will be assessed using the respiratory belt strain transducer. | Continuously measured from 10 sec before until 10 sec after each stimulation. One stimulation lasts for approx. 1 sec. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in extradiaphragmatic muscle activity | Muscle activity will be continuously recorded via a wireless surface electromyography system. | Continuously measured from 10 sec before until 10 sec after each stimulation. One stimulation lasts for approx. 1 sec. | 
| Changes in head, shoulder and arm movements | Head, shoulder and arm movements will be recorded using wireless acceleration sensors. | Continuously measured from 10 sec before until 10 sec after each stimulation. One stimulation lasts for approx. 1 sec. | 
| Changes in stress related parameters (heart rate, blood pressure, skin conductance) | Heart rate will will be continuously recorded with electrodes. Blood pressure will be continuously recorded using a non-invasive device. Skin conductance will be continuously recorded with electrodes worn on two fingers. | Continuously measured from 10 sec before until 10 sec after each stimulation. One stimulation lasts for approx. 1 sec. | 
| Perception of pain, paresthesia and distress | Participant subject perception of pain, paresthesia and distress will be evaluated with a visual analogue scales. | Assessed 10 sec after each stimulation. One stimulation lasts for approx. 1 sec. |