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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: Uni- and bilateral magnetic phrenic nerve stimulation

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • ZH
    • Zurich, ZH, Switzerland, 8057
      • Exercise Physiology Lab, Institute of Human Movement Sciences and Sport, ETH Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 31 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Magnetic Phrenic Nerve Stimulation; 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; Uni- and bilateral magnetic phrenic nerve stimulation using different coils, stimulation patterns (frequency, intensity, number of pulses) and locations (neck, chest).

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Swiss Federal Institute of Technology

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2019
• Primary Completion (Actual): July 15, 2020
• Study Completion (Actual): July 15, 2020

Study Registration Dates

• First Submitted: November 19, 2019
• First Submitted That Met QC Criteria: November 21, 2019
• First Posted (Actual): November 25, 2019

Study Record Updates

• Last Update Posted (Actual): August 12, 2020
• Last Update Submitted That Met QC Criteria: August 11, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: OPTISTIM_2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No