Mechanical Insufflator/Exsufflator Technique in Children With Neuromuscular Disease (MINEX-2)

Mechanical INsufflator/EXsufflator Technique in Paediatric Subjects With Neuromuscular Disease: a Randomised Crossover Comparison of 2 Modes of Application

In a randomized cross-over design, two different modes of a mechanical insufflator/exsufflator applied to pediatric subjects with neuromuscular disease will be compared with respect to their short term effect on lung function, i.e. lung volume.

Study Overview

• Status: Completed
• Conditions: Neuromuscular Diseases in Children
• Intervention / Treatment: Device: Mechanical insufflation/exsufflation conventional; Device: Mechanical insufflation/exsufflation modified

Detailed Description

At two consecutive regular outpatient clinic visits, each participant will perform a session of the insufflation/exsufflation technique.

Participants will be randomised by a computer-generated code to one of the two sequences (CON-MOD or MOD-CON) using sealed envelopes. The randomisation list will be generated by a study nurse of the Department of Paediatrics who is not a member of the study group.

The randomisation envelope will be opened by the treating physiotherapist immediately before the first treatment session.

Standardised intervention

At randomisation, the measurement belt of the EIT system will be fitted around the chest of the participant. Once correct fit is confirmed, the baseline measurement (T0) will be taken. After the baseline assessment, the participants will perform the conventional (CON) or modified (MOD) insufflator/exsufflator therapy session under supervision of a physiotherapist. In teh investigator's institution a therapy session consists of 5 series of 5 insufflation/exsufflation manoeuvres each (Cough assist E70, Philips Respironics, Hamburg, Germany). Positive and negative pressures will be set at the individual level of each subject.

Measurements Changes in lung volume and ventilation distribution will be assessed by electrical impedance tomography (EIT). These parameters will be obtained five minutes before (T0) and five, ten, twenty, forty and sixty minutes after the treatment session (T1 - T5). Measurements of 3 minutes will be recorded at each time point. Additionally EIT measurements will be performed continuously during the treatment session.

Electrical Impedance Tomography (EIT) is a non-invasive, radiation-free technique for the assessment of spatial and temporal ventilation distribution based on the changes in electrical properties of the tissue during the respiratory cycle. EIT measurements will be performed using a commercially available setup (PulmoVista 500, Draeger, Germany). Image reconstruction will be performed with the GREIT-algorithm using the torso mesh function. [Adler, 2009] Relative change in end-expiratory lung impedance (EELI) and the global inhomogeneity (GI) index, a measure of ventilation inhomogeneity, will be calculated using customized software (Matlab® R2021b, The MathWorks Inc., Nattick, MA, USA).

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • BE
    • Bern, BE, Switzerland, 3010
      • Inselspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 16 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of a NMD
• Functional status: non-ambulatory
• Age >5 years and < 16 years
• Able to cooperate
• Daily home-use of cough assist as reported by the caregivers
• Written informed consent by the subject/caregiver

Exclusion Criteria:

• Acute respiratory infection at two consecutive outpatient clinic visits (marked increase in cough, change in sputum amount or colour, fever or malaise)
• Oxygen dependency (defined as need for oxygen to achieve a transcutaneous oxygen saturation of ≥92%)
• Skin lesions at the chest (preventing EIT measurements)
• Chest deformation preventing EIT measurements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional settings first, modified settings second; The control intervention (CON) is the conventional mode of a commercially available mechanical insufflator/exsufflator. The manoeuvre consists of 5 sets of 5 mechanical insufflations/exsufflations with individual pressure settings. For the study, the same pressure settings will be used as during daily routine. The study intervention (MOD) is a modified mode of a commercially available mechanical insufflator/exsufflator in which the active exsufflation of the last breath of each set will be omitted. The manoeuvre consists of 5 sets of 5 mechanical insufflations/exsufflations with individual pressure settings. For the study, the same pressure settings will be used as during daily routine. This modified mode is already used in daily routine by a minority of subjects with NMD.	Device: Mechanical insufflation/exsufflation conventional; Conventional settings in a commercially available chest physiotherapy device; Device: Mechanical insufflation/exsufflation modified; Modified settings in a commercially available chest physiotherapy device
Experimental: Modified settings first, conventional settings second; The study intervention (MOD) is a modified mode of a commercially available mechanical insufflator/exsufflator in which the active exsufflation of the last breath of each set will be omitted. The manoeuvre consists of 5 sets of 5 mechanical insufflations/exsufflations with individual pressure settings. For the study, the same pressure settings will be used as during daily routine. This modified mode is already used in daily routine by a minority of subjects with NMD. The control intervention (CON) is the conventional mode of a commercially available mechanical insufflator/exsufflator. The manoeuvre consists of 5 sets of 5 mechanical insufflations/exsufflations with individual pressure settings. For the study, the same pressure settings will be used as during daily routine.	Device: Mechanical insufflation/exsufflation conventional; Conventional settings in a commercially available chest physiotherapy device; Device: Mechanical insufflation/exsufflation modified; Modified settings in a commercially available chest physiotherapy device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in end-expiratory lung impedance from baseline	Change of end-expiratory lung volume estimated by electrical impedance tomography from baseline to immediately after a session of mechanical insufflation/exsufflation.	3-5 Minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ventilation distribution from baseline	Differences in ventilation distribution assessed with electrical impedance tomography from baseline to immediately after a session of mechanical insufflation/exsufflation.	3-5 Minutes
Duration of effect	Duration of the postulated effect on lung volume assessed by electrical impedance tomography.	15-20 minutes

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Study Director: Thomas Riedel, MD, Inselspital, Bern University Hospital

Publications and helpful links

General Publications

• Casaulta C, Messerli F, Rodriguez R, Klein A, Riedel T. Changes in ventilation distribution in children with neuromuscular disease using the insufflator/exsufflator technique: an observational study. Sci Rep. 2022 Apr 29;12(1):7009. doi: 10.1038/s41598-022-11190-z.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Actual): December 7, 2024
• Study Completion (Actual): December 20, 2024

Study Registration Dates

• First Submitted: July 6, 2022
• First Submitted That Met QC Criteria: July 6, 2022
• First Posted (Actual): July 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 6, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Lung function
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases
• Other Study ID Numbers: MINEX-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD sharing upon request
• IPD Sharing Time Frame: Available from time of publication for up to two years
• IPD Sharing Access Criteria: email: thomas.riedel@insel.ch
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No