Neuromuscular DiseasesMIE and EITNCT02753959
Changes in Regional Lung Ventilation Following Mechanical Insufflation-Exsufflation
A study testing Acute Intervention and Stable Intervention in people with Neuromuscular Diseases, run by Guy's and St Thomas' NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Patients with NMD can suffer from a range of respiratory problems due to respiratory muscle weakness. Cough muscle weakness worsens secretion clearance from the airways, and increases the risk of infection. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Neuromuscular Diseases
- What is being tested?
- Acute Intervention and Stable Intervention
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Aug 2016to 30 Sep 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Neuromuscular disease e.g. muscular dystrophy, motor neurons disease
- Respiratory muscle weakness (FVC <60%, snip <60%, sleep disordered breathing)
- Clinical evidence of respiratory secretions or cough PEF <270 and history of LRTI
- Documented clinical stability by supervising clinician
- Neuromuscular disease e.g. muscular dystrophy, motor neurons disease
- Respiratory muscle weakness (FVC <60%, snip <60%, sleep disordered breathing)
- Clinical evidence of respiratory secretions or cough PEF <270
- Admitted with respiratory deterioration
Who cannot join
- Decompensated respiratory failure (pH < 7.35)
- Pregnancy
- Aged <18, >80
- Change in ventilator settings in preceding 4 weeks
- Significant physical or psychiatric co-morbidity that would prevent compliance with trial protocol
- Decompensated respiratory failure (pH < 7.35), at time of recruitment
Show all 9Show fewer
- Pregnancy
- Aged <18, >80
- Significant physical or psychiatric co-morbidity that would prevent compliance with trial protocol
Trial locations and contacts
1 site in 1 country.
About this study
Patients with NMD can suffer from a range of respiratory problems due to respiratory muscle weakness. Cough muscle weakness worsens secretion clearance from the airways, and increases the risk of infection. As a result, these patients often require chest physiotherapy or are supported with devices to aid clearance (such as mechanical insufflation-exsufflation) to reduce the risk of infection. Although evidence supports the use of these devices, the optimal technique or settings on the device are not clear.
Electrical impedance tomography (EIT) is a new technology that involves wearing a belt of sensors around the chest that provides information on how well the lungs are being filled with air. It allows a non-invasive assessment of the effect of each secretion clearance technique on lung ventilation in real-time.
This study aims to compare how well the lung is filled with air between three different techniques for secretion clearance (clearing mucus and phlegm from the airways), in order to determine which of the techniques is the most effective, in patients with NMD.
Read the detailed description
Electrical Impedance Tomography (EIT) is a non-invasive, bedside monitoring technique that provides semi-continuous, real-time information about the regional distribution of the changes in electrical resistivity of the lung tissue due to variations in ventilation in relation to a reference state.
Information is gained by repeatedly injecting small alternating electric currents (usually 5 mA) at high frequency of 50 - 80 kHz through a system of skin electrodes (usually 16) applied circumferentially around the thorax in a single plane between the 4th and 6th intercostal space. While an adjacent pair of electrodes 'injects' the current ('adjacent drive configuration'), all the remaining adjacent passive electrode pairs measure the differences in electric potential. A resistivity (impedance) image is reconstructed from this data by a mathematical algorithm using a two dimensional model and a simplified shape to represent the thoracic cross-section.
The resulting image possesses a high temporal and functional resolution making it possible to monitor dynamic physiological phenomena (e.g., delay in regional inflation or recruitment) on a breath by breath basis. It is important to realize that the EIT images are based on image reconstruction techniques that require at least one measurement on a well-defined reference state. All quantitative data are related to this reference and can only indirectly quantify (relative) changes in local lung impedance (but not absolute).
Patients with respiratory muscle weakness have reduced cough strength and this can cause difficulties with clearing respiratory secretions. This impaired secretion clearance can lead to respiratory infections and acutely can causing small airway occlusion with subsequent ventilation-perfusion mismatch adversely effecting pulmonary mechanics. The use of cough assist devices, such as mechanical insufflation-exsufflation (MIE) can improve secretion clearance. Although there is evidence that these devices can improve secretion clearance the optimal pressures or technique required to provide effective secretion clearance is not known. Furthermore the use of high pressure swings that are now frequently used in clinical practice could lead to lung derecruitment. The use of EIT would allow a novel and effective method of assessing the ability to clear secretions and optimise ventilated lung in neuromuscular patients with poor cough and assess post procedure derecruitment.
MIE: A pilot physiological study will be performed in patients with neuromuscular disease with acute (10 patients) and chronic (10 patients) secretion management issues that require clinical use of MIE. These patients will be studied using 3 different clearance strategies low pressure MIE, higher pressure MIE and standard airway techniques. The project will assess differences in regional ventilation following augmented airway clearance and inform potential endpoints and feasibility for a larger trial regarding speed of recovery from respiratory infections in patients with neuromuscular disease.
There is a paucity of data regarding the physiological efficacy of MIE devices and although clinical consensus regards them as a beneficial adjunct to the management of patients with respiratory muscle weakness causing a reduction in effective secretion clearance it is less clear the optimum protocol to achieve secretion clearance. The aim of chest physiotherapy is to achieve clearance of airway secretions and allow improved gas exchange by enhancing ventilation and perfusion matching within the lung. The data suggesting optimum pressures for MIE are based around early work on achieving enhanced cough peak expiratory flow. More recently higher pressures have been suggested to achieve enhanced airway clearance. There may be potential beneficial effects with high pressure MIE by enhancing airway opening during the insufflation pressure achieving a degree of lung volume recruitment. Conversely, high insufflation pressures may adversely affect both pulmonary and cardiac physiology which may be further impacted by the large pressure swing during exsufflation. This is particularly relevant given the increasing co-morbid cardiomyopathy that occurs in many congenital neuromuscular diseases.
The initial phase of the project would be to generate pilot data with a comprehensive physiological evaluation of patients with neuromuscular disease and requirement of cough augmentation with MIE devices. The patients will undergo a randomised protocol of chest clearance with standard physio, low pressure and high pressure MIE. Data from this trial will allow an optimal treatment strategy to be developed and if data suggested would provide sufficient data to power an interventional trial to examine important clinical outcomes.
- Conditions
- Neuromuscular Diseases
- Being tested
- Acute Intervention, Stable Intervention
- Medical subject headings
- Neuromuscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acute InterventionOther
Patients will be set up onto their Non Invasive Ventilator and assessed for an hour prior to, during and following secretion clearance and will have the following assessed:
- Electrical impedance tomography (EIT)
- EMGpara
- SpO2
- tcCO2
- Respiratory inductance plethysmography
- EIT will be performed as 2 to 10-minutes recording of quiet breathing before and after each intervention
Interventions will be set as follows with a 30 minute washout period between modes:
- Manual techniques only
- MIE at low pressure (+30 to -30)
- MIE at high pressure (+60 to -60)
Stable InterventionOther
Patients will be set up onto their Non Invasive Ventilator and assessed for an hour prior to, during and following secretion clearance and will have the following assessed:
- Electrical impedance tomography (EIT)
- EMGpara
- SpO2
- tcCO2
- Respiratory inductance plethysmography
- EIT will be performed as 2 to 10-minutes recording of quiet breathing before and after each intervention
Interventions will be set as follows with a 30 minute washout period between modes:
- Manual techniques only
- MIE at low pressure (+30 to -30)
- MIE at high pressure (+60 to -60)
| Study group | Role | What they receive |
|---|---|---|
| Acute Intervention | Experimental | Patients will need to be Clinically stable patients with established neuromuscular disease with clinical secretions or cough PEF <270 and history of chest infections. Patients are required to be stable for the preceding 4 weeks with no changes to medications or ventilator settings. Receives: Other: Acute Intervention |
| Stable Intervention | Experimental | Patients with established neuromuscular disease admitted to either the Lane Fox Respiratory Unit or Critical Care at St Thomas' Hospital with acute respiratory deteriorations and with the need for respiratory physiotherapy for secretion management. Receives: Other: Stable Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in the regional ventilation delays and Increase in homogeneity of ventilation post MIE vs baseline.
Measured: 1 day
Secondary outcomes (3)
Change in neural respiratory drive (EMGpara) pre to post clearance
Change in neural respiratory drive (EMGpara) pre to post secretion clearance
Measured: 1 day
Change in gas exchange (SpO2 and tcCO2)
Change in gas exchange, measured by taking SpO2 measurements and tCO2 measurements before and after secretion clearance
Measured: 1 day
Subjective patient comfort (Visual analogue scale - VAS)
Change in patient comfort defined by VAS pre and post secretion clearance
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2016 (estimated)
- Study start1 Aug 2016
- Primary completion30 Sep 2019
- Study completion30 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuromuscular DiseasesStudies of the same condition, open and under way.
- More trials run by Guy's and St Thomas' NHS Foundation TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Guy's and St Thomas' NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- B&D Electromedical
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02753959
- Sponsor's protocol ID
- PM Mar 16
- Acronym
- MIE and EIT
- Status last verified
- Apr 2018
- First submitted
- 25 Apr 2016
- Last updated
- 10 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Shah NM, Apps C, Kaltsakas G, Madden-Scott S, Suh ES, D'Cruz RF, Arbane G, Patout M, Lhuillier E, Hart N, Murphy PB. The Effect of Pressure Changes During Mechanical Insufflation-Exsufflation on Respiratory and Airway Physiology. Chest. 2024 Apr;165(4):929-941. doi: 10.1016/j.chest.2023.10.015. Epub 2023 Oct 14.
PubMed 37844796
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Changes in Regional Lung Ventilation Following Mechanical Insufflation-Exsufflation
- ClinicalTrials.gov ID
- NCT02753959
- Acronym / sponsor ID
- MIE and EIT / PM Mar 16
- Conditions
- Neuromuscular Diseases
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Guy's and St Thomas' NHS Foundation TrustUniversity, hospital or other
- Collaborators
- B&D Electromedical
- Study start
- 1 Aug 2016 (actual)
- Primary completion
- 30 Sep 2019 (actual)
- Study completion
- 30 Sep 2019 (actual)
- First posted
- 28 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with NMD can suffer from a range of respiratory problems due to respiratory muscle weakness. Cough muscle weakness worsens secretion clearance from the airways, and increases the risk of infection. As a result, these patients often require chest physiotherapy or are supported with devices to aid clearance (such as mechanical insufflation-exsufflation) to reduce the risk of infection. Although evidence supports the use of these devices, the optimal technique or settings on the device are not clear.
Electrical impedance tomography (EIT) is a new technology that involves wearing a belt of sensors around the chest that provides information on how well the lungs are being filled with air. It allows a non-invasive assessment of the effect of each secretion clearance technique on lung ventilation in real-time.
This study aims to compare how well the lung is filled with air between three different techniques for secretion clearance (clearing mucus and phlegm from the airways), in order to determine which of the techniques is the most effective, in patients with NMD.
Detailed description
Electrical Impedance Tomography (EIT) is a non-invasive, bedside monitoring technique that provides semi-continuous, real-time information about the regional distribution of the changes in electrical resistivity of the lung tissue due to variations in ventilation in relation to a reference state.
Information is gained by repeatedly injecting small alternating electric currents (usually 5 mA) at high frequency of 50 - 80 kHz through a system of skin electrodes (usually 16) applied circumferentially around the thorax in a single plane between the 4th and 6th intercostal space. While an adjacent pair of electrodes 'injects' the current ('adjacent drive configuration'), all the remaining adjacent passive electrode pairs measure the differences in electric potential. A resistivity (impedance) image is reconstructed from this data by a mathematical algorithm using a two dimensional model and a simplified shape to represent the thoracic cross-section.
The resulting image possesses a high temporal and functional resolution making it possible to monitor dynamic physiological phenomena (e.g., delay in regional inflation or recruitment) on a breath by breath basis. It is important to realize that the EIT images are based on image reconstruction techniques that require at least one measurement on a well-defined reference state. All quantitative data are related to this reference and can only indirectly quantify (relative) changes in local lung impedance (but not absolute).
Patients with respiratory muscle weakness have reduced cough strength and this can cause difficulties with clearing respiratory secretions. This impaired secretion clearance can lead to respiratory infections and acutely can causing small airway occlusion with subsequent ventilation-perfusion mismatch adversely effecting pulmonary mechanics. The use of cough assist devices, such as mechanical insufflation-exsufflation (MIE) can improve secretion clearance. Although there is evidence that these devices can improve secretion clearance the optimal pressures or technique required to provide effective secretion clearance is not known. Furthermore the use of high pressure swings that are now frequently used in clinical practice could lead to lung derecruitment. The use of EIT would allow a novel and effective method of assessing the ability to clear secretions and optimise ventilated lung in neuromuscular patients with poor cough and assess post procedure derecruitment.
MIE: A pilot physiological study will be performed in patients with neuromuscular disease with acute (10 patients) and chronic (10 patients) secretion management issues that require clinical use of MIE. These patients will be studied using 3 different clearance strategies low pressure MIE, higher pressure MIE and standard airway techniques. The project will assess differences in regional ventilation following augmented airway clearance and inform potential endpoints and feasibility for a larger trial regarding speed of recovery from respiratory infections in patients with neuromuscular disease.
There is a paucity of data regarding the physiological efficacy of MIE devices and although clinical consensus regards them as a beneficial adjunct to the management of patients with respiratory muscle weakness causing a reduction in effective secretion clearance it is less clear the optimum protocol to achieve secretion clearance. The aim of chest physiotherapy is to achieve clearance of airway secretions and allow improved gas exchange by enhancing ventilation and perfusion matching within the lung. The data suggesting optimum pressures for MIE are based around early work on achieving enhanced cough peak expiratory flow. More recently higher pressures have been suggested to achieve enhanced airway clearance. There may be potential beneficial effects with high pressure MIE by enhancing airway opening during the insufflation pressure achieving a degree of lung volume recruitment. Conversely, high insufflation pressures may adversely affect both pulmonary and cardiac physiology which may be further impacted by the large pressure swing during exsufflation. This is particularly relevant given the increasing co-morbid cardiomyopathy that occurs in many congenital neuromuscular diseases.
The initial phase of the project would be to generate pilot data with a comprehensive physiological evaluation of patients with neuromuscular disease and requirement of cough augmentation with MIE devices. The patients will undergo a randomised protocol of chest clearance with standard physio, low pressure and high pressure MIE. Data from this trial will allow an optimal treatment strategy to be developed and if data suggested would provide sufficient data to power an interventional trial to examine important clinical outcomes.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acute Intervention | Experimental | Other: Acute InterventionPatients will need to be Clinically stable patients with established neuromuscular disease with clinical secretions or cough PEF <270 and history of chest infections. Patients are required to be stable for the preceding 4 weeks with no changes to medications or ventilator settings. |
| Stable Intervention | Experimental | Other: Stable InterventionPatients with established neuromuscular disease admitted to either the Lane Fox Respiratory Unit or Critical Care at St Thomas' Hospital with acute respiratory deteriorations and with the need for respiratory physiotherapy for secretion management. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Neuromuscular disease e.g. muscular dystrophy, motor neurons disease
- Respiratory muscle weakness (FVC <60%, snip <60%, sleep disordered breathing)
- Clinical evidence of respiratory secretions or cough PEF <270 and history of LRTI
- Documented clinical stability by supervising clinician
- Neuromuscular disease e.g. muscular dystrophy, motor neurons disease
Key exclusion criteria (9 listed)
- Decompensated respiratory failure (pH < 7.35)
- Pregnancy
- Aged <18, >80
- Change in ventilator settings in preceding 4 weeks
- Significant physical or psychiatric co-morbidity that would prevent compliance with trial protocol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acute InterventionPatients will be set up onto their Non Invasive Ventilator and assessed for an hour prior to, during and following secretion clearance and will have the following assessed: * Electrical impedance tomography (EIT) * EMGpara * SpO2 * tcCO2 * Respiratory inductance plethysmography * EIT will be performed as 2 to 10-minutes recording of quiet breathing before and after each intervention Interventions will be set as follows with a 30 minute washout period between modes: * Manual techniques only * MIE at low pressure (+30 to -30) * MIE at high pressure (+60 to -60) | Other | Acute Intervention |
| Stable InterventionPatients will be set up onto their Non Invasive Ventilator and assessed for an hour prior to, during and following secretion clearance and will have the following assessed: * Electrical impedance tomography (EIT) * EMGpara * SpO2 * tcCO2 * Respiratory inductance plethysmography * EIT will be performed as 2 to 10-minutes recording of quiet breathing before and after each intervention Interventions will be set as follows with a 30 minute washout period between modes: * Manual techniques only * MIE at low pressure (+30 to -30) * MIE at high pressure (+60 to -60) | Other | Stable Intervention |
Primary outcome
Reduction in the regional ventilation delays and Increase in homogeneity of ventilation post MIE vs baseline.
Time frame: 1 day
3 secondary outcomes
Change in neural respiratory drive (EMGpara) pre to post clearance
Time frame: 1 day
Change in gas exchange (SpO2 and tcCO2)
Time frame: 1 day
Subjective patient comfort (Visual analogue scale - VAS)
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2020.
- Derived from this study: PubMed 37844796Shah NM, Apps C, Kaltsakas G, Madden-Scott S, Suh ES, D'Cruz RF, Arbane G, Patout M, Lhuillier E, Hart N, Murphy PB. The Effect of Pressure Changes During Mechanical Insufflation-Exsufflation on Respiratory and Airway Physiology. Chest. 2024 Apr;165(4):929-941. doi: 10.1016/j.chest.2023.10.015. Epub 2023 Oct 14.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acute Intervention and Stable Intervention in people with Neuromuscular Diseases, run by Guy's and St Thomas' NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in the regional ventilation delays and Increase in homogeneity of ventilation post MIE vs baseline. (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02753959, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2020.