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Improving Our Understanding of Respiratory Muscle Training to Facilitate Weaning From Mechanical Ventilation in the ICU

Improving Our Understanding of Respiratory Muscle Training to Facilitate Weaning From Mechanical Ventilation in the ICU

Status
Recruiting
Phases
Unknown
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04658498
Acronym
TrainToWean
Enrollment
90
Registered
2020-12-08
Start date
2023-02-01
Completion date
2026-10-01
Last updated
2026-03-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Weaning Failure

Keywords

ICU acquired muscle weakness, IMT, Weaning outcomes, Maximal inspiratory pressure, Diaphragm EMG, Surface EMG, Diaphragm ultrasounds, Microbiopsies, Difficult to wean patients, Respiratory muscles

Brief summary

Mechanical ventilation is a life-saving treatment frequently applied in intensive care unit (ICU). Nonetheless, by putting at rest the respiratory muscles, it can lead to respiratory muscle weakness and atrophy, which are accompanied by prolonged duration of mechanical ventilation, difficult weaning and increased ICU mortality. Despite a strong theoretical rationale and some evidence supporting the use of inspiratory muscle training (IMT) to address respiratory muscle weakness and atrophy, the optimal approach to IMT remains largely uncertain. In fact, mechanistic studies evaluating physiological adaptations that occur in respiratory muscles of mechanically ventilated patients in response to different training regimens have not been conducted so far. The aim of this study is to comprehensively investigate changes in respiratory muscle function in response to three different conditions that patients will be exposed to during their period of weaning from mechanical ventilation.

Detailed description

A majority of mechanically ventilated patients develop respiratory muscle weakness during critical illness. The potential value of implementing rehabilitative interventions for respiratory muscle conditioning are supported by observations showing that respiratory muscle weakness is associated with prolonged duration of mechanical ventilation, difficult weaning, and increased ICU mortality. Despite a strong theoretical rationale and some evidence supporting its use, mechanistic studies evaluating physiological adaptations that occur in respiratory muscles of mechanically ventilated patients in response to different training regimens have not been performed so far. Consequently, the characterization of IMT modalities and of the optimal approach to IMT remain largely uncertain. To date, the great part of the studies on the topic employed an external mechanical threshold device to perform trainings, in general adopting loads ranging between 10-50% of maximal inspiratory strength (i.e. maximal inspiratory pressure (PImax)). Intermittent spontaneous breathing periods (e.g. using partially assisted or spontaneous modes of ventilation) are also frequently applied as an activating stimulus to the respiratory muscles during periods of mechanical ventilation. A tapered flow resistive load (TFRL) device (POWERbreathe KH2, HaB International, UK) has been already tested and implemented at University Hospital Leuven as a way of loading respiratory muscles in ICU patients. The TFRL approach represents a potential more optimal way of loading the respiratory muscles in patients on prolonged mechanical ventilation. Such a loading approach allows higher inspiratory tidal volumes to be reached and higher work and power generation during trainings, by adapting to changes in length-tension characteristics of the inspiratory muscles during inspiration. With regards to training modalities, high-intensity IMT modalities by applying loads ranging between 30 and 50 %PImax, have not yet been proven to be associated with better improvements in respiratory muscle strength compared to low-intensity (sham) IMT modalities at loads not exceeding 10 %PImax. On the other hand, no studies are available that assessed changes in respiratory muscle function beyond assessments of respiratory muscle strength in response to training. Additionally, no training studies have tried to quantify the intrinsic loading of the patients (i.e. elastic and resistive resistances of the chest wall and the lungs) that muscles are exposed to in between periods of additional loading applied during IMT sessions. The aim of this study is to comprehensively investigate changes in respiratory muscle function in response to three different conditions that difficult to wean patients will be exposed to during their weaning period. The complementary quantification of the entity of loading that respiratory muscles are bearing during assisted, spontaneous and resistive breathing would provide important novel insights on the optimization of IMT stimulus in different patients on prolonged mechanical ventilation.

Interventions

OTHERProcedure: Usual Care (UC)

Intermittent spontaneous breathing periods

OTHERProcedure: UC + HI-IMT

UC + Supervised daily sessions of training including 4 sets of 6-10 full vital capacity breaths against an external load using a tapered flow resistive device (POWERbreathe KH2, HaB International, UK). The maximum tolerable resistance allowing patients to inhale at least 70% of their inspiratory vital capacity will be chosen and progressively increased throughout the training period.

OTHERProcedure: UC + LI-IMT (sham IMT)

UC + superrvised daily sessions of training including 4 sets of 6-10 breaths at the lowest external imposable load with the tapered flow resistive device (POWERbreathe KH2, HaB International, UK) (i.e. 3 cmH2O).

Sponsors

KU Leuven
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)

Intervention model description

Double-blind, three arms parallel group randomized controlled trial with 1:1:1 allocation ratio

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Difficult and prolonged weaning patients * Adequate oxygenation * Febrile temperature \< 38ºC * Hemodynamic stability * Stable blood pressure * No or minimal vasopressors * No myocardial ischemia * Adequate hemoglobin and mentation * Resolution of disease acute phase * Able to follow simple verbal commands related to IMT * Mechanically ventilated via a tracheostomy or endotracheal tube

Exclusion criteria

* Pre-existing neuromuscular disease * Agitation * Hemodynamically instable (arrhythmia, decompensated heart failure, coronary insufficiency) * Hemoptysis * Diaphoresis * Spinal cord injury above T8 * Use of any type of home MV support prior to hospitalization * Skeletal pathology that impairs chest wall movements * Poor general prognosis or fatal outcome

Design outcomes

Primary

MeasureTime frameDescription
Maximal Inspiratory Pressure (PImax)Maximal duration of IMT treatment: 28 daysUsing a unidirectional valve which will be connected to the patient's tracheostomy tube or endotracheal tube for an uninterrupted period of 25 seconds.

Secondary

MeasureTime frameDescription
Change in size of sternocleidomastoid muscle fibersMaximal duration of IMT treatment: 28 daysBy analyzing muscle microbiopsies with immunostaining of the myosin heavy chain.
Diaphragm mobility, thickness and thickening fraction by ultrasoundsMaximal duration of IMT treatment: 28 daysAssessment by diaphragm ultrasounds
Change in contractile material and structural alteration of sternocleidomastoid muscleMaximal duration of IMT treatment: 28 daysBy analyzing muscle microbiopsies using Hematoxylin \& Eosin (H\&E) staining.
Change in fiber proportion of sternocleidomastoid muscle fibersMaximal duration of IMT treatment: 28 daysBy analyzing muscle microbiopsies with immunostaining of the myosin heavy chain.
Change in amount of satellite cells of sternocleidomastoid muscleMaximal duration of IMT treatment: 28 daysBy analyzing muscle microbiopsies with Pax7 immunostaining
Change of gene expression of atrophy/hypertrophy related pathways of sternocleidomastoid muscleMaximal duration of IMT treatment: 28 daysBy analyzing muscle microbiopsies with RT2 profiler PCR array skeletal muscle, Qiagen
Change in cell proliferation of sternocleidomastoid muscleMaximal duration of IMT treatment: 28 daysBy analyzing muscle microbiopsies cell proliferation assays
Change in cell differentiation of sternocleidomastoid muscleMaximal duration of IMT treatment: 28 daysBy analyzing muscle microbiopsies cell differentiation assays
Change in Blood Flow Index (BFI) of extra-diaphragmatic respiratory musclesMaximal duration of IMT treatment: 28 daysMeasured by near-infrared spectroscopy in combination with injections of the tracer indocyanine green dye (ICG), with optodes transcutaneously positioned on the scalene, sternocleidomastoid and upper rectus abdominis muscles.
Change in Tissue Oxygenation Index (TOI) of ex of extra-diaphragmatic respiratory musclesMaximal duration of IMT treatment: 28 daysMeasured by near-infrared spectroscopy with optodes transcutaneously positioned on the scalene, sternocleidomastoid and upper rectus abdominis muscles
Change in signal amplitude of diaphragm electromyographyMaximal duration of IMT treatment: 28 daysDiaphragm electromyography will be collected with an esophageal electrode catheter
Change in signal amplitude of electromyography of extra-diaphragmatic respiratory musclesMaximal duration of IMT treatment: 28 daysElectromyography of scalene, sternocleidomastoid, parasternal intercostal and rectus abdominis muscles will be collected through surface electromyography electrodes
Change in amount of fibrotic tissue of sternocleidomastoid muscleMaximal duration of IMT treatment: 28 daysBy analyzing muscle microbiopsies with Masson staining
Esophageal and gastric pressureMaximal duration of IMT treatment: 28 daysUsing a multifunction nasogastric catheter

Countries

Belgium

Contacts

CONTACTDaniel Langer, PT, PhD
daniel.langer@kuleuven.be+3216330192

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 19, 2026