University Hospital Leuven
Leuven, 3000, Belgium
Location status: Recruiting
NCT Number: NCT04658498
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.
Interested in participating?
Request Info18 year and older
All sexes
Interventional
Not applicable
Leuven, 3000, Belgium
Location status: Recruiting
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.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Intermittent spontaneous breathing periods
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.
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).
Time frame: Maximal duration of IMT treatment: 28 days
Using a unidirectional valve which will be connected to the patient's tracheostomy tube or endotracheal tube for an uninterrupted period of 25 seconds.
Time frame: Maximal duration of IMT treatment: 28 days
Assessment by diaphragm ultrasounds
Time frame: Maximal duration of IMT treatment: 28 days
By analyzing muscle microbiopsies using Hematoxylin & Eosin (H&E) staining.
Time frame: Maximal duration of IMT treatment: 28 days
By analyzing muscle microbiopsies with immunostaining of the myosin heavy chain.
Time frame: Maximal duration of IMT treatment: 28 days
By analyzing muscle microbiopsies with immunostaining of the myosin heavy chain.
Time frame: Maximal duration of IMT treatment: 28 days
By analyzing muscle microbiopsies with Pax7 immunostaining
Time frame: Maximal duration of IMT treatment: 28 days
By analyzing muscle microbiopsies with Masson staining
Time frame: Maximal duration of IMT treatment: 28 days
By analyzing muscle microbiopsies with RT2 profiler PCR array skeletal muscle, Qiagen
Time frame: Maximal duration of IMT treatment: 28 days
By analyzing muscle microbiopsies cell proliferation assays
Time frame: Maximal duration of IMT treatment: 28 days
By analyzing muscle microbiopsies cell differentiation assays
Time frame: Maximal duration of IMT treatment: 28 days
Measured 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.
Time frame: Maximal duration of IMT treatment: 28 days
Measured by near-infrared spectroscopy with optodes transcutaneously positioned on the scalene, sternocleidomastoid and upper rectus abdominis muscles
Time frame: Maximal duration of IMT treatment: 28 days
Diaphragm electromyography will be collected with an esophageal electrode catheter
Time frame: Maximal duration of IMT treatment: 28 days
Electromyography of scalene, sternocleidomastoid, parasternal intercostal and rectus abdominis muscles will be collected through surface electromyography electrodes
Time frame: Maximal duration of IMT treatment: 28 days
Using a multifunction nasogastric catheter
Contact information is provided by the study sponsor or research team.
KU Leuven
Other
Acronym: TrainToWean
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
Published trials that share one or more normalized conditions with this study.
NCT07363902
VIDD, Ventilator-induced Diaphragm Dysfunction
Barcelona, Spain
View Trial DetailsNCT07105202
Mechanical Ventilation, Weaning Failure
Arnhem, Gelderland, Netherlands
View Trial DetailsNCT07109570
Critical Illness, Diaphragm Electrical Activity
Leiden, Netherlands
View Trial DetailsNCT07003672
Weaning Failure
Taipei, Taiwan
View Trial Details