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NCT Number: NCT04658498

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

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.

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Key information

Conditions

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Hospital Leuven

Leuven, 3000, Belgium

Location status: Recruiting

Location contact

Daniel Langer

CONTACT

[email protected]

Daniel Langer, PT, PhD

PRINCIPAL_INVESTIGATOR

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Procedure: Usual Care (UC)

Other

Intermittent spontaneous breathing periods

Procedure: UC + HI-IMT

Other

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.

Procedure: UC + LI-IMT (sham IMT)

Other

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).

Primary outcomes

  1. Maximal Inspiratory Pressure (PImax)

    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.

Secondary outcomes

  1. Diaphragm mobility, thickness and thickening fraction by ultrasounds

    Time frame: Maximal duration of IMT treatment: 28 days

    Assessment by diaphragm ultrasounds

  2. Change in contractile material and structural alteration of sternocleidomastoid muscle

    Time frame: Maximal duration of IMT treatment: 28 days

    By analyzing muscle microbiopsies using Hematoxylin & Eosin (H&E) staining.

  3. Change in fiber proportion of sternocleidomastoid muscle fibers

    Time frame: Maximal duration of IMT treatment: 28 days

    By analyzing muscle microbiopsies with immunostaining of the myosin heavy chain.

  4. Change in size of sternocleidomastoid muscle fibers

    Time frame: Maximal duration of IMT treatment: 28 days

    By analyzing muscle microbiopsies with immunostaining of the myosin heavy chain.

  5. Change in amount of satellite cells of sternocleidomastoid muscle

    Time frame: Maximal duration of IMT treatment: 28 days

    By analyzing muscle microbiopsies with Pax7 immunostaining

  6. Change in amount of fibrotic tissue of sternocleidomastoid muscle

    Time frame: Maximal duration of IMT treatment: 28 days

    By analyzing muscle microbiopsies with Masson staining

  7. Change of gene expression of atrophy/hypertrophy related pathways of sternocleidomastoid muscle

    Time frame: Maximal duration of IMT treatment: 28 days

    By analyzing muscle microbiopsies with RT2 profiler PCR array skeletal muscle, Qiagen

  8. Change in cell proliferation of sternocleidomastoid muscle

    Time frame: Maximal duration of IMT treatment: 28 days

    By analyzing muscle microbiopsies cell proliferation assays

  9. Change in cell differentiation of sternocleidomastoid muscle

    Time frame: Maximal duration of IMT treatment: 28 days

    By analyzing muscle microbiopsies cell differentiation assays

  10. Change in Blood Flow Index (BFI) of extra-diaphragmatic respiratory muscles

    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.

  11. Change in Tissue Oxygenation Index (TOI) of ex of extra-diaphragmatic respiratory 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

  12. Change in signal amplitude of diaphragm electromyography

    Time frame: Maximal duration of IMT treatment: 28 days

    Diaphragm electromyography will be collected with an esophageal electrode catheter

  13. Change in signal amplitude of electromyography of extra-diaphragmatic respiratory muscles

    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

  14. Esophageal and gastric pressure

    Time frame: Maximal duration of IMT treatment: 28 days

    Using a multifunction nasogastric catheter

Study contacts

Contact information is provided by the study sponsor or research team.

Daniel Langer, PT, PhD

CONTACT

[email protected]

+3216330192

Sponsors and collaborators

Lead sponsor

KU Leuven

Other

Registry information

Acronym: TrainToWean

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Dec 8, 2020
Registry last updated
Mar 18, 2026

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.

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