Muscle Recruitment During Neck Flexion and Inspiratory Muscle Training (FLEX)

May 15, 2025 updated by: Unity Health Toronto

Muscle Recruitment During Neck Flexion and Inspiratory Muscle Training in Difficult and Prolonged Weaning Patients: a Physiological Study - The FLEX Study

Respiratory muscle dysfunction is highly prevalent in patients with prolonged weaning from mechanical ventilation and is strongly associated with weaning failure. Efforts to strengthen the respiratory muscles, aimed at reversing or minimizing the impact of respiratory muscle weakness on clinical outcomes, have generally focused on the diaphragm with specific inspiratory muscle training (IMT) exercises. However, the effectiveness of these exercises and impact on clinical outcomes are not current practice in the majority of ICUs, as they are hardly feasible in ICU patients who often cannot be disconnected from the ventilator and cannot fully cooperate.

Promising results have been published concerning non-respiratory training techniques, which can also target the accessory muscles, particularly important in the presence of increased load to the respiratory system, as in the case of the weaning phase. These non-respiratory training techniques would have the advantage of not entailing disconnection of the patient from the ventilator. In particular, in healthy subjects, a quasi-isometric neck contraction, called neck flexion, appeared to generate greater or comparable recruitment of some principal and accessory muscles of respiration, when compared to conventional IMT. However, this has not been studied in patients requiring prolonged mechanical ventilation, for whom IMT with threshold loading devices remains the primary recommended rehabilitation strategy.

Therefore, the primary aim of the investigators is to assess the feasibility, tolerability, and safety of neck flexion and to compare them with IMT technique in patients with difficult and prolonged weaning from mechanical ventilation. Secondary aims are: i) to characterize which respiratory muscles are recruited and their level of activation at different levels of ventilatory assistance and ii) to assess which respiratory muscles are recruited and their level of activation during the two techniques and to compare these findings.

The hypothesis of the investigators is that neck flexion will be feasible (more than conventional IMT), well tolerated, and safe in patients with difficult and prolonged weaning. The investigators also hypothesize that, reducing the level of assistance and during unassisted breathing, a progressively increasing activation of the diaphragm, neck and trunk respiratory muscles, reflecting increased ventilatory load, will be fund. Finally, the hypothesis of the investigators is that the level of muscle activation/recruitment during neck flexion will be comparable or even greater to that occurring during IMT, as found in healthy subjects.

Finding a new and highly feasible rehabilitative technique, able to recruit and train the respiratory muscles (including accessory muscles), will have the potential to promote patients' weaning and improve all related clinical outcomes, and therefore to dramatically shift the paradigm about the role of rehabilitation in ICU.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The investigators will conduct a prospective longitudinal pilot study in patients receiving mechanical ventilation via endotracheal tube or tracheostomy.

The investigators will perform a set of baseline measurements (as early as possible after the patient reaches the ability to spontaneously trigger the ventilator).These measurements include: I) ultrasound measurements (thickness and thickening fraction) of the diaphragm, parasternal intercostals, sternocleidomastoid and of the abdominal muscles; II) surface electromyography (sEMG) of the diaphragm, sternocleidomastoid, scalene, and of the abdominal muscles. Ultrasound and sEMG measurements will be performed during the current level of ventilation (decided by the clinical team), during minimal level of ventilatory support and/or during unassisted breathing; III) maximal inspiratory pressure (MIP); IV) maximal voluntary contraction (MVC) of neck flexion.

As soon as patients can be disconnected from the ventilator I) IMT maneuvers and II) neck flexion maneuvers, will be started and performed once a week (each time in a randomized order), until patients are successfully weaned or for a maximum of 4 weeks. The investigators will also perform: III) ultrasound measurements; IV) surface electromyography of the muscles above specified during each IMT and neck flexion maneuver; V) MIP and MVC; these latter measurements will be repeated weekly and inspiratory muscle training and neck flexion intensity level targeted accordingly.

Study Type

Interventional

Enrollment (Estimated)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5B 1W8
        • Recruiting
        • St. Michael's Hospital
        • Principal Investigator:
          • Laurent Brochard
        • Sub-Investigator:
          • Antenor Rodrigues
        • Contact:
        • Sub-Investigator:
          • Annia Schreiber
        • Sub-Investigator:
          • Vorakamol Phoophiboon

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients receiving invasive MV via endotracheal tube who had failed a planned extubation or failed at least three spontaneous breathing trials (SBTs) or receiving MV via tracheostomy (who required tracheostomy because of difficult or prolonged weaning, failed extubation and/or prolonged ventilation) and able to spontaneously trigger the ventilator.
  • Over or equal to 16 years of age
  • Tolerating levels of pressure support of 10 cmH2O or lower (or equivalent support in NAVA or PAV+) for at least 15 minutes
  • In stable clinical and hemodynamic conditions and adequate level of oxygenation (cardiac frequency ≤ 140 beats/minute, systolic blood pressure 90-160 mmHg, no or minimal vasopressors, PaO2/FiO2 over or equal to 150 mmHg)
  • Able to understand and follow simple verbal instructions

Exclusion Criteria:

  • Patients with a previously diagnosed severe neuromuscular disorder (such as amyotrophic lateral sclerosis, muscular dystrophy, multiple sclerosis, myasthenia gravis or spinal cord injury)
  • Patients with chronic respiratory failure already ventilated before ICU admission
  • Patients unable to collaborate or understand instructions

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Quasi-Isometric Neck Flexion

On minimal mechanical ventilation support (unassisted/assisted spontaneous breathing) via tracheostomy.

Quasi-Isometric Neck Flexion will be performed during mechanical ventilation. Patients will be asked to minimally lift their head from the pillow generating a quasi-isometric neck contraction. 30% will be the target intensity level for neck flexion. The patient will perform 2 sets of 6-10 quasi-isometric neck flexions.
Other: Quasi-Isometric Neck Flexion
Patients will be asked to minimally lift their head from the pillow generating a quasi-isometric neck contraction (2 sets of 6-10 flexions).
Other: Inspiratory Muscle Training

Patients will be asked to complete 2 sets of 6-10 breaths through a POWERbreathe device, which applies a variable resistance provided by an electronically controlled valve (variable flow resistive load).

During each IMT and neck flexion maneuver ultrasound measurements will be performed (measurements of the diaphragm, sternocleidomastoid, parasternal intercostal, internal oblique [IO], external oblique [EO], transversus abdominis [TrA] and rectus abdominis [RA] will be taken) and, during the entire period, sEMG monitoring of the target muscles (diaphragm, sternocleidomastoid, parasternal intercostal and EO) will be continued.
Experimental: Inspiratory Muscle Training
Perform 2 sets of 6-10 breaths through a POWERbreathe device, which applies a variable resistance provided by an electronically controlled valve (variable flow resistive load). The training device will be set at 30% of the highest value of three MIP maneuvers. A two-minute rest period with MV support will be provided between each set.
Other: Quasi-Isometric Neck Flexion
Patients will be asked to minimally lift their head from the pillow generating a quasi-isometric neck contraction (2 sets of 6-10 flexions).
Other: Inspiratory Muscle Training

Patients will be asked to complete 2 sets of 6-10 breaths through a POWERbreathe device, which applies a variable resistance provided by an electronically controlled valve (variable flow resistive load).

During each IMT and neck flexion maneuver ultrasound measurements will be performed (measurements of the diaphragm, sternocleidomastoid, parasternal intercostal, internal oblique [IO], external oblique [EO], transversus abdominis [TrA] and rectus abdominis [RA] will be taken) and, during the entire period, sEMG monitoring of the target muscles (diaphragm, sternocleidomastoid, parasternal intercostal and EO) will be continued.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adherence to the training techniques
Time Frame: Baseline measurements assessed ≤ 72 hours from admission and once a week until successfully weaned or up to maximum of 4 weeks.
Adherence to neck flexion and inspiratory muscle training techniques (minimum 70% completion), corresponding to the number of training sessions divided by the total number of potential sessions.
Baseline measurements assessed ≤ 72 hours from admission and once a week until successfully weaned or up to maximum of 4 weeks.
Incidence of Treatment-Emergent Adverse Events
Time Frame: Baseline measurements assessed ≤ 72 hours from admission and once a week until successfully weaned or up to maximum of 4 weeks.

Neck flexion and IMT will be considered well tolerated if < 10% of patients refers dyspnea > 6 on the Borg scale (Borg scale minimum value is 0, which corresponds to no breathlessness at all; maximum value is 10, corresponding to the most severe breathlessness ever experienced or could imagine experiencing), or severe musculoskeletal soreness, during/after the training techniques.

Neck flexion and IMT will be considered safe if < 5% of adverse events will be observed during/after the training techniques. Will be considered adverse events: desaturation over 4%, systolic blood pressure >180 mmHg or <90 mmHg or increased over or equal to 20%, cardiac arrhythmias, heart rate >140 beats/min or increased over or equal to 20%, respiratory rate >35 breaths/min or increased over or equal to 50%, cyanosis, diaphoresis, dizziness, facial signs of distress, evidence of increasing accessory muscle activity.
Baseline measurements assessed ≤ 72 hours from admission and once a week until successfully weaned or up to maximum of 4 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Level of activation of the different respiratory muscles at different levels of ventilatory assistance through surface EMG
Time Frame: As early as possible after reaching the ability to spontaneously trigger the ventilator and tolerate a pressure support value of 10 cmH2O or below for at least 15 minutes until successfully weaned or a maximum of 4 weeks
• To compare the level of activation during usual ventilatory setting vs minimal level of assistance/unassisted breathing paired t-test or Wilcoxon test will be performed.
As early as possible after reaching the ability to spontaneously trigger the ventilator and tolerate a pressure support value of 10 cmH2O or below for at least 15 minutes until successfully weaned or a maximum of 4 weeks
Level of activation of the different respiratory muscles at different levels of ventilatory assistance through ultrasound
Time Frame: As early as possible after reaching the ability to spontaneously trigger the ventilator and tolerate a pressure support value of 10 cmH2O or below for at least 15 minutes until successfully weaned or a maximum of 4 weeks
• To compare the level of activation during usual ventilatory setting vs minimal level of assistance/unassisted breathing paired t-test or Wilcoxon test will be performed.
As early as possible after reaching the ability to spontaneously trigger the ventilator and tolerate a pressure support value of 10 cmH2O or below for at least 15 minutes until successfully weaned or a maximum of 4 weeks
Level of activation of the different respiratory muscles during the two training techniques (quasi-isometric neck flexion and IMT) through surface EMG
Time Frame: As early as possible after reaching the ability to spontaneously trigger the ventilator and tolerate a pressure support value of 10 cmH2O or below for at least 15 minutes until successfully weaned or a maximum of 4 weeks
• To compare the degree of activation during IMT and neck flexion paired t-test or Wilcoxon test will be performed.
As early as possible after reaching the ability to spontaneously trigger the ventilator and tolerate a pressure support value of 10 cmH2O or below for at least 15 minutes until successfully weaned or a maximum of 4 weeks
Level of activation of the different respiratory muscles during the two training techniques (quasi-isometric neck flexion and IMT) through ultrasound
Time Frame: As early as possible after reaching the ability to spontaneously trigger the ventilator and tolerate a pressure support value of 10 cmH2O or below for at least 15 minutes until successfully weaned or a maximum of 4 weeks
• To compare the degree of activation during IMT and neck flexion paired t-test or Wilcoxon test will be performed.
As early as possible after reaching the ability to spontaneously trigger the ventilator and tolerate a pressure support value of 10 cmH2O or below for at least 15 minutes until successfully weaned or a maximum of 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Unity Health Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 9, 2023

Primary Completion (Estimated)

November 15, 2025

Study Completion (Estimated)

November 15, 2025

Study Registration Dates

First Submitted

December 19, 2022

First Submitted That Met QC Criteria

January 23, 2023

First Posted (Actual)

February 2, 2023

Study Record Updates

Last Update Posted (Estimated)

May 20, 2025

Last Update Submitted That Met QC Criteria

May 15, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22-185

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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