Inspiratory Muscle Training in Lung Transplant Candidates

ConditionInspiratory Muscle Training

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age18+

SponsorUniversity Health Network, Toronto

About this trial

Recovery after lung transplantation (LTx) may be complicated by prolonged mechanical ventilation (MV) and protracted intensive care unit (ICU) stay leading to immobilization and impaired health-related quality of life (HRQoL). In the critical care setting, diaphragm atrophy and weakness have been associated with difficulty weaning from MV, increased risk for readmission to hospital or ICU, and increased mortality. Increasing respiratory muscle strength by inspiratory muscle training (IMT) as part of pre-rehabilitation mitigates respiratory muscle dysfunction peri-operatively and may reduce the risk of post-operative complications. However, IMT is not widely used prior to LTx and the benefits of pre-operative IMT on post-transplant outcomes in LTx candidates have not been studied. Objectives: (1) To evaluate the feasibility of a multicenter randomized clinical trial of IMT in LTx candidates in terms of recruitment rate, retention, program adherence, and outcome ascertainment; (2) To establish the change in pre-transplant dyspnea perception, diaphragm structure and function, health related quality of life (HRQoL) and post-transplant intensive care unit (ICU), hospital and post-transplant 3-month outcomes with IMT relative to usual care group; and (3) To characterize the effect of pre-transplant IMT on peri-transplant diaphragm myofibrillar cross-sectional area (CSA), oxidative capacity, inflammatory markers and post-transplant diaphragm muscle thickness and function (UHN TGH site).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adult participants (≥ 18 years of age)

Lung Transplant Candidates

Participating in outpatient pulmonary rehabilitation (standard of care)

Diagnosis of Interstitial Lung Disease or Chronic Obstructive Pulmonary Disease

Disqualifiers

Respiratory exacerbation within the last 1 month

Neurologic or musculoskeletal conditions that may interfere with IMT or functional assessments (i.e. history of stroke, severe arthritis of hands)

Insufficient English fluency to provide informed consent or to follow study protocols

Any evidence of pneumothorax on recent imaging (< 6 months)

Trial design

Design model

Parallel

Treatments tested in this trial

IMT and exercise training group
Other intervention
Participants will perform supervised exercise training per usual care and will be provided with a personalized prescription for an IMT program during the pre-transplant phase. Participants will perform two daily IMT sessions of 30 breaths (\< 5 minutes/session) 5 days per week in their home environment or in-person visits. IMT intensity will be progressed weekly by 5-10% of the baseline maximal inspiratory pressure if the Borg Dyspnea score is \< 7.

Treatment groups

90 Participants

are divided into 2 treatment groups

Group A: IMT and exercise training groupExperimental treatment 1 intervention

Group B: Usual care groupNo intervention 0 interventions

Trial outcomes

Primary outcomes

Study Recruitment According to Research Team Records

Recruitment-success percentage in the study will be assessed based on research team study records.

Time frame

Over study recruitment period (approximately 2 years)

Participant Retention in the Study According to Research Team Records

Participant retention will be assessed by measuring participant follow-up throughout the study period, according to research team records. A retention rate of 80% or greater (in each group) has been established as the criteria to determine study feasibility.

Time frame

Over the study data collection period (from enrolment until 3 months post-transplant)

Self-Reported Adherence to Inspiratory Muscle Training According to Participant IMT Diary

Adherence to inspiratory muscle training will be assessed via the IMT training diary completed by participants. Successful adherence will be defined as completion of ≥ 80% training sessions.

Time frame

Over intervention period (from randomization until time of transplantation, up to maximum of 24 months)

Adverse Events and IMT Training Side Effects Reported by Participants

Adverse events and training side-effects (e.g., muscle soreness) with inspiratory muscle training will be monitored through participant training diaries during the study intervention period. The research coordinator will review these diaries with participants on a weekly basis. Additionally, participants will be strongly encouraged to promptly inform the study team if they experience any challenges with IMT.

Time frame

Over intervention period (from randomization until time of transplantation, up to maximum of 24 months)

Secondary outcomes

Respiratory Muscle Endurance Test

Respiratory muscle endurance (measured in seconds) will be assessed at 30-50% of Maximum Inspiratory Pressure (MIP) using a manual threshold loading device (Powerbreathe Classic light resistance trainer)

Time frame

Change from baseline at 4 weeks, 8 weeks, 12 weeks, every 3 months until lung transplant (up to 24 months total), and 3 months post-transplant

Dyspnea Severity Assessed by Medical Research Council Dyspnea Scale

The Medical Research Council Dyspnea Scale will be used to assess the effect of breathlessness on daily activities. The scale comprises five statements that describe the range of respiratory dyspnea from none (Grade 1) to severe with difficulties performing self-care (Grade 5).

Time frame

Change from baseline at 4 weeks, 8 weeks, 12 weeks, every 3 months until lung transplant (up to 24 months total), and 3 months post-transplant

Qualitative Measures of Dyspnea Assessed by Qualitative Dyspnea Scale

The 18-point Qualitative Dyspnea Scale will be ascertained at each follow-up time point. Participants will be presented with a list of 18 qualitative descriptors of dyspnea experience and will be asked to rank their top three.

Time frame

Change from baseline at 4 weeks, 8 weeks, 12 weeks, every 3 months until lung transplant (up to 24 months total), and 3 months post-transplant

Mood Assessed by Depression, Anxiety, and Stress Scale

The Depression, Anxiety and Stress Scale (DASS-21) questionnaire has 21 items to assess mood (anxiety, depression, and stress). Each statement for the three domains is given a score of 0 (not applicable) to 3 (applicable most of the time) with scores categorized as follows: Normal, Mild, Moderate, Severe, and Extremely Severe.

Time frame

Change from baseline at 4 weeks, 8 weeks, 12 weeks, every 3 months until lung transplant (up to 24 months total), and 3 months post-transplant

Other outcomes

Diaphragm Thickness and Thickening Fraction Assessed by Ultrasound

The right hemi-diaphragm thickness and thickening fraction will be measured using a 13 Megahertz ultrasound transducer. Bright-mode (B-mode) ultrasound will be used to visualize the diaphragm and motion-mode (M-mode) will be utilized to assess the amplitude of the cranio-caudal diaphragmatic excursion during quiet and deep breathing. Diaphragm thickness will be measured in M-mode with a 5-13 MHz linear transducer over the apposition zone, near the costophrenic angle, from the most superficial hyperechoic line (pleural line) to the deepest hyperechoic line (peritoneal line).

Time frame

Change from baseline to all on-site visits at 4 weeks, 8 weeks, 12 weeks, every 3 months until lung transplant (up to 24 months total), time of liberation from MV, and 3 months post-transplant

Histopathology Analyses of Diaphragm Biopsies (Optional)

Participants will have the option of consenting to diaphragm biopsies collected during the transplant surgery. Biopsies (50 mg) will be procured from the anterolateral region of the right costal hemi-diaphragm midway between the origin and insertion. A portion of the tissue sample (20mg) will be fixed in formalin for histopathology analyses including assessing fibre type distribution, fibre type-specific cross-sectional area, immune infiltration, oxidative capacity, and fibrosis using light microscopy.

Time frame

At the time of lung transplantation, up to maximum of 24 months after randomization

Biochemical Analyses of Diaphragm Biopsies (Optional)

A second tissue portion (20mg) will be flash frozen in liquid nitrogen to assess mitochondrial content (via western blotting) and signaling cascades to examine atrophic signaling cascades using polymerase chain reactions.

Time frame

At the time of lung transplantation, up to maximum of 24 months after randomization

Mitochondrial Respirometry Analyses of Diaphragm Biopsies (Optional)

The final tissue portion (10 mg) will be used for live assessments of mitochondrial function using the Oroboros O2K High Resolution Respiratory system on the day of transplantation, as quickly after biopsy collection as possible.

Time frame

At the time of lung transplantation, up to maximum of 24 months after randomization

Sponsors and contacts

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University Health Network, Toronto

Lead sponsor

Canadian National Transplant Research Program

Collaborator

Canadian Institutes of Health Research (CIHR)

Collaborator

Ozmosis Research Inc.

Collaborator

Centre hospitalier de l'Université de Montréal (CHUM)

Collaborator

Vancouver General Hospital

Collaborator

Source ClinicalTrials.gov

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