Inspiratory Muscle Training for Lung Transplant Candidates

Recruiting at 2 trial locations

Overseen By Dmitry Rozenberg, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Respiratory exacerbation, Neurologic conditions, Pneumothorax, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Inspiratory Muscle Training for lung transplant candidates?

Inspiratory muscle training (IMT) has shown potential benefits in improving exercise capacity and breathing difficulties in lung transplant candidates, as well as in people with chronic lung conditions like COPD. Studies suggest it can strengthen breathing muscles, which might help patients prepare for lung transplants. ^{1 2 3 4 5}

Is inspiratory muscle training safe for humans?

Inspiratory muscle training (IMT) has been used safely in both healthy individuals and those with various health conditions, including patients in intensive care. Studies have shown it is generally well-tolerated and considered safe. ^{1 2 6 7 8}

How is inspiratory muscle training different from other treatments for lung transplant candidates?

Inspiratory muscle training (IMT) is unique because it specifically targets and strengthens the muscles used for breathing, which can improve respiratory muscle strength and endurance. Unlike other treatments, it involves exercises using devices to provide resistance, helping to enhance lung function and overall respiratory health, especially beneficial for those with weakened respiratory muscles. ^{1 2 6 7 8}

What is the purpose of 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).

Research Team

Dmitry Rozenberg, MD, PhD

Principal Investigator

University Health Network/University of Toronto

Eligibility Criteria

This trial is for adults over 18 awaiting lung transplants due to Interstitial Lung Disease or Chronic Obstructive Pulmonary Disease, who are already in outpatient pulmonary rehab. It's not for those with recent pneumothorax, severe heart issues, pacemakers, re-transplant candidates, internet access issues, recent respiratory flare-ups, ear problems that affect pressure regulation, severe osteoporosis with rib fractures history or certain neurological/musculoskeletal conditions.

Inclusion Criteria

Lung Transplant Candidates

I have been diagnosed with ILD or COPD.

I am currently in an outpatient lung rehab program.

Exclusion Criteria

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

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

Marked left or right ventricular end-diastolic volume and pressure overload on right heart catheterization or echocardiogram

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Transplant Inspiratory Muscle Training

Participants perform inspiratory muscle training (IMT) and exercise training sessions during the pre-lung transplant phase.

Up to 24 months

Weekly in-person and home-based sessions

Post-Transplant Follow-up

Participants are monitored for safety and effectiveness after lung transplant, including assessments of respiratory muscle endurance and health-related quality of life.

3 months

Regular follow-up visits

Long-term Follow-up

Participants continue to be monitored for long-term outcomes and post-transplant recovery.

Up to 24 months

Treatment Details

Interventions

• Inspiratory Muscle Training

Trial Overview The study tests if Inspiratory Muscle Training (IMT) can improve breathing muscle strength before a lung transplant and help patients recover faster post-surgery. Participants will be randomly assigned to either an IMT program or usual care and tracked through various health assessments up until three months after their transplant.

Participant Groups

Group I: IMT and exercise training group Experimental Treatment 1 Intervention

Participants in the IMT and exercise training group will perform twice daily 30-breath IMT sessions and exercise training sessions three times per week as part of their usual care during the pre-lung transplant phase. The exercise training is comprised of aerobic, resistance and flexibility training.

Group II: Usual care group Active Control 1 Intervention

Participants in the usual care group will take part in the standard of care rehabilitation program provided during the waitlist phase prior to the transplant. Exercise training is performed at least three times per week for the duration of the waitlist period. The exercise training includes a combination of supervised in-person visits and home-based training that incorporates aerobic, resistance and flexibility training.

Inspiratory Muscle Training is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Inspiratory Muscle Training for:

• Chronic Obstructive Pulmonary Disease (COPD)
• Congestive Heart Failure
• Spinal Cord Injury
• Multiple Sclerosis

Approved in United States as Inspiratory Muscle Training for:

• Chronic Obstructive Pulmonary Disease (COPD)
• Congestive Heart Failure
• Spinal Cord Injury
• Multiple Sclerosis
• Cardiac Rehabilitation

Approved in Canada as Inspiratory Muscle Training for:

• Chronic Obstructive Pulmonary Disease (COPD)
• Congestive Heart Failure
• Spinal Cord Injury
• Multiple Sclerosis

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Canadian National Transplant Research Program

Collaborator

Trials

9

Recruited

1,600+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Ozmosis Research Inc.

Industry Sponsor

Trials

25

Recruited

5,200+

Centre hospitalier de l'Université de Montréal (CHUM)

Collaborator

Trials

389

Recruited

143,000+

Vancouver General Hospital

Collaborator

Trials

42

Recruited

19,700+

Findings from Research

Inspiratory muscle training (IMT) improves the strength and endurance of inspiratory muscles, reduces dyspnoea during daily activities, and enhances quality of life, but does not offer additional benefits when combined with standard pulmonary rehabilitation programs.

IMT is beneficial for patients who cannot engage in full exercise training, and it shows promise in pre-operative programs, suggesting it may be a useful intervention in specific contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Inspiratory muscle training during pulmonary rehabilitation]. Beaumont, M., Le Tallec, F., Villiot-Danger, E.[2021]

Inspiratory muscle training (IMT) combined with pulmonary rehabilitation (PR) did not show significant improvements in dyspnea, functional exercise capacity, or health-related quality of life in COPD patients, based on a review of 55 randomized controlled trials involving 4,467 participants.

However, IMT alone may lead to better outcomes in these areas, suggesting that while IMT can be beneficial, its effectiveness may be diminished when combined with PR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inspiratory muscle training, with or without concomitant pulmonary rehabilitation, for chronic obstructive pulmonary disease (COPD). Ammous, O., Feki, W., Lotfi, T., et al.[2023]

In a study of 34 lung transplantation candidates, those who received inspiratory muscle training (IMT) alongside pulmonary rehabilitation showed a significant improvement in exercise capacity, walking an additional 100 meters compared to those who only underwent pulmonary rehabilitation.

The IMT group also experienced a notable increase in maximum inspiratory pressure and carbon monoxide diffusion capacity, indicating enhanced respiratory function, while both groups reported reduced dyspnea scores, although the difference between groups was not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of inspiratory muscle training on exercise capacity, dyspnea and respiratory functions in lung transplantation candidates: a randomized controlled trial. Pehlivan, E., Mutluay, F., Balcı, A., et al.[2019]

The new inspiratory muscle training and positive expiratory pressure (IMT/PEP) device improved maximal expiratory pressure in older men and showed non-inferiority compared to the Threshold IMT device, confirming its efficacy for respiratory muscle training.

Both home-based and center-based training protocols had high adherence rates (91-99%), suggesting that with proper education, home-based training can be effective for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a new respiratory muscle training device in community-dwelling elderly men: an open-label, randomized, non-inferiority trial. Kim, SH., Shin, MJ., Lee, JM., et al.[2022]

Respiratory muscle training (RMT) significantly improved inspiratory muscle strength in patients with restrictive thoracic disorders, with a 27.6% increase in maximal inspiratory mouth pressure after three months of training.

Patients who underwent RMT also showed enhanced exercise performance and health-related quality of life, evidenced by increased peak oxygen consumption and improved physical performance scores compared to the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory muscle training in restrictive thoracic disease: a randomized controlled trial. Budweiser, S., Moertl, M., Jörres, RA., et al.[2006]

High-intensity inspiratory muscle training (IMT) at 80% of maximal effort significantly improved inspiratory muscle function, lung volumes, work capacity, and power output in healthy individuals, based on a study involving 40 participants over 8 weeks.

IMT at 60% of maximal effort also enhanced work capacity and power output, but lower intensities (40%) did not yield any measurable improvements, indicating that higher training intensities are crucial for achieving functional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of inspiratory muscle training intensities on pulmonary function and work capacity in people who are healthy: a randomized controlled trial. Enright, SJ., Unnithan, VB.[2011]

Inspiratory muscle training (IMT) significantly improves balance in both healthy and diseased adults, based on a systematic review of 10 randomized control trials.

The effects of IMT on functional mobility were inconclusive, indicating that while balance benefits are clear, more research is needed to understand its impact on overall mobility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of inspiratory muscle training on balance and functional mobility: a systematic review. Sheraz, S., Ferraro, FV., Siddiqui, FA., et al.[2023]

A study involving 40 critically ill patients showed that using an electronic device for inspiratory muscle training (IMT) was feasible, with 81% of planned sessions completed, indicating good adherence to the intervention.

The electronic IMT was found to be safe, with no major adverse events and only 10% minor adverse events that were transient and without clinical consequences, while over 85% of participants reported it as helpful for their recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, safety, and patient acceptability of electronic inspiratory muscle training in patients who require prolonged mechanical ventilation in the intensive care unit: A dual-centre observational study. Nickels, M., Erwin, K., McMurray, G., et al.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

[Inspiratory muscle training during pulmonary rehabilitation]. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Inspiratory muscle training, with or without concomitant pulmonary rehabilitation, for chronic obstructive pulmonary disease (COPD). [2023]

3. England pubmed.ncbi.nlm.nih.gov

The effects of inspiratory muscle training on exercise capacity, dyspnea and respiratory functions in lung transplantation candidates: a randomized controlled trial. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Effects of a new respiratory muscle training device in community-dwelling elderly men: an open-label, randomized, non-inferiority trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Respiratory muscle training in restrictive thoracic disease: a randomized controlled trial. [2006]

6. United States pubmed.ncbi.nlm.nih.gov

Effect of inspiratory muscle training intensities on pulmonary function and work capacity in people who are healthy: a randomized controlled trial. [2011]

7. England pubmed.ncbi.nlm.nih.gov

The effects of inspiratory muscle training on balance and functional mobility: a systematic review. [2023]

8. Australia pubmed.ncbi.nlm.nih.gov

Feasibility, safety, and patient acceptability of electronic inspiratory muscle training in patients who require prolonged mechanical ventilation in the intensive care unit: A dual-centre observational study. [2023]