Inspiratory Muscle Training in Lung Transplant Candidates

NCT ID: NCT06370832

Last Updated: 2025-09-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-06
• Study Completion Date: 2027-09-30

Brief Summary

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).

Detailed Description

Diaphragm atrophy at the time of initiating mechanical ventilation (MV) after solid organ transplantation and major surgery is associated with prolonged MV and higher hospital mortality. The incidence of diaphragm dysfunction after LTx is estimated to be up to 30%; post-transplant diaphragm dysfunction is associated with prolonged MV and hospitalization after LTx.

The American Thoracic Society/European Respiratory Society (2013) guidelines recommend further evaluation of inspiratory muscle training (IMT) combined with routine rehabilitation prior to major surgery. Pre-operative IMT in patients with even normal maximal inspiratory pressures (MIP) have been shown to decrease post-operative pulmonary complications and shorten hospitalization after cardio-thoracic surgery. However, pre-operative IMT is not commonly used for LTx candidates and its benefits are poorly researched. IMT may prove to be a simple pre-transplant intervention to prevent post-transplant morbidity and improve post-transplant functional status. The current focus is to investigate the impact of IMT on early post-lung transplant results while evaluating its effectiveness through a pilot multicenter randomized controlled trial.

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.

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).

Hypotheses: 1) It will be feasible to recruit LTx candidates into an IMT program RCT with a consent rate ≥ 30 %, enrolment rate of 2-3 patients per month at UHN and 1 patient per month at each other participating site, adequate outcome ascertainment (≥ 80%), and acceptable adherence (≥ 80% compliance with IMT sessions). 2) IMT will increase respiratory muscle endurance by 20% and improve exertional dyspnea and HRQoL in comparison to usual care over the pre-transplant period. IMT will be associated with greater hospital free days at 90 days. 3) pre-transplant IMT increases diaphragm myofibrillar CSA and post-LTx diaphragm thickness and maximal diaphragm thickening during inspiration in comparison to usual care. The improved mitochondrial respiration will occur concurrently with improvements in muscle fiber size, immune infiltration and oxidative stress.

The IMT and exercise training group (IMT group) will perform two daily IMT sessions of 30 breaths (< 5 minutes/session) during the pre-LTx period. IMT will start at 30% of MIP with a 5-10% weekly increase in training intensity guided by weekly MIP as tolerated (median weekly Borg dyspnea score < 7 during IMT until reaching 70% of MIP) and continued until LTx. In conjunction with their IMT program, IMT group participants will undergo exercise training at least three times per week as part of their usual care. The control group (exercise training group) will perform exercise training as part of their usual care three times per week for the duration of the waitlist period. The exercise regimen for both groups consists of aerobic, resistance, and flexibility training supervised by a physiotherapist approximately three times a week. The training includes a combination of in-person visits and home-based sessions. Both groups will also receive a respiratory endurance device to evaluate respiratory endurance throughout the trial.

IMT can improve respiratory muscle strength and endurance, potentially helping those who are candidates for LTx. In addition, studying patients undergoing LTx affords unique opportunities to investigate the mechanistic effects of IMT on diaphragm structure and function.

Conditions

Inspiratory Muscle Training

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

IMT and exercise training group

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 Type: EXPERIMENTAL

IMT and exercise training group

Intervention Type: OTHER

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.

Usual care group

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

IMT and exercise training group

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)
• Present ruptures of eardrums or infections leading to fluid behind ear drum
• Marked left or right ventricular end-diastolic volume and pressure overload on right heart catheterization or echocardiogram
• Severe osteoporosis with history of rib fractures
• Cardiac pacemaker or other electronic or magnetic body implant
• Individuals listed as rapidly deteriorating or inpatient at the time of eligibility assessment
• Individuals awaiting a re-transplant
• Inability of the patient to connect to the internet

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian National Transplant Research Program

OTHER

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Ozmosis Research Inc.

INDUSTRY

Sponsor Role: collaborator

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: collaborator

Vancouver General Hospital

OTHER

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dmitry Rozenberg, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Health Network/University of Toronto

Locations

Vancouver General Hospital

Vancouver, British Columbia, Canada

Site Status: RECRUITING

University Health Network

Toronto, Ontario, Canada

Site Status: RECRUITING

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Dmitry Rozenberg, MD, PhD

Role: CONTACT

Dmitry.Rozenberg@uhn.ca

416-340-4800 ext. 7358

Facility Contacts

Jordan Guenette, PhD

Role: primary

Jordan.Guenette@hli.ubc.ca

604-806-8835

Dmitry Rozenberg, MD, PhD

Role: primary

dmitry.rozenberg@uhn.ca

416-340-4800 ext. 7358

Tania Janaudis-Ferreira, PhD

Role: primary

tania.janaudis-ferreira@mcgill.ca

514-619-0871

References

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Reference Type: BACKGROUND

PMID: 25085497 (View on PubMed)

Hook JL, Lederer DJ. Selecting lung transplant candidates: where do current guidelines fall short? Expert Rev Respir Med. 2012 Feb;6(1):51-61. doi: 10.1586/ers.11.83.

Reference Type: BACKGROUND

PMID: 22283579 (View on PubMed)

Fuehner T, Kuehn C, Welte T, Gottlieb J. ICU Care Before and After Lung Transplantation. Chest. 2016 Aug;150(2):442-50. doi: 10.1016/j.chest.2016.02.656. Epub 2016 Mar 4.

Reference Type: BACKGROUND

PMID: 26953218 (View on PubMed)

Christie JD, Kotloff RM, Ahya VN, Tino G, Pochettino A, Gaughan C, DeMissie E, Kimmel SE. The effect of primary graft dysfunction on survival after lung transplantation. Am J Respir Crit Care Med. 2005 Jun 1;171(11):1312-6. doi: 10.1164/rccm.200409-1243OC. Epub 2005 Mar 11.

Reference Type: BACKGROUND

PMID: 15764726 (View on PubMed)

Adler D, Dupuis-Lozeron E, Richard JC, Janssens JP, Brochard L. Does inspiratory muscle dysfunction predict readmission after intensive care unit discharge? Am J Respir Crit Care Med. 2014 Aug 1;190(3):347-50. doi: 10.1164/rccm.201404-0655LE. No abstract available.

Reference Type: BACKGROUND

PMID: 25084264 (View on PubMed)

Sklar MC, Dres M, Fan E, Rubenfeld GD, Scales DC, Herridge MS, Rittayamai N, Harhay MO, Reid WD, Tomlinson G, Rozenberg D, McClelland W, Riegler S, Slutsky AS, Brochard L, Ferguson ND, Goligher EC. Association of Low Baseline Diaphragm Muscle Mass With Prolonged Mechanical Ventilation and Mortality Among Critically Ill Adults. JAMA Netw Open. 2020 Feb 5;3(2):e1921520. doi: 10.1001/jamanetworkopen.2019.21520.

Reference Type: BACKGROUND

PMID: 32074293 (View on PubMed)

Other Identifiers

22-5171

Identifier Type: -

Identifier Source: org_study_id