Inspiratory Muscle Training in Lung Transplant Candidates

NCT06370832 | Recruiting DMC

• 1 other identifier: 22-5171
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 4

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).

Conditions

Inspiratory Muscle Training

Keywords

Lung transplant candidates; Exercise training; Prehabilitation; Chronic Obstructive Pulmonary Disease; Interstitial Lung Disease

Outcome Measures

Primary Outcomes (5)

• Study Recruitment According to Research Team Records

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

  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.

  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.

  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.

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

• Inspiratory Muscle Training Satisfaction Questionnaire (IMT Group Only)

  Participant satisfaction and motivation with the IMT intervention will be determined using a satisfaction questionnaire.

  At 3 months post-transplant follow-up

Secondary Outcomes (19)

• Respiratory Muscle Endurance Test

  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

  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

  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

  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

• Health-Related Quality of Life Assessed by St. George's Respiratory Questionnaire

  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 (4)

• Diaphragm Thickness and Thickening Fraction Assessed by Ultrasound

  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)

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

• Biochemical Analyses of Diaphragm Biopsies (Optional)

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

Study Arms (2)

IMT and exercise training group

EXPERIMENTAL

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.

Other: IMT and exercise training group

Usual care group

NO 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.

Interventions

IMT and exercise training group 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.

IMT and exercise training group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Ozmosis Research Inc.: collaborator
• Canadian National Transplant Research Program: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• Centre hospitalier de l'Université de Montréal (CHUM): collaborator
• Vancouver General Hospital: collaborator

Study Sites (4)

Edmonton Lung Transplant Program

Edmonton, Alberta, T6G 2G3, Canada

RECRUITING

Vancouver General Hospital

Vancouver, British Columbia, Canada

RECRUITING

University Health Network

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

RECRUITING

Related Publications (6)

• Weill D, Benden C, Corris PA, Dark JH, Davis RD, Keshavjee S, Lederer DJ, Mulligan MJ, Patterson GA, Singer LG, Snell GI, Verleden GM, Zamora MR, Glanville AR. A consensus document for the selection of lung transplant candidates: 2014--an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2015 Jan;34(1):1-15. doi: 10.1016/j.healun.2014.06.014. Epub 2014 Jun 26.

  PMID: 25085497 BACKGROUND

• 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.

  PMID: 22283579 BACKGROUND

• 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.

  PMID: 26953218 BACKGROUND

• 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.

  PMID: 15764726 BACKGROUND

• 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.

  PMID: 25084264 BACKGROUND

• 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.

  PMID: 32074293 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Lung Diseases, Interstitial

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dmitry Rozenberg, MD, PhD

  University Health Network/University of Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dmitry Rozenberg, MD, PhD

CONTACT

416-340-4800; Dmitry.Rozenberg@uhn.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Ascertainment of post-transplant clinical outcomes (including histopathology assessments) will be blinded by assessors to study group up to 3 months post-transplant.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pre-lung transplant candidates will be randomized to one of two groups: (1) IMT + exercise training; or (2) exercise training alone.

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: April 17, 2024
• Study Start: August 6, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: March 30, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)