Ignite Creation Date:
2025-12-24 @ 9:47 PM
Ignite Modification Date:
2026-01-01 @ 7:44 AM
Study NCT ID:
NCT06370832
Status:
RECRUITING
Last Update Posted:
2025-09-16
First Post:
2024-03-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Inspiratory Muscle Training in Lung Transplant Candidates
Sponsor:
University Health Network, Toronto
Organization:
Study Overview
Official Title:
Inspiratory Muscle Training in Lung Transplant Candidates and Implications on Early Post-Transplant Outcomes: A Pilot and Feasibility Multicenter Randomized Clinical Trial
Status:
RECRUITING
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: