Progressive Rehabilitation Therapy in Patients With Advanced Lung Disease

Study Overview
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Brief Summary
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The International Society of Heart and Lung Transplantation Registry data shows that there is a growing population of critically ill patients with advanced lung disease undergoing lung transplantation. The goal of our study is to evaluate the role of intensive physical therapy for patients with advanced lung disease requiring transplant or ECMO(extracorporeal membrane oxygenation)- bridge to transplant with emphasis on the restoration of functional independence and prevention of functional declines after lung transplantation. The project is a designed as a randomized prospective research study investigating the impact of a multi-modal rehabilitation program(MRP), which incorporates neuromuscular electric stimulation(NMES), strength and mobility training, and nutritional supplementation(NS) in ameliorating the loss of muscle mass and strength, and lower extremity balance, strength and coordination that will decrease time on the ventilator or ECMO, stay in the ICU and hospital.

Detailed Description
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Intensive rehabilitation is recognized as an essential component to successful outcomes for post procedure recovery after a major cardio-thoracic procedure. The investigators propose a unique multi-modal rehabilitation program (MRP) that combines a step-up physical therapy protocol with neuromuscular electric stimulation (NMES), nutritional supplementation (NS), occupational therapy and pulmonary rehabilitation techniques to achieve improved functional outcomes for advanced lung disease patients requiring transplantation or ECMO-bridge to transplant. The investigators hypothesized that a progressive rehabilitation program, incorporating neuromuscular electric stimulation, strength and balance training, and nutritional supplementation with essential amino acids will reduce sarcopenia and loss of functional mobility in patients with advanced lung disease requiring transplantation or ECMO-bridge to transplant. The purpose of this study is to determine the effectiveness of a progressive rehabilitation program, which incorporates neuromuscular electric stimulation, strength and mobility training, and nutritional supplementation in ameliorating 1) the loss of muscle mass and strength, and lower extremity balance, strength and coordination, 2) time on the ventilator or ECMO, stay in the intense care unit and hospital, and 3) return home and quality of life compared to usual ICU care. The investigators propose a prospective, randomized interventional trial assessing the effectiveness of the program in decreasing adverse post-transplant outcomes compared to usual care. All advanced lung disease patients listed for transplantation or requiring ECMO cannulation will be screened for this study according to the inclusion and exclusion criterion. The patients will be randomized to either the treatment arm or usual care within 72 hours after the procedure (transplant or ECMO cannulation if patient requires ECMO-bridge to transplant). All groups of patients will undergo an initial global assessment of functional capabilities after listing for lung transplantation and then again within 72 hours after cardio-thoracic procedure (transplant or ECMO cannulation). Patients in the treatment arm will receive additional physical therapy that include: arm and leg exercises, using light weight machines, hand weights, or rubber bands, exercise machines such as portable arm or seated bikes. The treatment group will receive exercise therapy plus therapy with an electric stimulator device. This device uses weak electric impulses to involuntarily exercise the muscles (one-two sessions a day, with each session starting off at 10 minutes, then increasing to a maximum of 30 minutes). Subjects receiving the intervention will receive daily treatment using the neuromuscular electric stimulation unit. Four muscle groups (quadriceps and dorsiflexors bilaterally) will be stimulated using 3x5 inch surface electrodes (quadriceps) and 2x4 inch (dorsiflexors). In addition, patients in the experimental group will receive nutrition supplementation with essential amino acids 3 times a day in their feeding to prevent muscle breakdown and promote positive nitrogen balance. Comprehensive re-assessments are repeated on a weekly basis and the therapy will be adjusted to the patient's clinical status.

Official Title
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Assessing the Functional Impact of Progressive Rehabilitation Therapy in Patients With Advanced Lung Disease Requiring Lung Transplantation or ECMO- Bridge to Transplant

Conditions
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Advanced Lung Disease, Lung Transplant, Extracorporeal Membrane Oxygenation

Intervention / Treatment
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* Device: MRP and NMES(neuromuscular electric stimulation)
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced lung disease requiring lung transplantation Advanced lung disease requiring ECMO bridge to lung transplantation Patient or legally authorized representative are able to provide written or witnessed verbal consent. Exclusion Criteria: Unable to obtain consent from patient or family member Advanced lung disease but not transplant candidate due to other comorbidities Patient is deemed unsafe for rehabilitation by the transplant physician

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ECMO- Bridge to Transplant<br>Interventions: MRP+MNES(neuromuscular electric stimulation).Patients in the treatment arm will receive additional physical therapy(arm and leg exercises, using light weight machines, hand weights, or rubber bands, exercise machines such as portable arm or seated bikes) as well as therapy with an electric stimulator device. This device uses weak electric impulses to involuntarily exercise the muscles(one-two sessions a day).Four muscle groups(quadriceps and dorsiflexors bilaterally) will be stimulated using surface electrodes .In addition, patients in the experimental group will receive nutrition supplementation with essential amino acids 3 times a day in their feeding to prevent muscle breakdown and promote positive nitrogen balance. | Device: MRP and NMES(neuromuscular electric stimulation)<br>* nutrition supplementation includes addition of essential amino acids 3 times a day to feeding<br>* Other names: Dietary Supplement(NS);|
| Other: ECMO- Bridge to Transplant Control Group<br>Interventions: standard of care Patients are not going to receive any additional intervention. | Other: Standard of Care<br>* Patients in the control group are going to receive standard of care<br>|
| Active Comparator: Transplant<br>Interventions: MRP+MNES(neuromuscular electric stimulation).Patients in the treatment arm will receive additional physical therapy(arm and leg exercises, using light weight machines, hand weights, or rubber bands, exercise machines such as portable arm or seated bikes) as well as therapy with an electric stimulator device. This device uses weak electric impulses to involuntarily exercise the muscles(one-two sessions a day).Four muscle groups(quadriceps and dorsiflexors bilaterally) will be stimulated using surface electrodes .In addition, patients in the experimental group will receive nutrition supplementation with essential amino acids 3 times a day in their feeding to prevent muscle breakdown and promote positive nitrogen balance. | Device: MRP and NMES(neuromuscular electric stimulation)<br>* nutrition supplementation includes addition of essential amino acids 3 times a day to feeding<br>* Other names: Dietary Supplement(NS);|
| Other: Transplant Control Group<br>Interventions: standard of care. Patients are not going to receive any additional intervention. | Other: Standard of Care<br>* Patients in the control group are going to receive standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global muscle strength | Muscle group strength is obtained using hand held dynamometer | 14 days | 
| Mobility status | Mobility status is assessed with 6 minute walk distance | 14 days | 
| Muscle mass | Muscle mass measurement of lower extremity muscle volume using ultrasound scan or computer tomography | 14 days, | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time on the ventilator or ECMO | Measured as ECMO or ventilator days | 14 days, 1 month | 
| Stay in the ICU and hospital | Measured as days in the ICU and hospital | 14 days, 1,3month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transplant, ECMO, Sarcopenia, Deconditioning, Physical therapy