Effect of Protein, Mobility Therapy and Electric Stimulation on Recovery in Older ICU Survivors

Study Overview
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Brief Summary
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Older ICU survivors with ICU acquired weakness (ICUAW) are malnourished, sarcopenic, and functionally debilitated as a consequence of the high burden of comorbidities common in the elderly. To address the sequalae of critical illnesses, the investigators will perform a trial incorporating an intervention that combines mobility-based physical rehabilitation (MRP), high protein supplementation (HPRO), and neuromuscular electric stimulation (NMES). The investigators will then assess both clinical and functional outcomes and determine the relationship of disability with systemic inflammation.

Detailed Description
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Annually, nearly 3 million patients ≥ 65 years old are admitted to intensive care units (ICUs) nationwide, 20% of whom experience a long, protracted ICU stay resulting in muscle deconditioning, atrophy, inflammation, and functional disability necessitating transfer from the ICU to a long term acute care hospitals (LTACH). In the LTACH exacerbations of chronic comorbidities and the cycle of prolonged bed rest, ongoing inflammation and malnutrition often leads to continued functional disability, immobility, prolonged mechanical ventilation and increased one-year mortality of up to 25%. After a patient has survived critical illness and is transferred to an LTACH facility, one of the major challenges of their continued care is how to address - and ameliorate - their profound physical and functional deficits. To address these sequalae of chronic critical illness, the investigators will perform a trial incorporating an intervention that combines mobility-based physical rehabilitation (MRP), high protein supplementation (HPRO) and neuromuscular electric stimulation (NMES) to assess both clinical and functional outcomes and to determine the relationship of disability with systemic inflammation. The investigators will prospectively randomize patient to receive our multicomponent intervention or usual care and assess the outcomes of functional mobility, change in muscle mass and discharge disposition. Additionally, the investigators will determine the effects of our intervention on inflammatory cytokine profiles to determine to what degree systemic inflammation mediates clinical recovery.

Official Title
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Effect of Protein, Mobility Therapy and Electric Stimulation on Recovery in Older Survivors of Critical Illness

Conditions
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Sarcopenia, Critical Illness, ICU Acquired Weakness

Intervention / Treatment
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* Combination Product: MRP and High Protein Supplement (HPRO) and Neuromuscular Electric Stimulation (NMES)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: LTACH admission within 72 hours Age ≥ 60 years old Prior ICU stay ≥ 2 weeks Able to follow commands in English Pre-ICU Barthel Index ≥ 70 Able to give consent Able to perform physical therapy All four limbs intact and mobile prior to LTACH admission Exclusion Criteria: Acute kidney injury with a glomerular filtration rate <15 ml/min Diagnosis of severe organ dysfunction including end stage liver disease or cirrhosis Diagnosis of active cancer Severe functional impairment or physical impairment to rehabilitation Liver function tests >2.5x normal limits Chronic dementia or cognitive impairment

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 99 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: UC only<br>LTACH control group receiving usual care (UC) only. | |
| Active Comparator: MRP+HPRO+NMES+UC<br>LTACH group receiving mobility based rehabilitation (MRP) + neuromuscular electric stimulation (NMES) + high protein supplementation (HPRO) + usual care (UC) | Combination Product: MRP and High Protein Supplement (HPRO) and Neuromuscular Electric Stimulation (NMES)<br>* Mobility-based physical rehabilitation sessions performed 5 times/week by a study PT to provide strength and cardiopulmonary endurance training. High whey protein shakes prescribed to a total intake of 1.6-1.8 g/kg/d in 2 divided doses based on caloric needs. 2 x 30-minute lower extremity electric stimulation sessions/day, 5 times/wk performed by study PT.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Muscle mass | Muscle mass will be measured by lower extremity muscle CT scans to calculate muscle volume and cross sectional area. | Days 0 to 14 to 28 | 
| Change in Muscle strength | Handgrip strength obtained using a hand grip dynamometer and manual muscle testing using hand held dynamometer | Days 0, 7, 14, 21 and 28 | 
| Change in Systemic Inflammation | Quantitative analysis of CRP, IFN-γ, IL-1α, IL-1β, IL-6, and IL-8. | Days 0, 7, 14, 21 and 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Functional status - SPPB | Functional status will be assessed by using the Short Physical Performance Battery (SPPB) | Days 0, 7, 14, 21 and 28 | 
| Change in Functional status - FSS-ICU | Functional status will be assessed by using the Functional Status Score in the ICU (FSS-ICU). | Days 0, 7, 14, 21 and 28 | 
| Change in Mobility status - ICU mobility Scale | Mobility status will be assessed weekly using the 1-item ICU Mobility Scale weekly in those physically capable. | Days 0, 7, 14, 21 and 28 | 
| Change in Mobility status - 6 minute walk distance | Mobility status will be assessed weekly using the total 6 Minute Walk distance in those physically capable. | Days 0, 7, 14, 21 and 28 | 
| Change in Mobility status - gait speed | Mobility status will be assessed weekly using gait speed in those physically capable. | Days 0, 7, 14, 21 and 28 | 
| Discharge disposition (LTACH to home, nursing home, acute rehabilitation, readmission, or death) | Discharge disposition from the LTACH to home, nursing home, acute rehabilitation, readmission, or death) | up to or after Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Long Term Acute Care Hospital, Protein, Neuromuscular electric stimulation, Physical Rehabilitation, Geriatric population, ICU Acquired Weakness, Critical Care