The Effect of High Protein and Early Resistance Exercise Versus Usual Care in Critically Ill Patients

Study Overview
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Brief Summary
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This is a 2-arm, parallel-group, randomized controlled trial that investigates the effect of combined high protein and early resistance exercise versus usual care on muscle mass, quality and strength, clinical outcomes, functional outcomes and quality of life in mechanically ventilated critically ill patients

Detailed Description
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With the advancement of critical care, about 80% of ICU patients are surviving critical illness. However, ICU survivors often experience significant post-ICU morbidities including muscle weakness and impairments in physical functioning that can persist for years. We hypothesized that early intervention with two of the most basic features of critical care: nutrition (feeding high protein) together with mobility (early resistance exercise) may help to attenuate muscle loss, thereby reducing the severity of ICU-acquired weakness and its associated physical impairments. A 2-arm, parallel-group, randomized controlled trial is proposed to investigate the effect of the combined interventions. The intervention will be conducted for up to 28 days in the ICU. Outcome measurements will be conducted by a blinded assessor at baseline (within 24 hours of randomization), Day 10 post-randomization, before hospital discharge and at 6-month post-randomization. Ultrasound and bioelectrical impedance analysis will be conducted to measure muscle mass and quality. Manual muscle testing, handgrip and knee extension strength will also be measured. Physical function will be assessed by a series of test including the six minutes walk test. Telephone interview will be conducted to administer quality of life questionnaires at 6 months. These combined simple and non-invasive interventions, if proven effective, may potentially revolutionize critical care.

Official Title
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The Effect of High Protein and Early Resistance Exercise Versus Usual Care on Muscle Mass, Strength and Quality, Clinical Outcomes, Functional Outcomes and Quality of Life in Mechanically Ventilated Critically Ill Patients

Conditions
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Critical Illness

Intervention / Treatment
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* Other: High protein and early exercise
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years old and above Mechanically ventilated and expected to remain mechanically ventilated for an additional 48 hours from screening High nutritional risk (at least one of the following): BMI ≤ 25 or ≥ 35 Moderate to severe malnutrition as defined by Subjective Global Assessment (SGA) Frailty (Clinical Frailty Scale ≥ 5 from proxy) SARC-F (note: 'sarc-f' is the full name, not an abbreviation) questionnaire ≥ 4 From point of screening, projected duration of mechanical ventilation of >4 days Exclusion Criteria: >96 continuous hours of mechanical ventilation before screening Expected death or withdrawal of life-sustaining treatments within 7 days from screening Pregnant (Note: post-partum and lactating patients are not excluded from the trial) The responsible clinician feels that the patient either needs low or high protein Patient requires parenteral nutrition only and site does not have products to reach the high protein dose group. Not ambulating independently prior to illness that lead to ICU admission (use of gait aid permitted) Lower extremity injury or impairments that prevents them walking prior to hospital discharge (e.g. amputation, knee/hip injury) Pre-existing cognitive impairment or language barrier that prohibits outcomes assessment Pre-existing primary severe systemic neuromuscular disease resulting in severe weakness pre-ICU (e.g., Guillain Barre) Intracranial or spinal process affecting motor function Patients in hospital >5 days prior to ICU admission Not expected to stay ≥4 days after enrollment Neuromuscular blocker infusion (eligible once infusion discontinued if other inclusion criteria met) Lower extremity injury or impairments that prevents cycling (e.g. amputation, knee/hip injury) Weight ≥150 kg Physician declines enrolment for Exercise

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Protein and Early Exercise<br>High protein is defined as a protein prescription of ≥2.2 gram/kg body weight; Early exercise is defined as exercise by using cycle ergometry for 45 minutes per day within 24 hours of randomization | Other: High protein and early exercise<br>* High protein is defined as protein prescription of ≥2.2 gram/kg body weight and early exercise is defined as starting cycle ergometry intervention within 24 hours of randomization<br>|
| Active Comparator: Usual Care<br>Usual care has a protein prescription of ≤1.2 gram/kg body weight and exercise prescription as per the discretion of attending clinicians | Other: Usual Care<br>* Usual care group has protein prescription of ≤1.2 gram/kg body weight and exercise at the discretion of attending clinicians<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rectus femoris cross-sectional area (RFCSA) | RFCSA measured by ultrasonography | Change in RFCSA between Day 1 and Day 10 of randomization | 
| Rectus femoris cross-sectional area (RFCSA) | RFCSA measured by ultrasonography | Change in RFCSA between Day 1 of randomization and within 72 hours before discharge from the hospital | 
| Rectus femoris linear depth (RF LD) | RF LD measured by ultrasonography | Change in RF LD between Day 1 and Day 10 of randomization | 
| Rectus femoris linear depth (RF LD) | RF LD measured by ultrasonography | Change in RF LD between Day 1 of randomization and within 72 hours before discharge from the hospital | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quadriceps muscle echogenicity | Quadriceps muscle echogenicity measured by ultrasonography | Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital | 
| Quadriceps muscle pennation angle | Quadriceps muscle pennation angle measured by ultrasonography | Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital | 
| Quadriceps muscle fascicle length | Quadriceps muscle fascicle length measured by ultrasonography | Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital | 
| Functional Status Score for the Intensive Care Unit (FSS-ICU) | An assessment that consist of rolling, transfer from supine to sit, sitting at the edge of bed, transfer from sit to stand and walking | Day 1 of randomization (surrogate interview), within 72 hours before discharge from the ICU and hospital (by trained physiotherapist) | 
| Short Physical Performance Batteries (SPPB) | An assessment that consist of balance test, gait speed test and chair stand test | Within 72 hours before discharge from the ICU and hospital | 
| Handgrip strength | Handgrip strength of both hands by using handgrip dynamometer | Within 72 hours before discharge from the ICU and hospital | 
| 6 minutes walk test | To evaluate how far the subject can walk in 6 minutes time | Within 72 hours before discharge from the hospital | 
| Manual muscle testing | Bilateral muscle strength for shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension and ankle dorsiflexion | Within 72 hours before discharge from the hospital | 
| Knee extension strength | Knee extension strength measured by Handheld Dynamometer | Within 72 hours before discharge from the hospital | 
| Mortality | Percentage of patient who died | Percentage of Patient who died within this ICU or hospital admission, at day 60 and 6 months post-randomization | 
| Time-to-discharge alive from the hospital | Time-to-discharge alive from the hospital | Time elapsed from randomization to hospital discharge (for a maximum of 6 months from randomization) | 
| Length of mechanical ventilation | Duration of mechanical ventilation | Total time from start to end of mechanical ventilation for a maximum of 6 months from randomization | 
| Health-related Quality of life by 36-item short form survey (SF-36) | SF-36 is a questionnaire that will be administered by telephone interview | 6 months after randomization | 
| Health-related Quality of life by Euro Quality of Life 5 Dimension 5 level (EQ-5D-5L) | EQ-5D-5L is a questionnaire that will be administered by telephone interview | 6 months after randomization | 
| Katz Activities of Daily Living (ADL) | Katz ADL is a questionnaire that will be administered by either surrogate or telephone interview | Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview) | 
| Lawton Instrumental Activities of Daily Living (IADL) | Lawton IADL is a questionnaire that will be administered by either surrogate or telephone interview | Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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protein, exercise, muscle