Effects of Early Exercise Rehabilitation in Severe Burns

Study Overview
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Brief Summary
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BACKGROUND: Postburn changes in glucose and protein metabolism are at their peak during the acute phase of severe burns. The resulting metabolic derangements lead to substantial muscle wasting, insulin resistance, which ultimately hampers full recovery and reintegration into society. PURPOSE: This randomized controlled trial was initiated to investigate the effects of exercise-based rehabilitation on muscle wasting, insulin resistance, and quality of life during the acute phase of severe adult burns. METHODS: Severly burned adults (40-80%TBSA) will be recruited from one of China's largest burn centres. Subjects allocated to the intervention group will undergo a 6-12 week long exercise program in addition to standard care rehabilitation. As part of the exercise program, participants will carry out progressive resistance and aerobic training, initiated as soon as medical safety and patient cooperation allow. Exercise type and dosage will be chosen according to patient status in terms of grafts, mobility, and strength. The control group will receive standard care rehabilitation only, including passive, assisted, active range of motion exercise, functional exercise, and scar treatment. The results of this translational research will provide insight into the effects and mechanisms of exercise on both a fundamental and clinical spectrum.

Detailed Description
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The added exercise intervention is initiated in line with the following readiness criteria, which were checked prior to each training session: Criteria: Cardiorespiratory stability: Mean arterial pressure (MAP) 60 - 110 mmHg fraction of inspired oxygen (FiO2) <60% partial pressure of oxygen / fraction of inspired oxygen (PaO2/FiO2) >200 Respiratory rate <40 bpm Positive end expiratory pressure (PEEP) <10 cmH2O no high inotropic doses (Dopamine >10 mcg/kg/min or Nor/adrenaline <0,1 mcg/kg/min) Temp. 36 - 38,5°C Richmond Agitation Sedation Scale (RASS) -2 - +2 Medical Doctor clearance Medical research council (MRC) score lower limbs ≥3 Accordingly, the post burn starting time differs per enrolled subject. Exercises are administered as in-bed exercises or out-of-bed exercises, depending on whether subjects are able and allowed to engage in out-of-bed mobility. Exercise intensity for resistance training is set at 60% peak force based on a weekly peak force measurement by hand-held dynamometry, or on a 3 RM in case of out of bed exercises. Aerobic exercise intensity is set at 50-75% peak Watts determined by a weekly cycle ergometer or treadmill ramp protocol.

Official Title
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Pathophysiological Mechanisms and Early Exercise Rehabilitation Counter Measures of Hypermetabolism and Muscle Wasting in Severe Burns.

Conditions
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Burns

Intervention / Treatment
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* Other: Exercise
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥40 - ≤70 %TBSA Burn depth: 2nd deep / 3rd degree Exclusion Criteria: Electrical burn (except flash burns) Associated injury: fracture lower limb Diabetes Mellitus type 1 Central neurological/neuromuscular disorders (interfering with assessment/exercise) Cognitive / psychological disorders (interfering with cooperation) Cardiopulmonary disease (interfering with exercise safety) Pregnancy Palliative care

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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
Interventional Model Description: Randomized Controlled Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care<br>Standard of care treatment: - including passive / assisted / active movements, stretching, functional exercise, scar treatment Duration: 6-12 weeks | Other: Standard of Care<br>* Standard of care rehabilitation<br>|
| Experimental: Exercise<br>Standard of care + added exercises Exercise type: resistance and aerobic exercise Resistance Exercise: 3x / week (manual resistance, free weights, machines) Aerobic exercise: 2x / week (cycle ergometer, treadmill) Duration: 6-12 weeks | Other: Exercise<br>* Resistance and aerobic exercise in addition to standard of care rehabilitation<br>Other: Standard of Care<br>* Standard of care rehabilitation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quadriceps muscle layer thickness (QMLT) | Method: B-mode ultrasound on the anterior aspect of the thigh. Technique: maximal and minimal pressure Location: measured at 1/2 and 2/3 of the distance between anterior superior iliac spine and the superior pole of the patella. Analysis: An average of 3 trials will be recorded and analyzed using dedicated software | Baseline - 12 weeks | 
| Change in rectus femoris cross sectional area (RF-CSA) | Method: B-mode ultrasound on the anterior aspect of the thigh. Technique: minimal pressure. Location: measured at the most proximal distance where the entire muscle belly is still visible on the ultrasound image. Analysis: An average of 3 trials will be recorded and analyzed using dedicated software. | Baseline - 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin resistance | Method: HOMA-2 calculated by fasting plasma glucose and insulin, analysed by Western Blot Chemiluminescence | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Burns, Exercise rehabilitation, Exercise Therapy, Muscle wasting, Hypermetabolism, Insulin resistance