Effects of Early Exercise Rehabilitation in Severe Burns

• ClinicalTrials.gov Identifier: NCT04372550
• Recruitment Status: Unknown
• First Posted: May 4, 2020
• Last Update Posted: August 12, 2020
• Sponsor: Universiteit Antwerpen
• Collaborators: Research Foundation Flanders; Wuhan Third Hospital
• Information provided by (Responsible Party): Ulrike Van Daele, Universiteit Antwerpen

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Burns	Other: Exercise; Other: Standard of Care	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized Controlled Trial
• Masking: None (Open Label)
• Masking Description: Analysis of the primary outcome is carried out blind.
• Primary Purpose: Treatment
• Official Title: Pathophysiological Mechanisms and Early Exercise Rehabilitation Counter Measures of Hypermetabolism and Muscle Wasting in Severe Burns.
• Actual Study Start Date: November 25, 2019
• Estimated Primary Completion Date: October 2021
• Estimated Study Completion Date: October 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Standard of Care; Standard of care treatment: - including passive / assisted / active movements, stretching, functional exercise, scar treatment Duration: 6-12 weeks	Other: Standard of Care; Standard of care rehabilitation
Experimental: Exercise; 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; Resistance and aerobic exercise in addition to standard of care rehabilitation; Other: Standard of Care; Standard of care rehabilitation

Outcome Measures

Primary Outcome Measures :

1. Change in quadriceps muscle layer thickness (QMLT) [ Time Frame: Baseline - 12 weeks ]

   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

2. Change in rectus femoris cross sectional area (RF-CSA) [ Time Frame: Baseline - 12 weeks ]

   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.

Secondary Outcome Measures :

1. Change in insulin resistance [ Time Frame: Baseline and 12 weeks ]
   Method: HOMA-2 calculated by fasting plasma glucose and insulin, analysed by Western Blot Chemiluminescence

Other Outcome Measures:

1. Change in Interleukin-1 [ Time Frame: Baseline and 12 weeks ]
   Western Blot Chemiluminescence
2. Change in Interleukin-6 [ Time Frame: Baseline and 12 weeks ]
   Western Blot Chemiluminescence
3. Change in Tumor Necrosis Factor alpha (TNF-α) [ Time Frame: Baseline and 12 weeks ]
   Western Blot Chemiluminescence
4. Change in C-reactive protein [ Time Frame: Baseline and 12 weeks ]
   Western Blot Chemiluminescence
5. Change in Insulin like growth factor 1 (IGF-1) [ Time Frame: Baseline and 12 weeks ]
   Western Blot Chemiluminescence
6. Change in Glucagon [ Time Frame: Baseline and 12 weeks ]
   ELISA kits DGCG0, R&D Systems, Inc, USA
7. Change in Myostatin [ Time Frame: Baseline and 12 weeks ]
   ELISA kits DGDF80, R&D Systems, Inc, USA
8. Change in isometric peak force (knee extension) [ Time Frame: Baseline and 12 weeks ]

   Method: Hand-held dynamometry (Lafayette instrument Co. Europe, U.K.). Isometric peak fore is measured by a 'make' manoeuvre with a fixation band disallowing movement.

   Test position: Supine with a fixation band fixed to the hospital bed. Analysis: Best of 3 trials

9. Change in isometric peak force (hip flexion) [ Time Frame: Baseline and 12 weeks ]

   Method: Hand-held dynamometry (Lafayette instrument Co. Europe, U.K.). Isometric peak fore is measured by a 'make' manoeuvre with a fixation band disallowing movement.

   Test position: Supine with a fixation band fixed to the hospital bed. Analysis: Best of 3 trials

10. Change in isometric peak force (hip extension) [ Time Frame: Baseline and 12 weeks ]

    Method: Hand-held dynamometry (Lafayette instrument Co. Europe, U.K.). Isometric peak fore is measured by a 'make' manoeuvre with a fixation band disallowing movement.

    Test position: Supine with a fixation band fixed to the hospital bed. Analysis: Best of 3 trials

11. Change in hand grip strength [ Time Frame: Baseline and 12 weeks ]
    Method: Baseline LITE hydraulic dynamometer Analysis: Best of 3 trials
12. Change in Burn Specific Health Scale-Brief (BSHS-B) [ Time Frame: Baseline and 12 weeks ]

    Burn-specific quality of life, measured by the Burn Specific Health Scale-Brief questionnaire (Mandarin Chinese version).

    Total score 152 (0 worst score, 152 best score), consisting of 6 subdomains:

    1) Body imagine (36 points) Simple abilities (36 points) Sexuality (24 points) Affect (32 points) Work (16 points) Interpersonal relationship (8 points)

13. Change in EQ-5D-5L [ Time Frame: Baseline and 12 weeks ]

    Overall quality of life, measured by EQ-5D-5L (Mandarin Chinese version) Total score: 25 points (0 worst score, 25 best score), consisting of 5 subdomains

    1. Mobility (5 points)
    2. Self-care (5 points)
    3. Usual activities (5 points)
    4. pain / discomfort (5 points)
    5. Anxiety / Depression (5 points) EQ overall health assessed on a Visual Analogue Scale, Total 0-100 (0 worst, 100 best score)
14. Number of adverse events [ Time Frame: Baseline and 12 weeks ]
    Recording of complications during exercise: Graft take, Wound infections, Medical, Cardio-respiratory safety

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: David R Schieffelers; +32465419848; david.schieffelers@uantwerp.be

Locations

China, Hubei

Institute of Burns, Wuhan Third Hospital & Tongren Hospital of Wuhan University; Recruiting

Wuhan, Hubei, China, 430060

Contact: Xie Weiguo +8618071085225 wgxie@hotmail.com

Sponsors and Collaborators

Universiteit Antwerpen

Research Foundation Flanders

Wuhan Third Hospital

Investigators

• Principal Investigator: Ulrike Van Daele; Faculty of Medicine and Health Sciences, University of Antwerp

More Information

• Responsible Party: Ulrike Van Daele, Prof. dr., Universiteit Antwerpen
• ClinicalTrials.gov Identifier: NCT04372550
• Other Study ID Numbers: 11B8619N
• First Posted: May 4, 2020
• Last Update Posted: August 12, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Datasets will be made available upon request.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ulrike Van Daele, Universiteit Antwerpen:

Burns; Exercise rehabilitation; Exercise Therapy; Muscle wasting; Hypermetabolism; Insulin resistance

Additional relevant MeSH terms:

Burns; Wounds and Injuries