Neuromuscular Electrical Stimulation During Immobilization Due to Ankle Fractures

Study Overview
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Brief Summary
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Rationale: Situations such as fractures of the lower extremity can necessitate a prolonged period of immobilization in otherwise healthy individuals. Long-term immobilization of the lower extremity has shown to cause significant reductions in skeletal muscle mass, already occurring during the early stages of disuse. Accordingly, feasible strategies for attenuating this loss of muscle during disuse need to be pursued. Local neuromuscular electrical stimulation (NMES) offers such a potential strategy but, as yet, remains untested during prolonged muscle disuse in a clinical setting. Objective: To investigate whether twice daily local (gastrocnemius/soleus) NMES attenuates muscle loss during 2 weeks of unilateral ankle immobilization. Study design: Randomized, parallel (two groups) study design. Study population: 30 adults (18-65 y) with any form of closed ankle fractures needing surgical treatment. Intervention: Twice daily neuromuscular electrical stimulation (NMES) or no intervention. Main study parameters/endpoints: Primary: Calf muscle (gastrocnemius) cross sectional area (CSA) as determined by CT scan. Secondary: type I and II muscle fiber CSA and SC content, intramuscular triglyceride content and mRNA and protein expression of anabolic signaling proteins.

Official Title
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The Effects of Daily Neuromuscular Electrical Stimulation on Muscle Mass During Long-term Unilateral Ankle Immobilization in Adults With Ankle Fractures

Conditions
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Immobilization, Muscle Disuse Atrophy

Intervention / Treatment
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* Device: Neuromuscular Electrical Stimulation (NMES)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unilateral closed ankle fracture (Weber type A, B or C) Aged from 18-65 years 18.5 < BMI < 30 kg/m2 Undergoing surgical treatment Exclusion Criteria: Additional fractures beside ankle fracture (e.g. multi-trauma following a car accident) Use of oral anticoagulants such as vitamin K-antagonists (e.g. acenocoumarol and fenprocoumon) and direct-acting or new oral anticoagulants (e.g. apixaban, dabigatran and rivaroxaban). Any family history of thrombosis All co-morbidities interacting with mobility and muscle metabolism of the lower limbs (e.g. arthritis, spasticity/rigidity, all neurological disorders and paralysis). Myocardial infarction within the last 3 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NMES group<br>Patients will receive twice daily sessions of neuromuscular electrical stimulation (NMES). | Device: Neuromuscular Electrical Stimulation (NMES)<br>* The protocol will consist of a warm-up period (5 min), a stimulation period (30min), and a cooling-down period (5min). Stimulation will be provided by an Enraf Nonius TensMed S84 stimulation device.<br>|
| No Intervention: Control group<br>Patients will receive daily visits by the investigator to check progress. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in calf muscle cross sectional area | Measured by a single slice CT-scan of the calf muscle. | Baseline measurements will be performed at the day of the surgical intervention for the ankle fracture. Post measurements will be performed at the last day of the subsequent 2-week period of immobilization with a lower leg cast. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in type I and II muscle fiber cross sectional area | Measured by immunohistochemical analyses of the muscle biopsies. | Baseline measurements will be performed at the day of the surgical intervention for the ankle fracture. Post measurements will be performed at the last day of the subsequent 2-week period of immobilization with a lower leg cast. | 
| Percentage change in type I and II muscle fiber satellite cell content | Measured by immunohistochemical analyses of the muscle biopsies. | Baseline measurements will be performed at the day of the surgical intervention for the ankle fracture. Post measurements will be performed at the last day of the subsequent 2-week period of immobilization with a lower leg cast. | 
| Percentage change in type I and II muscle fiber intramuscular triglyceride content | Measured by immunohistochemical analyses of the muscle biopsies. | Baseline measurements will be performed at the day of the surgical intervention for the ankle fracture. Post measurements will be performed at the last day of the subsequent 2-week period of immobilization with a lower leg cast. |