Electrical Stimulation to Improve Recovery After Peripheral Nerve Injury

Study Overview
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Brief Summary
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After nerve injury and facial palsy, many patients have permanent muscle and sensory dysfunction. Electrical stimulation (ES) of injured nerves may speed up axon growth and improve recovery. This study will assess if ES accelerates motor axon regeneration and improves muscle recovery in patients undergoing two-staged facial reanimation for facial palsy. This study of ES in these patients will investigate: i) nerve regeneration over long distances; ii) direct evidence of changes in nerve regeneration with nerve samples from the second procedure; and iii) changes in functional outcomes in a patient population with much less variability. Our study will provide evidence about the effect of ES in improving outcomes in patients with nerve injuries.

Official Title
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Electrical Stimulation to Improve Recovery After Peripheral Nerve Injury - A Randomized Controlled Prospective Study

Conditions
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Hemifacial Paralysis, Bell Palsy

Intervention / Treatment
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* Device: Electrical Stimulation
* Device: Sham Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing unilateral facial reanimation with a two-stage cross-face nerve graft and free gracilis muscle flap transfer who have; i) isolated unilateral facial nerve palsy and ii) a functioning contralateral facial nerve. Exclusion Criteria: Any disorders that may compromise nerve regeneration or muscle function following muscle transfer, including diabetes, polyneuropathy, or myopathy and muscular dystrophy. Patients with severe cognitive impairment, which would limit their participation

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Electrical Stimulation<br>Electrical Stimulation The patient will receive active electrical stimulation. | Device: Electrical Stimulation<br>* Two-Stage Facial Reanimation (Standard Practice) with electrical stimulation for one hour at 20Hz (Experimental Procedure). Cross-Facial Nerve Graft (CFNG) immediately followed by electrical nerve stimulation proximal to the coaptation site on the donor facial nerve. Nine-to-Twelve Months later, Free Muscle Transfer (FMT) followed by electrical nerve stimulation proximal to the coaptation site in the intraoral incision.<br>|
| Placebo Comparator: Sham Treatment<br>No Electrical Stimulation The patient will receive sham electrical stimulation. | Device: Sham Treatment<br>* Two-Stage Facial Reanimation (Standard Practice) with sham electrical stimulation for one hour (Placebo). Cross-Facial Nerve Graft (CFNG) followed by placement of unelectrified electrodes proximal to the coaptation site on the donor facial nerve. Free Muscle Transfer (FMT) followed by placement of unelectrified electrodes proximal to the coaptation site in the intraoral incision.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pre-Operative Lip Excursion with Smile | FACEGRAM will be used to objectively analyse change in commissure excursion. | Change from Baseline (Pre-Op) over 2 Years | 
| Change in Myelinated Axon Count | The number of myelinated nerve fibres that regenerate and reach the distal CFNG will be compared between groups. | Change from Baseline (Pre-Op) to the Final Surgery 1 Year Later | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Facial Symmetry | FACEGRAM will be used to objectively analyse smile symmetry. | Change from Baseline (Pre-Op) over 2 Years | 
| Facial Clinimetric Evaluation (FaCE) Scores | The Facial Clinimetric Evaluation (FaCE) Scale is a patient-report questionnaire assessing facial impairment and disability associated with facial paralysis. The 15-item likert scale questionnaire consists of six domains: i) facial movement, ii) facial comfort, iii) oral function, iv) eye comfort, v) lacrimal control and vi) social function. Each domain produces its own score, with 1 meaning 'problems all the time' and 5 suggesting 'no problems at all.' The domain scores can then be summed to produce a total score assessing total quality of life with respect to facial paralysis. | Change from Baseline (Pre-Op) Over 2 Years | 
| Time to Reinnervation | Study participants are requested to monitor their facial movements and record any changes in a daily diary once they first notice facial movement. | Up to 1 year after the Second Operation (FMT) | 
| Myelin Thickness | Using histomorphometry, Myelin Thickness will be used as a surrogate measure for the rate of axon regeneration. | Change from Baseline (Pre-Op) to the Final Surgery 1 Year Later | 
| Nerve Fibre Diameter | Using histomorphometry, Nerve Fibre Diameter will be used as a surrogate measure for the rate of axon regeneration. | Change from Baseline (Pre-Op) to the Final Surgery 1 Year Later | 
| Myelin Thickness/Fibre Diameter Ratio | Using histomorphometry, Myelin Thickness/Fibre Diameter Ratio will be used as a surrogate measure for the rate of axon regeneration. | Change from Baseline (Pre-Op) to the Final Surgery 1 Year Later | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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free muscle transfer, FMT, unilateral facial nerve palsy, facial nerve palsy, facial palsy, facial paralysis, cross facial nerve graft, CFNG, peripheral nerve stimulation, electrical stimulation, e-stim