Mixed Methods Investigation of Chronic Facial Paralysis in Individuals With Synkinesis

Phase 4

Completed

Conditions: Synkinesis

Interventions: Drug: Chemodenervation (4 months)
Other: Neuromuscular Retraining Therapy (4 months)
Other: Neuromuscular Retraining + Chemodenervation

Registration Number: NCT04148872

Lead Sponsor: University of Wisconsin, Madison

Brief Summary: This proposal will prospectively assess the social, physical, and emotional recognition function in participants with synkinesis. It will measure the effectiveness of neuromuscular retraining therapy to improve muscle coordination compared to chemodenervation, the more established treatment modality, in a single-blinded, randomized control trial using clinician- and patient-reported outcomes measures. The hypothesis tested is that participants undergoing neuromuscular retraining therapy will achieve greater improvement on clinical outcome measures as compared to participants receiving chemodenervation.

In this clinical trial, 36 participants undergoing treatment for synkinesis will be enrolled into one of two treatment arms: chemodenervation or neuromuscular retraining therapy. Participants can expect to be on study for approximately 8 months.

Participants who enroll in this mixed methods investigation will be recruited from patients of the University of Wisconsin Facial Nerve Clinic and also be enrolled in a another study for assessment \[Perception of Emotion Expression in Clinical Populations with Facial Paralysis, IRB approval 2015-0366\].

Detailed Description: Facial nerve paralysis is a devastating event that in up to 30% of cases may result in chronic weakness and/or the disfiguring condition of synkinesis, a long-lasting muscle discoordination of facial movement caused by aberrant facial nerve regeneration after facial nerve paralysis. This is believed to have a detrimental effect on social interactions, mental health, and quality of life.

Neuromuscular retraining therapy and ipsilateral chemodenervation into discoordinated muscles by injection (onabotulinumtoxinA/Botox, Allergan or incobotulinumtoxinA/Xeomin, Merz) are two common treatments for the abnormal muscle movements found in synkinesis. No study has compared the effectiveness of these treatment modalities for synkinesis. Retrospective data including our series at the University of Wisconsin Facial Nerve Clinic show significant benefit of retraining therapy using clinician- and patient-reported outcome measures. However, the manner in which this therapy may be optimized for use in treatment of the sequelae of facial paralysis is unclear. While literature shows beneficial improvement in outcomes with chemodenervation in prospective studies, no study has explored the effectiveness of physical therapy for synkinesis in a controlled, prospective manner. Further, the efficacy of therapy has not been shown to improve recognition and emotional information interpretation, both thought to be impaired in synkinesis.

This study has 3 specific aims:

AIM 1: Determine the effect of neuromuscular retraining or chemodenervation on clinician-reported and patient-reported outcomes. The primary outcome measure after four and eight months of treatment will be the clinician-reported Sunnybrook Facial Grading System (SFGS) scored on participant videos by blinded reviewers. Further, the investigators seek to measure the efficacy of treatment with existing patient-reported instruments. A correlation of clinician-reported outcome measure changes to changes in patient-reported instruments with treatment will be calculated, including the widely utilized disease specific Synkinesis Assessment Questionnaire (SAQ) and Facial Clinimetric Evaluation Scale (FaCE), and with two disease non-specific instruments, the Hospital Anxiety and Depression Scale (HADS), and Brief-Illness Perception Questionnaire (BIPQ). The efficacy of our clinical intervention will be measured with social-perceptual and mental health outcome measurement before and after treatment (AIM 3).

AIM 2: Determine the social, emotional, and functional burden of synkinesis, not captured in current patient-reported outcome measures as well as effect of treatment. Qualitative interviews with individual participants collected before treatment, after four months of treatment, and after eight months of treatment will be analyzed to study the burden of disease, experience with treatment, and potential differences in both treatments. The primary outcome is to identify the domains that may be missing from existing patient-reported measures collected in AIM 1. To do this, findings to assessment domains (i.e. decreased engagement, negative mood, etc.) in the FaCE, SAQ, and the two disease non-specific instruments, HADS and BIPQ will be compared. The investigators will then evaluate their findings based on domains in Patient-Reported Outcomes Measurement Information System (PROMIS) measures, an NIH-supported collection of validated and standardized scales.

AIM 3: Quantify the disruption in social functioning caused by synkinesis using innovative social-perceptual outcomes and emotion recognition tasks. Prior to treatment, participants will enroll in IRB Protocol 2015-0366 and complete a series of social functioning and mental health instruments and emotion expression recognition tasks. Results will be compared to control participants without facial disability to reveal the social-perceptual impairment attributable to synkinesis. Repetition of these tasks after four months of either treatment may show improvement in recognition and emotional information interpretation when compared to initial measurements.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15

Inclusion Criteria

Has ipsilateral synkinesis of facial muscles
It has been at least four months since their onset of peripheral facial paralysis from any cause
Ability to read and write in English

Exclusion Criteria

previous treatment with reanimation surgery (except for upper eyelid weight placement)
intolerance or contraindication to botulinum toxin injection
previous treatment for synkinesis with chemodenervation or neuromuscular retraining therapy
pregnant and/or breastfeeding women
participants with impaired decision-making capacity, including those with severe psychiatric illnesses

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemodenervation	Chemodenervation (4 months)	Ipsilateral chemodenervation with botulinum toxin injections alone for four months (onabotulinumtoxinA/Botox, Allergan or incobotulinumtoxinA/Xeomin, Merz), with neuromuscular retraining therapy added for an additional four months.
Neuromuscular Retraining Therapy	Neuromuscular Retraining Therapy (4 months)	Neuromuscular retraining therapy alone for four months, with botulinum toxin injection added during an additional four month period.
Chemodenervation	Neuromuscular Retraining + Chemodenervation	Ipsilateral chemodenervation with botulinum toxin injections alone for four months (onabotulinumtoxinA/Botox, Allergan or incobotulinumtoxinA/Xeomin, Merz), with neuromuscular retraining therapy added for an additional four months.
Neuromuscular Retraining Therapy	Neuromuscular Retraining + Chemodenervation	Neuromuscular retraining therapy alone for four months, with botulinum toxin injection added during an additional four month period.

Primary Outcome Measures

Name	Time	Method
Sunnybrook Facial Grading System (SFGS) at Baseline	Baseline	Participants will be videotaped as part of routine care and undergo a blinded SFGS scoring. Scoring is determined by a voluntary movement score (5-items scored from 1-5 where 1 is unable to move and 5 is complete voluntary movement - total range of 5-25, multiplied by 4, where a higher score is a better outcome) minus a resting symmetry score (total of 0-4 where 0 is normal and 4 indicates some asymmetry, multiplied by 5, where a lower score is a better outcome) minus a synkinesis score (5-items scored from 0-3 where 0 is none and 3 is severe, a lower score is a better outcome). Total possible range of scores is 20-100, with a higher score being a better outcome.
Sunnybrook Facial Grading System (SFGS) at 8 Months	8 months	Participants will be videotaped as part of routine care and undergo a blinded SFGS scoring. Scoring is determined by a voluntary movement score (5-items scored from 1-5 where 1 is unable to move and 5 is complete voluntary movement - total range of 5-25, multiplied by 4, where a higher score is a better outcome) minus a resting symmetry score (total of 0-4 where 0 is normal and 4 indicates some asymmetry, multiplied by 5, where a lower score is a better outcome) minus a synkinesis score (5-items scored from 0-3 where 0 is none and 3 is severe, a lower score is a better outcome). Total possible range of scores is 20-100, with a higher score being a better outcome.
Change in Sunnybrook Facial Grading System (SFGS) Between Baseline and 4 Month Scoring	up to 4 months	Participants will be videotaped as part of routine care and undergo a blinded SFGS scoring. Scoring is determined by a voluntary movement score (5-items scored from 1-5 where 1 is unable to move and 5 is complete voluntary movement - total range of 5-25, multiplied by 4, where a higher score is a better outcome) minus a resting symmetry score (total of 0-4 where 0 is normal and 4 indicates some asymmetry, multiplied by 5, where a lower score is a better outcome) minus a synkinesis score (5-items scored from 0-3 where 0 is none and 3 is severe, a lower score is a better outcome). Total possible range of scores is 20-100, with a higher score being a better outcome. Scores from baseline will be compared to those at 4 months and the change between the two will be reported.
Sunnybrook Facial Grading System (SFGS) at 4 Months	4 months	Participants will be videotaped as part of routine care and undergo a blinded SFGS scoring. Scoring is determined by a voluntary movement score (5-items scored from 1-5 where 1 is unable to move and 5 is complete voluntary movement - total range of 5-25, multiplied by 4, where a higher score is a better outcome) minus a resting symmetry score (total of 0-4 where 0 is normal and 4 indicates some asymmetry, multiplied by 5, where a lower score is a better outcome) minus a synkinesis score (5-items scored from 0-3 where 0 is none and 3 is severe, a lower score is a better outcome). Total possible range of scores is 20-100, with a higher score being a better outcome.

Secondary Outcome Measures

Name	Time	Method
Synkinesis Assessment Questionnaire (SAQ) at Baseline	Baseline	The SAQ is a 9-item questionnaire where each item is scored on a scale from 1-5, 1 is seldom or not at all, and 5 is all of the time, or severely. A higher score indicates a worse outcome. The total range in possible scores is 9-100 (summate scores for questions 1-9/45x100 = SAQ total score) with higher scores indicating more severe facial paralysis symptoms. SAQ scores will be collected as part of routine care throughout the study. Scores will be reported for baseline, 4 months (mid-study), and 8 months (end of study).
Synkinesis Assessment Questionnaire (SAQ) at 4 Months	4 months	The SAQ is a 9-item questionnaire where each item is scored on a scale from 1-5, 1 is seldom or not at all, and 5 is all of the time, or severely. A higher score indicates a worse outcome. The total range in possible scores is 9-100 (summate scores for questions 1-9/45x100 = SAQ total score) with higher scores indicating more severe facial paralysis symptoms. SAQ scores will be collected as part of routine care throughout the study. Scores will be reported for baseline, 4 months (mid-study), and 8 months (end of study).
Synkinesis Assessment Questionnaire (SAQ) at 8 Months	8 months	The SAQ is a 9-item questionnaire where each item is scored on a scale from 1-5, 1 is seldom or not at all, and 5 is all of the time, or severely. A higher score indicates a worse outcome. The total range in possible scores is 9-100 (summate scores for questions 1-9/45x100 = SAQ total score) with higher scores indicating more severe facial paralysis symptoms. SAQ scores will be collected as part of routine care throughout the study. Scores will be reported for baseline, 4 months (mid-study), and 8 months (end of study).
Facial Clinimetric Evaluation Scale (FaCE) at Baseline	Baseline	The FaCE scale is 15-item self-report survey to assess the symptoms of facial paralysis in the past week. The total possible range of scores is 15-100 where the higher the score, the lesser the symptoms. Scores will be reported for baseline, 4 months (mid-study), and 8 months (end of study).
Facial Clinimetric Evaluation Scale (FaCE) at 4 Months	4 months	The FaCE scale is 15-item self-report survey to assess the symptoms of facial paralysis in the past week. The total possible range of scores is 15-100 where the higher the score, the lesser the symptoms. Scores will be reported for baseline, 4 months (mid-study), and 8 months (end of study).
Facial Clinimetric Evaluation Scale (FaCE) at 8 Months	up to 8 months	The FaCE scale is 15-item self-report survey to assess the symptoms of facial paralysis in the past week. The total possible range of scores is 15-100 where the higher the score, the lesser the symptoms. Scores will be reported for baseline, 4 months (mid-study), and 8 months (end of study).
Hospital Anxiety and Depression Scale (HADS) at Baseline	Baseline	The HADS instrument measures anxiety and depressive tendency. 7-items are scored for depression with a total score of 0-21 where the higher the score, the more symptoms of depression. 7-items are scored for anxiety with a total score of 0-21 where the higher the score, the more symptoms of anxiety. Scores will be reported for baseline, 4 months (mid-study), and 8 months (end of study).
Hospital Anxiety and Depression Scale (HADS) at 4 Months	4 months	The HADS instrument measures anxiety and depressive tendency. 7-items are scored for depression with a total score of 0-21 where the higher the score, the more symptoms of depression. 7-items are scored for anxiety with a total score of 0-21 where the higher the score, the more symptoms of anxiety. Scores will be reported for baseline, 4 months (mid-study), and 8 months (end of study).
Brief-Illness Perception Questionnaire (BIPQ) at 8 Months	up to 8 months	The BIPQ is a 9-item questionnaire, where the first 8-items are scored from 0-10. To determine a composite score, items 3, 4, and 7 should be reversed scored and added to 1, 2, 5, 6, and 8 (total range of possible scores from 0-80). The higher the score the more threatening the illness is perceived to be. Scores will be reported for baseline, 4 months (mid-study), and 8 months (end of study).
Pre-Treatment Qualitative Interviews	up to 8 months	Qualitative analysis will proceed concurrently with data collection to allow identified themes to be explored in subsequent interviews. In qualitative research this involves both coding the written transcripts and then modeling the coded data. All team members will analyze the data and look for themes and trends that are emergent from the data. For the pre-treatment interviews, Conventional Content Analysis will be employed to obtain direct information from study participants without imposing preconceived categories or theoretical perspectives.
Post-Treatment Qualitative Interviews	up to 4 months	Qualitative analysis will proceed concurrently with data collection to allow identified themes to be explored in subsequent interviews. In qualitative research this involves both coding the written transcripts and then modeling the coded data. All team members will analyze the data and look for themes and trends that are emergent from the data. For post-treatment interviews, directed content analysis will be employed as findings from pre-treatment interviews will guide analysis of post-treatment interviews while capturing emergent themes that come up in the data.
Hospital Anxiety and Depression Scale (HADS) at 8 Months	8 months	The HADS instrument measures anxiety and depressive tendency. 7-items are scored for depression with a total score of 0-21 where the higher the score, the more symptoms of depression. 7-items are scored for anxiety with a total score of 0-21 where the higher the score, the more symptoms of anxiety. Scores will be reported for baseline, 4 months (mid-study), and 8 months (end of study).
Brief-Illness Perception Questionnaire (BIPQ) at Baseline	Baseline	The BIPQ is a 9-item questionnaire, where the first 8-items are scored from 0-10. To determine a composite score, items 3, 4, and 7 should be reversed scored and added to 1, 2, 5, 6, and 8 (total range of possible scores from 0-80). The higher the score the more threatening the illness is perceived to be. Scores will be reported for baseline, 4 months (mid-study), and 8 months (end of study).
Brief-Illness Perception Questionnaire (BIPQ) at 4 Months	4 months	The BIPQ is a 9-item questionnaire, where the first 8-items are scored from 0-10. To determine a composite score, items 3, 4, and 7 should be reversed scored and added to 1, 2, 5, 6, and 8 (total range of possible scores from 0-80). The higher the score the more threatening the illness is perceived to be. Scores will be reported for baseline, 4 months (mid-study), and 8 months (end of study).