Dysport for the Treatment of OMD

Study Overview
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Brief Summary
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The purpose of this study is to study the efficacy and safety of AbobotulinumtoxinA (Dysport) for use in Oromandibular Dystonia (OMD).

Detailed Description
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Oromandibular dystonia (OMD) is an uncommon, disabling form of cranial dystonia, involving involuntary movements of the lower facial, masticatory, and lingual muscles. This can cause jaw movements including opening, closure, protrusion, retraction, or deviation. Common additional facial movements involve grimacing or lip pursing. When there is tongue involvement, it usually presents as tongue protrusion or curling. Such patients are impaired in relation to eating, speaking and swallowing This study aims to evaluate the efficacy and safety of a low dose of Dysport® deemed tolerable during phase 1 in subjects with oromandibular dystonia (OMD). Participants will be injected with Dysport® only, with an unblinded open-label disclosure. The safety and efficacy pf receiving Dysport® will be recorded for all subjects that undergo injection. All subjects will be examined and videotaped at the injection visit, then at 6 and 12 weeks after injection with a standardized protocol. The primary outcome will be blinded examination scores of the videos performed after the study is complete.The evaluators will be three different movement disorders experts, not otherwise involved in the study, who will review the videotaped examinations, presented in a random order, using the Global Dystonia Rating scale (GDS). Evaluators will rate the dystonia at baseline (injection visit) and 6 weeks after injection.

Official Title
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A Pilot Dose Ranging Study of Dysport® (AbobotulinumtoxinA) in the Treatment of Oromandibular Dystonia

Conditions
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Oral Dystonia, Tardive Dystonia

Intervention / Treatment
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* Drug: Low Dose - AbobotulinumtoxinA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a diagnosis of primary or tardive OMD moderate or severe severity, defined as GDS score ≥4 in either lower face or jaw and tongue section capability of attending the scheduled visits only those who have been previously injected with onabotulinumtoxinA and responded to that treatment, and are at least 12 weeks post last injection Women of childbearing age need to use contraception in order to be included. Exclusion Criteria: Existence of a systemic disease that could confound the evaluation previous placement of Deep Brain Stimulation electrodes to treat dystonia concomitant oral medications that could interfere with the action of botulinum toxin Type A (e.g., aminoglycosides) on an unstable dosage of any medication prescribed to treat dystonia (e.g., benzodiazepines, baclofen or anticholinergics) any known hypersensitivity to any botulinum toxin preparation and allergy to cow's milk protein immunoresistance to other forms of botulinum toxin type A existence of a concomitant neuromuscular disorder (e.g., Myasthenia Gravis or Lambert-Eaton syndrome, etc) infection at the proposed injection sites pregnant women women of childbearing age NOT on contraception breastfeeding women inability to comply with scheduled visits patients who had been previously injected with botulinum toxin type A but who did not respond

Ages Eligible for Study
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Minimum 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dysport Injections<br>Participants with OMD who have been previously treated with any botulinum toxin Type A will be injected with Dysport®. | Drug: Low Dose - AbobotulinumtoxinA<br>* Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units<br>* Other names: Dysport;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Global Dystonia Rating Scale Score as Measured by Blinded Rater | This scale measures the severity of dystonia for the jaw and tongue by a blinded rater. Dystonia is rated from 0 to 10: 0=No dystonia present, 1=Minimal dystonia, 5=Moderate dystonia,10=Most severe dystonia | Baseline, Week 6, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Analogue Pain Scale Score | Measure of jaw pain by visual analogue scale (0-100) where 0 represents no pain and 100 represents the most severe pain. | Baseline, Week 12 | 
| Mean Sialorrhea Clinical Scale for Parkinson's Disease (SCS-PD) Score | The SCS-PD measures drooling. Individual items are scored on a scale from 0-3 where 0 represents never and 3 represents always. The overall maximum score is 21. A higher score indicates greater drooling severity. A lower score indicates lesser severity. | Baseline, Week 6, Week 12 | 
| Change in Number of Tongue Bites Per Day | The patient will be asked to estimate how many times they tend to accidentally/involuntarily bite their tongue per day. | Baseline, Week 12 | 
| Mean Swallowing Disturbance Questionnaire (SDQ-20) Score | Ease of chewing and swallowing will be assessed by the SDQ-20 (modified to exclude question 5 due to redundancy as it relates to drooling and question 15 which is not relevant to the study as it involves prior aspiration pneumonias). Individual items are scored from 0 (never) to 3 (very frequently). The overall score is the total for all items; a higher score indicating more frequent swallowing disturbance; a lower score indicating no or less frequent disturbance, with a possible maximum score of 39. | Baseline, Week 6, Week 12 | 
| Mean Fahn-Marsden Part B Speech Question (BFM-q21) Rating | The Fahn-Marsden Part B Speech Question assesses the ease of producing speech. Responses range from 0=Normal, 1=Slightly involved, easily understood, 2=Some difficulty understanding, 3=Marked difficulty understanding. | Baseline, Week 6, Week 12 | 
| Mean Oromandibular Dystonia Quality of Life Questionnaire (OMDQ-25) Score | The OMDQ-25 is a subjective quality of life measurement made for patients with Oromandibular Dystonia. The maximum total score is 100 indicating the highest quality of life. A score of 50 indicates a mediocre quality of life. A lower score indicates perceived lower quality of life. | Baseline, Week 6, Week 12 | 
| Mean Global Clinical Impression - Improvement Scale (CGI) Index Score | The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. Responses are scored on a scale from 1 to 7; 1 represents very much improved and 7 represents very much worse. | Week 6, Week 12 | 
| Mean Global Clinical Impression Scale (CGI-S) With Severity Index Score | The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Responses are scored on a scale from 1 to 7; 1 represents normal, not at all ill and 7 represents among the most extremely ill patients. | Baseline, Week 6, Week 12 | 
| Mean Global Clinical Impression- Efficacy Index Score | The Clinical Global Impression - Efficacy Index is a 4×4 rating scale that assesses the therapeutic effect of treatment. Responses range on a scale from 0 to 4 with 4 being the best response. | Week 6, Week 12 | 
| Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Un-blinded Rater | The UDRS measures dystonia severity. The UDRS is being rated by un-blinded video evaluators regarding severity of subject's dystonia. Scores range from 0 to 10; 0 indicating no dystonia, 5 indicating moderate dystonia, and 10 indicating the worst dystonia. | Baseline, Week 6, Week 12 | 
| Mean Global Dystonia Rating Scale Score as Measured by Un-blinded Rater | This scale measures the severity of dystonia for the jaw and tongue by an un-blinded rater. Dystonia is rated from 0 to 10: 0=No dystonia present, 1=Minimal dystonia, 5=Moderate dystonia,10=Most severe dystonia | Baseline, Week 6, Week 12 | 
| Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Blinded Rater | The UDRS measures dystonia severity. The UDRS is being rated by blinded video evaluators regarding severity of subject's dystonia. Scores range from 0 to 10; 0 indicating no dystonia, 5 indicating moderate dystonia, and 10 indicating the worst dystonia. | Baseline, Week 6, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oromandibular Dystonia, Oral Dystonia, Tardive Dystonia, botulinum toxin, abobotulinumtoxinA