Dysport for the Treatment of OMD

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

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

Study Overview

• Status: Completed
• Conditions: Tardive Dystonia; Oral Dystonia
• Intervention / Treatment: Drug: Low Dose - AbobotulinumtoxinA

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Wesley Woods Health Center; Emory University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Dysport Injections; Participants with OMD who have been previously treated with any botulinum toxin Type A will be injected with Dysport®.

Drug: Low Dose - AbobotulinumtoxinA; 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; Other Names: Dysport

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Ipsen
• Investigators: Principal Investigator: Stewart A Factor, DO, Emory University

Publications and helpful links

General Publications

• Tan EK, Jankovic J. Botulinum toxin A in patients with oromandibular dystonia: long-term follow-up. Neurology. 1999 Dec 10;53(9):2102-7. doi: 10.1212/wnl.53.9.2102.
• Rosales RL, Ng AR, Santos MM, Fernandez HH. The broadening application of chemodenervation in X-linked dystonia-parkinsonism (Part II): an open-label experience with botulinum toxin-A (Dysport(R)) injections for oromandibular, lingual, and truncal-axial dystonias. Int J Neurosci. 2011;121 Suppl 1:44-56. doi: 10.3109/00207454.2011.558260.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ACTUAL): February 8, 2017
• Study Completion (ACTUAL): February 8, 2017

Study Registration Dates

• First Submitted: August 9, 2013
• First Submitted That Met QC Criteria: August 12, 2013
• First Posted (ESTIMATE): August 13, 2013

Study Record Updates

• Last Update Posted (ACTUAL): November 17, 2017
• Last Update Submitted That Met QC Criteria: October 19, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: botulinum toxin; abobotulinumtoxinA; Oromandibular Dystonia; Oral Dystonia; Tardive Dystonia
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Dyskinesia, Drug-Induced; Tardive Dyskinesia; Dystonia; Dystonic Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: IRB00064292