Dysport for the Treatment of OMD

• ClinicalTrials.gov Identifier: NCT01921270
• Recruitment Status: Completed
• First Posted: August 13, 2013
• Results First Posted: November 17, 2017
• Last Update Posted: November 17, 2017
• Sponsor: Emory University
• Collaborator: Ipsen
• Information provided by (Responsible Party): Stewart Factor, Emory University

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Oral Dystonia; Tardive Dystonia	Drug: Low Dose - AbobotulinumtoxinA	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: Evaluators will review the videotaped examinations, presented in a random order, using the Global Dystonia Rating scale (GDS). The evaluators will rate the dystonia at baseline (injection visit) and 6 weeks after injection.
• Primary Purpose: Treatment
• Official Title: A Pilot Dose Ranging Study of Dysport® (AbobotulinumtoxinA) in the Treatment of Oromandibular Dystonia
• Study Start Date: August 2013
• Actual Primary Completion Date: February 8, 2017
• Actual Study Completion Date: February 8, 2017

Arms and Interventions

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 Name: Dysport

Outcome Measures

Primary Outcome Measures :

1. Mean Global Dystonia Rating Scale Score as Measured by Blinded Rater [ Time Frame: Baseline, Week 6, Week 12 ]

   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

Secondary Outcome Measures :

1. Change in Analogue Pain Scale Score [ Time Frame: Baseline, Week 12 ]
   Measure of jaw pain by visual analogue scale (0-100) where 0 represents "no pain" and 100 represents the "most severe pain".
2. Mean Sialorrhea Clinical Scale for Parkinson's Disease (SCS-PD) Score [ Time Frame: Baseline, Week 6, Week 12 ]
   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.
3. Change in Number of Tongue Bites Per Day [ Time Frame: Baseline, Week 12 ]
   The patient will be asked to estimate how many times they tend to accidentally/involuntarily bite their tongue per day.
4. Mean Swallowing Disturbance Questionnaire (SDQ-20) Score [ Time Frame: Baseline, Week 6, Week 12 ]
   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.
5. Mean Fahn-Marsden Part B "Speech" Question (BFM-q21) Rating [ Time Frame: Baseline, Week 6, Week 12 ]
   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.
6. Mean Oromandibular Dystonia Quality of Life Questionnaire (OMDQ-25) Score [ Time Frame: Baseline, Week 6, Week 12 ]
   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.
7. Mean Global Clinical Impression - Improvement Scale (CGI) Index Score [ Time Frame: Week 6, Week 12 ]
   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".
8. Mean Global Clinical Impression Scale (CGI-S) With Severity Index Score [ Time Frame: Baseline, Week 6, Week 12 ]
   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".
9. Mean Global Clinical Impression- Efficacy Index Score [ Time Frame: Week 6, Week 12 ]
   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.
10. Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Un-blinded Rater [ Time Frame: Baseline, Week 6, Week 12 ]
    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.
11. Mean Global Dystonia Rating Scale Score as Measured by Un-blinded Rater [ Time Frame: Baseline, Week 6, Week 12 ]

    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

12. Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Blinded Rater [ Time Frame: Baseline, Week 6, Week 12 ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Georgia

Wesley Woods Health Center; Emory University Hospital

Atlanta, Georgia, United States, 30329

Sponsors and Collaborators

Emory University

Ipsen

Investigators

• Principal Investigator: Stewart A Factor, DO; Emory University

  Study Documents (Full-Text)

Documents provided by Stewart Factor, Emory University:

Study Protocol and Statistical Analysis Plan  [PDF] March 3, 2015

More Information

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.

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®) injections for oromandibular, lingual, and truncal-axial dystonias. Int J Neurosci. 2011;121 Suppl 1:44-56. doi: 10.3109/00207454.2011.558260.

• Responsible Party: Stewart Factor, Professor, Emory University
• ClinicalTrials.gov Identifier: NCT01921270
• Other Study ID Numbers: IRB00064292
• First Posted: August 13, 2013
• Results First Posted: November 17, 2017
• Last Update Posted: November 17, 2017
• Last Verified: October 2017

Keywords provided by Stewart Factor, Emory University:

Oromandibular Dystonia; Oral Dystonia; Tardive Dystonia; botulinum toxin; abobotulinumtoxinA

Additional relevant MeSH terms:

Dystonia; Dystonic Disorders; Tardive Dyskinesia; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Movement Disorders; Central Nervous System Diseases; Dyskinesia, Drug-Induced; abobotulinumtoxinA; Botulinum Toxins, Type A; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents