Oral Dystonia, Tardive Dystonia
Conditions
Keywords
Oromandibular Dystonia, Oral Dystonia, Tardive Dystonia, botulinum toxin, abobotulinumtoxinA
Brief summary
The purpose of this study is to study the efficacy and safety of AbobotulinumtoxinA (Dysport) for use in Oromandibular Dystonia (OMD).
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.
Interventions
DRUGLow 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
Sponsors
Ipsen
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Global Dystonia Rating Scale Score as Measured by Blinded Rater | 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
| Measure | Time frame | Description |
|---|---|---|
| Mean Sialorrhea Clinical Scale for Parkinson's Disease (SCS-PD) Score | 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. |
| Change in Number of Tongue Bites Per Day | Baseline, Week 12 | The patient will be asked to estimate how many times they tend to accidentally/involuntarily bite their tongue per day. |
| Mean Swallowing Disturbance Questionnaire (SDQ-20) Score | 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. |
| Mean Fahn-Marsden Part B Speech Question (BFM-q21) Rating | 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. |
| Mean Oromandibular Dystonia Quality of Life Questionnaire (OMDQ-25) Score | 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. |
| Change in Analogue Pain Scale Score | 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. |
| Mean Global Clinical Impression Scale (CGI-S) With Severity Index Score | 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. |
| Mean Global Clinical Impression- Efficacy Index Score | 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. |
| Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Un-blinded Rater | 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. |
| Mean Global Dystonia Rating Scale Score as Measured by Un-blinded Rater | 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 |
| Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Blinded Rater | 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. |
| Mean Global Clinical Impression - Improvement Scale (CGI) Index Score | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dysport Injections Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®.
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 | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Dysport Injections | — |
|---|---|---|
| Age, Continuous | 62.83 years STANDARD_DEVIATION 10.45 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 18 Participants | — |
| Sex: Female, Male Female | 12 Participants | — |
| Sex: Female, Male Male | 6 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 9 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
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
Time frame: Baseline, Week 6, Week 12
Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport Injections | Mean Global Dystonia Rating Scale Score as Measured by Blinded Rater | Baseline | 3.80 units on a scale | Standard Deviation 2.29 |
| Dysport Injections | Mean Global Dystonia Rating Scale Score as Measured by Blinded Rater | Week 6 | 3.57 units on a scale | Standard Deviation 2.05 |
| Dysport Injections | Mean Global Dystonia Rating Scale Score as Measured by Blinded Rater | Week 12 | 3.71 units on a scale | Standard Deviation 2.18 |
Secondary
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.
Time frame: Baseline, Week 12
Population: Data were not collected.
Secondary
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.
Time frame: Baseline, Week 12
Population: Data were not collected.
Secondary
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.
Time frame: Baseline, Week 6, Week 12
Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport Injections | Mean Fahn-Marsden Part B Speech Question (BFM-q21) Rating | Baseline | 1.33 units on a scale | Standard Deviation 0.91 |
| Dysport Injections | Mean Fahn-Marsden Part B Speech Question (BFM-q21) Rating | Week 6 | .94 units on a scale | Standard Deviation 0.87 |
| Dysport Injections | Mean Fahn-Marsden Part B Speech Question (BFM-q21) Rating | Week 12 | .94 units on a scale | Standard Deviation 0.75 |
Secondary
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.
Time frame: Week 6, Week 12
Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport Injections | Mean Global Clinical Impression- Efficacy Index Score | Week 12 | 1.93 units on a scale | Standard Deviation 0.97 |
| Dysport Injections | Mean Global Clinical Impression- Efficacy Index Score | Week 6 | 1.51 units on a scale | Standard Deviation 0.93 |
Secondary
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.
Time frame: Week 6, Week 12
Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport Injections | Mean Global Clinical Impression - Improvement Scale (CGI) Index Score | Week 6 | 2.89 units on a scale | Standard Deviation 1.28 |
| Dysport Injections | Mean Global Clinical Impression - Improvement Scale (CGI) Index Score | Week 12 | 2.53 units on a scale | Standard Deviation 0.87 |
Secondary
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.
Time frame: Baseline, Week 6, Week 12
Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport Injections | Mean Global Clinical Impression Scale (CGI-S) With Severity Index Score | Baseline | 4.06 units on a scale | Standard Error 1 |
| Dysport Injections | Mean Global Clinical Impression Scale (CGI-S) With Severity Index Score | Week 6 | 3.22 units on a scale | Standard Error 1.11 |
| Dysport Injections | Mean Global Clinical Impression Scale (CGI-S) With Severity Index Score | Week 12 | 3.29 units on a scale | Standard Error 0.92 |
Secondary
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
Time frame: Baseline, Week 6, Week 12
Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport Injections | Mean Global Dystonia Rating Scale Score as Measured by Un-blinded Rater | Baseline | 5.67 units on a scale | Standard Deviation 1.53 |
| Dysport Injections | Mean Global Dystonia Rating Scale Score as Measured by Un-blinded Rater | Week 6 | 3.94 units on a scale | Standard Deviation 2.1 |
| Dysport Injections | Mean Global Dystonia Rating Scale Score as Measured by Un-blinded Rater | Week 12 | 3.76 units on a scale | Standard Deviation 2.25 |
Secondary
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.
Time frame: Baseline, Week 6, Week 12
Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport Injections | Mean Oromandibular Dystonia Quality of Life Questionnaire (OMDQ-25) Score | Baseline | 47.39 units on a scale | Standard Deviation 23 |
| Dysport Injections | Mean Oromandibular Dystonia Quality of Life Questionnaire (OMDQ-25) Score | Week 6 | 43.22 units on a scale | Standard Deviation 23.24 |
| Dysport Injections | Mean Oromandibular Dystonia Quality of Life Questionnaire (OMDQ-25) Score | Week 12 | 38.00 units on a scale | Standard Deviation 21.42 |
Secondary
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.
Time frame: Baseline, Week 6, Week 12
Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport Injections | Mean Sialorrhea Clinical Scale for Parkinson's Disease (SCS-PD) Score | Baseline | 3.00 units on a scale | Standard Deviation 3.91 |
| Dysport Injections | Mean Sialorrhea Clinical Scale for Parkinson's Disease (SCS-PD) Score | Week 12 | 2.53 units on a scale | Standard Deviation 3.2 |
| Dysport Injections | Mean Sialorrhea Clinical Scale for Parkinson's Disease (SCS-PD) Score | Week 6 | 2.72 units on a scale | Standard Deviation 4.28 |
Secondary
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.
Time frame: Baseline, Week 6, Week 12
Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport Injections | Mean Swallowing Disturbance Questionnaire (SDQ-20) Score | Baseline | 13.17 units on a scale | Standard Deviation 9.51 |
| Dysport Injections | Mean Swallowing Disturbance Questionnaire (SDQ-20) Score | Week 6 | 15.61 units on a scale | Standard Deviation 8.56 |
| Dysport Injections | Mean Swallowing Disturbance Questionnaire (SDQ-20) Score | Week 12 | 13.29 units on a scale | Standard Deviation 8.54 |
Secondary
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.
Time frame: Baseline, Week 6, Week 12
Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport Injections | Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Blinded Rater | Baseline | 3.50 units on a scale | Standard Deviation 1.92 |
| Dysport Injections | Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Blinded Rater | Week 6 | 3.47 units on a scale | Standard Deviation 1.79 |
| Dysport Injections | Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Blinded Rater | Week 12 | 3.30 units on a scale | Standard Deviation 1.72 |
Secondary
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.
Time frame: Baseline, Week 6, Week 12
Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dysport Injections | Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Un-blinded Rater | Baseline | 4.67 units on a scale | Standard Deviation 1.15 |
| Dysport Injections | Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Un-blinded Rater | Week 6 | 3.47 units on a scale | Standard Deviation 1.58 |
| Dysport Injections | Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Un-blinded Rater | Week 12 | 3.26 units on a scale | Standard Deviation 1.47 |