Parkinson, Tremor
Conditions
Keywords
Tremor, Parkinson, botulinum, Xeomin
Brief summary
The scientific aim of this study is to investigate the efficacy and safety of incobotulinumtoxinA (Xeomin-Merz Pharmaceuticals) in the tremor of Parkinsons disease. Our hypothesis is that injection of Xeomin into the muscles of arm, forearm and hand decreases the tremor amplitude and frequency leading to improvement of the patients function.
Detailed description
This is an investigator initiated, randomized, double blind, placebo controlled, cross over study which is supported by Merz pharmaceuticals. Patients with Parkinsons disease (at Yale Neurology and Movement disorders clinics) will be approached by the members of the research team (PI and sub-investigators) to see if they meet inclusion and exclusion criteria and wish to participate in the study. If eligible and consented to participate in the study, there will be a series of questionaires, examinations and treatment sessions.
Interventions
Subjects randomized to the active drug intervention arm will receive incobotulinumtoxinA (Xeomin). A series of rating scales and examinations will take place prior to treatment and for 24 weeks after treatment. At 12 weeks the subjects will cross over to the placebo (saline) arm.
DRUGSaline
same volume as injected for incobotulinum toxin A into forearm muscles under EMG guidance.
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
. 1. Age more than 18 years 2. Both sexes 3. all races/ethnic groups. 4. Meeting the clinical diagnosis of Parkinson's disease with presence of moderate to severe Parkinson tremor that is refractory to standard medical treatments and which limits the patients functionality and/or poses significant discomfort. 5. Subjects who are able to read, speak, and understand English.
Exclusion criteria
. 1. Existing significant acute medical condition (i.e. cardiovascular, endocrine, hematologic, neoplastic, infectious, or autoimmune disorders) or significant swallowing or breathing difficulties. 2. Pregnancy or planned pregnancy (determined by urine pregnancy test). 3. Active breast feeding. 4. Enrollment in any clinical trial (currently or within the past 3 months) in which treatments are imposed by a protocol. 5. Any subject for whom botulinum toxin treatment would be contraindicated; known allergy or sensitivity to medication. 6. Subjects who are younger than 18 years of age. Neuromuscular-junction disorders. 7. Evidence of acute pathology in neuro-imaging. 8. Axis I diagnosis determined by a neurologist or psychiatrist. 9. Use of Anesthetic medications within two weeks and corticosteroid injections within 4 weeks of enrollment. 10. Those who received botulinum toxin injections in the past 4 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unified Parkinsons Disease Rating Scale (UPDRS) Tremor Scale | 4 weeks | The primary outcome measure in this protocol is significant improvement of tremor (equal or over 2 grade improvement) of the Unified Parkinson's Disease Rating Scale 4 weeks after Xeomin injection. The score is 0 to 4 , ) being no tremor and 4 severe tremor. The higher the score, the more severe the tremor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Whose Patient Global Impression of Change (PGIC) Improved | 4 weeks | The PGIC is a 7 point scale that requires the clinician to assess how much the patient's pain has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: No change (or condition has gotten worse) (1) Almost the same, hardly any change at all (2) A little better, but no noticeable change (3) Somewhat better, but the change has not made any real difference (4) Moderately better, and a slight but noticeable change (5) Better and a definite improvement that has made a real and worthwhile difference (6) A great deal better and a considerable improvement that has made all the difference (7)improved This outcome is number of patients who chose a 6 or above on the PGIC 6 weeks after treatment. |
| Patients With Significant Improvement in Unified Parkinsons Disease Rating Tremor Scale | 4 Weeks | This scale measures the amplitude of the tremor. For instance tremor of more than 4cm oscillation is grade 4. UPDRS tremor scale is 0-4 , 4 being severe tremor. Significant improvement for this protocol considered two grades of improvement . |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All participants included in this crossover design. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Lost to Follow-up | 2 | 0 |
| Second Intervention | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 61.7 years |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 33 | 3 / 33 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Unified Parkinsons Disease Rating Scale (UPDRS) Tremor Scale
The primary outcome measure in this protocol is significant improvement of tremor (equal or over 2 grade improvement) of the Unified Parkinson's Disease Rating Scale 4 weeks after Xeomin injection. The score is 0 to 4 , ) being no tremor and 4 severe tremor. The higher the score, the more severe the tremor.
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo, Saline | Unified Parkinsons Disease Rating Scale (UPDRS) Tremor Scale | 0 participants |
| incobotulinumtoxinA, Xeomin | Unified Parkinsons Disease Rating Scale (UPDRS) Tremor Scale | 8 participants |
p-value: 0.0007Fisher Exact
Secondary
Number of Patients Whose Patient Global Impression of Change (PGIC) Improved
The PGIC is a 7 point scale that requires the clinician to assess how much the patient's pain has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: No change (or condition has gotten worse) (1) Almost the same, hardly any change at all (2) A little better, but no noticeable change (3) Somewhat better, but the change has not made any real difference (4) Moderately better, and a slight but noticeable change (5) Better and a definite improvement that has made a real and worthwhile difference (6) A great deal better and a considerable improvement that has made all the difference (7)improved This outcome is number of patients who chose a 6 or above on the PGIC 6 weeks after treatment.
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo, Saline | Number of Patients Whose Patient Global Impression of Change (PGIC) Improved | 0 participants |
| incobotulinumtoxinA, Xeomin | Number of Patients Whose Patient Global Impression of Change (PGIC) Improved | 10 participants |
p-value: 0.0008Fisher Exact
Secondary
Patients With Significant Improvement in Unified Parkinsons Disease Rating Tremor Scale
This scale measures the amplitude of the tremor. For instance tremor of more than 4cm oscillation is grade 4. UPDRS tremor scale is 0-4 , 4 being severe tremor. Significant improvement for this protocol considered two grades of improvement .
Time frame: 4 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo, Saline | Patients With Significant Improvement in Unified Parkinsons Disease Rating Tremor Scale | 0 participants |
| incobotulinumtoxinA, Xeomin | Patients With Significant Improvement in Unified Parkinsons Disease Rating Tremor Scale | 8 participants |
p-value: 0.0105Fisher Exact