Investigation of the Efficacy and Safety of IncobotulinumtoxinA (Xeomin) in Parkinson's Tremor: A Customized Approach

Study Overview
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Brief Summary
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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
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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.

Official Title
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Investigation of the Efficacy and Safety of IncobotulinumtoxinA (Xeomin) in Parkinson's Disease Tremor: A Customized Approach

Conditions
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Tremor, Parkinson

Intervention / Treatment
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* Drug: incobotulinumtoxinA
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria. Age more than 18 years Both sexes all races/ethnic groups. 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. Subjects who are able to read, speak, and understand English. Exclusion Criteria. Existing significant acute medical condition (i.e. cardiovascular, endocrine, hematologic, neoplastic, infectious, or autoimmune disorders) or significant swallowing or breathing difficulties. Pregnancy or planned pregnancy (determined by urine pregnancy test). Active breast feeding. Enrollment in any clinical trial (currently or within the past 3 months) in which treatments are imposed by a protocol. Any subject for whom botulinum toxin treatment would be contraindicated; known allergy or sensitivity to medication. Subjects who are younger than 18 years of age. Neuromuscular-junction disorders. Evidence of acute pathology in neuro-imaging. Axis I diagnosis determined by a neurologist or psychiatrist. Use of Anesthetic medications within two weeks and corticosteroid injections within 4 weeks of enrollment. Those who received botulinum toxin injections in the past 4 months.

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Placebo, then Xeomin<br>Subjects randomized to receive the placebo ( saline) will receive an equivalent volume as the active study drug (1cc). The injections will be into -10 hand and forearm muscles. A series of rating scale and an examination will take place prior to treatment and at 4 and 8 weeks post treatment. The subject will then cross over to an Active Intervention arm to receive incobotulinumtoxinA which will be injected in the same pattern as the saline. | Drug: incobotulinumtoxinA<br>* 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.<br>* Other names: Xeomin;Drug: Saline<br>* same volume as injected for incobotulinum toxin A into forearm muscles under EMG guidance.<br>* Other names: Placebo;|
| Active Comparator: Xeomin, then Placebo<br>Subjects will all receive injections with incobotulinumtoxinA injections, 100unit/cc into 6-10 muscles of the forearm. A series of rating scale and an examination will take place prior to treatment and at 4 and 8 weeks post treatment. These subjects will then cross over and receive placebo ( saline) in the same distribution as their second treatment. | Drug: incobotulinumtoxinA<br>* 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.<br>* Other names: Xeomin;Drug: Saline<br>* same volume as injected for incobotulinum toxin A into forearm muscles under EMG guidance.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 weeks | 
| 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 . | 4 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tremor, Parkinson, botulinum, Xeomin