Incobotulinum Toxin A (Xeomin®) for Troublesome Sialorrhea in Parkinson's Disease (PD)/Parkinsonism

Study Overview
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Brief Summary
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This study is being conducted this study to determine whether injections of Xeomin®, a type of botulinum toxin into the glands that produce saliva (one pair just below and in front of the ear and the other just under the jaw line) are safe and effective to treat excessive saliva, or drooling in patients with Parkinson's Disease (PD)/parkinsonism.

Detailed Description
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Participants will be recruited if they have Parkinson's disease, Parkinsonism. Inclusion and exclusion criteria are summarized below. Participants will be screened at the first visit to make sure they are eligible for the trial. They will then undergo baseline testing including neurologic evaluation, questions to assess their memory and cognitive status and evaluation of their disease status using parts of the Unified Parkinsons's Disease Ratings Scale (UPDRS) that are routinely used to follow disease progression. They will be given a questionnaire to evaluate the severity of their drooling. Their saliva production will be measured by having them spit into a cup for 5 minutes, twice. At the first visit, after making sure they are eligible for the study and performing the baseline testing and procedures, they will be given either Xeomin or placebo (saline injections without medication) injections in the 4 glands that produce saliva. They will not know which injection they received. This visit will take about 2 hours. They will be followed up every month and asked about side effects, have neurologic evaluation and UPDRS testing and fill-in the questionnaire for drooling severity. Saliva volume will be measured as done at the first visit. At either Month 4 or 5, participants will receive the second injection. This will be a cross-over injection, i.e., if they received Xeomin at the first injection they will receive saline at the second and vice versa. Thus, all participants will receive the study medication Xeomin, either as the first injection or the second injection at 4 months or 5 months. The follow up after the second injection will be one monthly visit for 3 months, with similar evaluations as described above. The follow-up visit will take about 1 hour each.

Official Title
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Randomized Double Blind Placebo Controlled Cross-Over Study of Incobotulinum Toxin A (Xeomin®) for Troublesome Sialorrhea in Parkinson's Disease (PD)/Parkinsonism

Conditions
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Sialorrhea

Intervention / Treatment
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* Drug: Incobotulinum Toxin A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For PD/ Parkinsonism: 1. PD, Multiple Systems Atrophy (MSA), or Progressive Supranuclear Palsy (PSP) diagnosed by clinical criteria, ages 20-80 with troublesome sialorrhea as defined below**. Sialorrhea that patients or their families or treating physicians think is troublesome Swallowing function: Functional Oral Intake Scale (FOIS)* of 5 or greater If patients have been treated with other medications for sialorrhea earlier, they should be off the medications at least 4 weeks prior to the baseline evaluation. If they are on other medications for sialorrhea at the time of the baseline evaluation, the doses will be held stable throughout the period of the study. Women of child bearing age will need to be on a reliable method of birth control for the duration of the study. Exclusion Criteria: For PD: Current use of Coumadin Concurrent significant medical illness History of myasthenia gravis or Lambert-Eaton Syndrome Ongoing substance abuse History of unreliable follow-up Past use of Xeomin® or other botulinum toxin preparations Cognitive impairment, defined as a score ≤ 23/30 on the Mini Mental Status Exam

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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 |
| --- | --- |
| Experimental: Incobotulinum Toxin A<br>Twenty units (0.2 ml) of incobotulinum toxin A injected into each parotid gland and 30 units (0.3 ml) to each submandibular gland for a total dose of 100 units using anatomical landmarks | Drug: Incobotulinum Toxin A<br>* Twenty units (0.2 ml) of incobotulinum toxin A were injected into each parotid gland and 30 units (0.3 ml) to each submandibular gland for a total dose of 100 units using anatomical landmarks<br>* Other names: Xeomin;|
| Placebo Comparator: Placebo<br>Sterile, preservative free 0.9% saline, 1 ml, was used as placebo, and injected into the parotid (0.2 ml each) and submandibular (0.3ml each) glands . | Drug: Placebo<br>* Sterile, preservative free 0.9% saline, 1 ml, was used as placebo, and injected into the parotid (0.2 ml each) and submandibular (0.3ml each) glands .<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objectively Measured Salivary Weight | Change in saliva weight between baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period. | baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period | 
| Objectively Measured Percentage Salivary Weight | Percentage change in saliva weight between baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period. | baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Drooling Frequency and Severity Scale (DFSS) Scores | measured between baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period.Drooling Frequency and Severity Score. The Drooling Score equals the sum of the Severity and Frequency sub-scores. The range is 2-9, higher numbers represent worse drooling Drooling Severity Scale = Never drools, dry = Mild-drooling, only lips wet = Moderate- drool reaches the lips and chin = Severe- drool drips off chin & onto clothing = Profuse- drooling off the body and onto objects (furniture, books) Drooling Frequency Scale 1. = No drooling 2. = Occasionally drools 3. = Frequently drools 4. = Constant drooling | baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period | 
| Number of Participants With Response, Defined as Subjects With ≥ 2 Point Improvement in the DFSS Scores. | measured between baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period. | baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period | 
| Number of Participants With Response, Defined as Subjects With ≥ 20% Reduction in Saliva Volume. | measured between baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period | between baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD