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

Phase 2

Completed

Conditions: Sialorrhea

Interventions: Drug: Placebo
Drug: Incobotulinum Toxin A

Registration Number: NCT01653132

Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

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
  1. Swallowing function: Functional Oral Intake Scale (FOIS)* of 5 or greater
  2. 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.
  3. 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.
  4. 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:
1. Current use of Coumadin
2. Concurrent significant medical illness
3. History of myasthenia gravis or Lambert-Eaton Syndrome
4. Ongoing substance abuse
5. History of unreliable follow-up
6. Past use of Xeomin® or other botulinum toxin preparations
7. Cognitive impairment, defined as a score ≤ 23/30 on the Mini Mental Status Exam

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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 .
Incobotulinum Toxin A	Incobotulinum Toxin A	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Response, Defined as Subjects With ≥ 2 Point Improvement in the DFSS Scores.	baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period	measured between 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.	between baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period	measured between baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period
Change in Drooling Frequency and Severity Scale (DFSS) Scores	baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period	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 1. = Never drools, dry 2. = Mild-drooling, only lips wet 3. = Moderate- drool reaches the lips and chin 4. = Severe- drool drips off chin \& onto clothing 5. = 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