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

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

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.

Study Overview

• Status: Completed
• Conditions: Sialorrhea
• Intervention / Treatment: Drug: Incobotulinum Toxin A; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Incobotulinum Toxin A; 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; Other Names: Xeomin
Placebo Comparator: 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 .	Drug: 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 .; Other Names: Saline

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Investigators: Principal Investigator: Pushpa Narayanaswami, MD, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: July 25, 2012
• First Submitted That Met QC Criteria: July 27, 2012
• First Posted (Estimate): July 30, 2012

Study Record Updates

• Last Update Posted (Actual): March 14, 2017
• Last Update Submitted That Met QC Criteria: February 3, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: PD
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stomatognathic Diseases; Mouth Diseases; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Salivary Gland Diseases; Parkinson Disease; Parkinsonian Disorders; Sialorrhea
• Other Study ID Numbers: 2011P00304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No