Incobotulinum Toxin A for Sialorrhea in Parkinson's Disease (PD)/Parkinsonism and Amyotrophic Lateral Sclerosis (ALS) (Xeomin)

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

The purpose of this study is to evaluate the safety and efficacy of Incobotulinum Toxin A (Xeomin®) injections into the parotid and submandibular glands in patients with Parkinson's Disease/Parkinsonism and Amyotrophic Lateral Sclerosis (ALS) with troublesome sialorrhea.

Study Overview

• Status: Withdrawn
• Conditions: Parkinson Disease; Amyotrophic Lateral Sclerosis
• 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 ALS-FRS 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
• 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: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Hypothesis: Xeomin® injections into the parotid and submandibular glands are safe and effective in the treatment of troublesome sialorrhea in patients with PD/Parkinsonism and ALS.

Inclusion criteria are as follows:

For ALS: 1. Patients diagnosed with ALS by el-Escorial Criteria, ages 20-80 with troublesome sialorrhea as defined below**.

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**.

**Troublesome sialorrhea is defined as grade 3 or more (grade 3 is marked excess of saliva with some drooling) or more on the UPDRS Part 2 Sialorrhea grading scale:[33] (Appendix 1)

For both groups:

1. Swallowing function: FOIS scale* 5 or greater (see appendix 1 for scale)
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 both PD and ALS:

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: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xeomin Injections; Fifteen units (0.15 ml) of incobotulinum toxin A injected into each parotid gland and 20 units (0.2 ml) to each submandibular gland for a total dose of 70 units using anatomical landmarks for ALS Twenty units (0.2ml) 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 for PD/parkinsonism	Drug: Incobotulinum Toxin A; Xeomin 70-100 units injected in the parotid and submandibular glands of subjects; Other Names: Xeomin
Placebo Comparator: Placebo; 0.15 ml sterile 0.9% saline injected into each parotid gland and 0.2 ml to each submandibular gland using anatomical landmarks for ALS 0.2ml injected into each parotid gland and 0.3 ml to each submandibular gland using anatomical landmarks for PD/parkinsonism	Drug: placebo; Sterile preservative free 0.9% saline; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in objectively measured salivary volume between baseline and one month post-injection in the Xeomin group as compared to placebo	7 months

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Merz Pharmaceuticals
• Investigators: Principal Investigator: Pushpa Narayanaswami, ME, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: March 26, 2012
• First Submitted That Met QC Criteria: March 27, 2012
• First Posted (Estimate): March 28, 2012

Study Record Updates

• Last Update Posted (Estimate): February 7, 2017
• Last Update Submitted That Met QC Criteria: February 3, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: ALS; PD
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Stomatognathic Diseases; Mouth Diseases; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Salivary Gland Diseases; Sclerosis; Parkinson Disease; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Parkinsonian Disorders; Sialorrhea
• Other Study ID Numbers: 2011P000304

Plan for Individual participant data (IPD)

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