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

NCT ID: NCT01565395

Last Updated: 2017-02-07

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2013-07-31

Brief Summary

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.

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.

Conditions

Parkinson Disease; Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

Incobotulinum Toxin A

Intervention Type: DRUG

Xeomin 70-100 units injected in the parotid and submandibular glands of subjects

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Sterile preservative free 0.9% saline

Interventions

Incobotulinum Toxin A

Xeomin 70-100 units injected in the parotid and submandibular glands of subjects

Intervention Type: DRUG

placebo

Sterile preservative free 0.9% saline

Intervention Type: DRUG

Other Intervention Names

Xeomin; Saline

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merz Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Pushpa Narayanaswami

Associate Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pushpa Narayanaswami, ME

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

2011P000304

Identifier Type: -

Identifier Source: org_study_id