Sialorrhea
Conditions
Keywords
PD
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.
Interventions
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
DRUGPlacebo
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 .
Sponsors
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Countries
United States
Participant flow
Recruitment details
Subjects with Parkinson's disease/ parkinsonism with troublesome sialorrhea were recruited from the Movement Disorders clinic at Beth Israel Deaconess Medical Center, Boston, and by providing information to neurologists around the Boston area. Ten subjects were recruited between 9/5/2012 and 2/26/2014. The last study visit was completed on 9/5/14
Pre-assignment details
17 subjects were assessed; 7 were excluded because they did not meet study criteria. This was a cross over study; all subjects received both placebo and Incobotulinum toxin injections and were followed up for 3 months after each injection. Washout period was 1-2 months, saliva weight had to be ≥ (baseline- 0.5 SD), to receive the second injection
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants who received either Placebo, 1ml of preservative free sterile 0.9% saline, injected into the parotid (0.2 ml each) and submandibular ( 0.3 ml each), or Incobotulinum Toxin A 100 units, 20 units (0.2 ml) of Inco-A were injected into each parotid gland and 30 units (0.3 ml) to each submandibular gland using anatomical landmarks | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 68.1 years STANDARD_DEVIATION 9.7 |
| DFSS | 6 units on a scale |
| Region of Enrollment United States | 9 participants |
| saliva weight | 2.13 gms STANDARD_DEVIATION 4.19 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 6 Participants |
| UPDRS | 8.4 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 9 | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 |
Outcome results
Primary
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.
Time frame: baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Objectively Measured Percentage Salivary Weight | -7 percentage change from baseline | Standard Deviation 121 |
| Incobotulinum Toxin A | Objectively Measured Percentage Salivary Weight | -67 percentage change from baseline | Standard Deviation 239 |
95% CI: [-50.8, 6.2]
Primary
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.
Time frame: baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Objectively Measured Salivary Weight | -0.07 gm | Standard Deviation 1.21 |
| Incobotulinum Toxin A | Objectively Measured Salivary Weight | -0.68 gm | Standard Deviation 2.4 |
Comparison: Based on the primary outcome measure of mean reduction in saliva weight at 1 month post Inco-A /placebo as compared to baseline, using paired t-test with a two-sided nominal significance (alpha) of 0.05, assuming a correlation of 0.5 between observations, a sample size of 10 pairs has a power of 0.803 to detect a 50% difference in salivary weight.95% CI: [-0.71, 0.32]
Secondary
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 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
Time frame: baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Drooling Frequency and Severity Scale (DFSS) Scores | -1 units on a scale | Standard Deviation 1.41 |
| Incobotulinum Toxin A | Change in Drooling Frequency and Severity Scale (DFSS) Scores | -0.67 units on a scale | Standard Deviation 0.7 |
95% CI: [-1.16, 0.69]
Secondary
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
Time frame: between baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Response, Defined as Subjects With ≥ 20% Reduction in Saliva Volume. | 3 participants |
| Incobotulinum Toxin A | Number of Participants With Response, Defined as Subjects With ≥ 20% Reduction in Saliva Volume. | 2 participants |
95% CI: [-0.46, 0.28]
Secondary
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.
Time frame: baseline and one month post-injection in the Incobotulinum toxin A period compared to the placebo period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Response, Defined as Subjects With ≥ 2 Point Improvement in the DFSS Scores. | 2 participants |
| Incobotulinum Toxin A | Number of Participants With Response, Defined as Subjects With ≥ 2 Point Improvement in the DFSS Scores. | 1 participants |
95% CI: [-0.633, 0.071]