Toxin Treatment for Amyotrophic Lateral Sclerosis (ALS) Related Sialorrhea

Study Overview
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Brief Summary
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Evaluation of the decrease of the secretion of saliva in patients with amyotrophic lateral sclerosis by a local ultrasound-guided bilateral injection of botulinum toxin type A in parotids and submandibular glands. The investigators want to demonstrate 1 month after the injection, by a multicenter French randomized double blind study, an improvement of at least 25 % of the functional embarrassment due to saliva, estimated with a visual analogue scale, a decrease of the quantity of saliva and a decrease of the embarrassment for the main caregiver.

Detailed Description
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The patient will benefit from an ultrasound guided injection of botulinum toxin A (Botox®) or placebo (NaCl 0.9 %) and will be followed up in consultation at 4, 12, 16 (if reinjection) and 24 weeks. He will be contacted by telephone in 2 and in 8 weeks (percentage of decrease of functional embarrassment, percentage of decrease of salivary secretion rate). He can be able to benefit in the open label phase of a botulinum toxin type A injection at the 12-week follow up if he estimates that first injection was not effective or if the efficiency of the first injection began to become blurred. After the 6 months of the study, the patient will benefit again from the usual follow-up as advised by the French consensus conference in November, 2005.

Official Title
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Evaluation of Efficacy of Botulinum Toxin Type A in the Treatment of Sialorrhea in the Patient Affected by Amyotrophic Lateral Sclerosis (ALS)

Conditions
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Sialorrhea, Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Botox injection
* Drug: Placebo injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Obtaining of a written consent after information Diagnosis of probable or certain ALS according to the El Escorial criteria of the World Federation and Neurology Committee on Neuromuscular Diseases Patient having a follow-up in an ALS center Sialorrhea with VAS functional embarrassment > or equal at 50/100. Patient beneficiary of Social Security regime Exclusion Criteria: Evolving disease associated with predictable survival < 1 month Patient having previously received an injection of botulinum toxin in the salivary glands Patient taking the other medical treatments for sialorrhea in the 7 days before the inclusion in the study (scopoderm, trihexyph'nidyle, atropine, ipatropium, amitriptyline, clomipramine, oxybutinine, diphenhydramine, beta-blockers) Patient having benefited from radiotherapy or from surgery on the salivary glands Behavioral problems, dementia or other psychiatric problems Myasthenia Known Pregnancy or absence of contraception recognized as effective, breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Botox<br>Botox injection : 100 UI of botulinum toxin type A (Botox®) diluted in 2.2 ml of NaCl 0.9 % | Drug: Botox injection<br>* Local ultrasound-guided bilateral injection of botulinum toxin type A in parotid (35 UI/gland) and submandibular (15 UI/gland) glands.<br>|
| Placebo Comparator: Placebo<br>Placebo injection : NaCl 0.9 % | Drug: Placebo injection<br>* A local ultrasound-guided bilateral injection of placebo (NaCl 0.9 %) in parotid (0.7 ml/gland) and submandibular (0.3 ml/gland) glands.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of the functional embarrassment provoked by sialorrhea | Demonstrate after the injection of botulinum toxin type A an improvement of at least 25 % of the functional embarrassment provoked by sialorrhea in the ALS patient, evaluated with a horizontal visual analogue scale (VAS). | 1 month after the injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease of the salivary secretion rate and a decrease of the embarrassment for the main caregiver | Demonstrate, one month after the injection of botulinum toxin type A, a decrease of the salivary secretion rate and a decrease of the embarrassment for the main caregiver by a horizontal visual analogue scale. | 1 month after the injection | 
| Improvement of the value of the hypersalivation item in ALSFRS-R scale | Demonstrate, one month after the injection of botulinum toxin type A, an improvement of the value of the hypersalivation item in ALSFRS-R scale. | 1 month after the injection | 
| Decrease of the score of severity and frequency of the drooling rating scale | Demonstrate, one month after the injection of botulinum toxin type A, a decrease of the score of severity and frequency of the drooling rating scale | 1 month after the injection | 
| Decrease of the cotton roll weight | Demonstrate, one month after the injection of botulinum toxin type A, a decrease of the cotton roll weight. Cotton rolls weight: production and quantity of saliva are verified by placing dental cotton rolls during 3 minutes in the mouth of the patient and by comparing the weight of rolls dry and soaked with saliva. | 1 month after the injection | 
| Decrease of the number of paper handkerchiefs used | Demonstrate, one month after the injection of botulinum toxin type A, a decrease of the number of paper handkerchiefs used. We ask the patient to count the number of handkerchiefs used a day. | 1 month after the injection | 
| Modification of the speech evaluation | Demonstrate, one month after the injection of botulinum toxin typeA, a modification of the speech evaluation (evaluation realized by speech evaluator) | 1 month after the injection | 
| Improvement of the quality of life | Demonstrate, one month after the injection of botulinum toxin type A, an improvement of the quality of life. Scale to estimate quality of life (ALSAQ-40), usually used with the patients affected by ALS | 1 month after the injection | 
| Description of patient cohort after the first injection | Describe cohort after the first injection: evolution of scores for every patient among Day0 and Month1, delay of appearance of the efficiency, the duration of effect of the treatment, the side effects, the modification of the consistency of the saliva and the possible necessity for re-injecting the patient at 3 months of follow-up. | 6 months after the injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sialorrhea, Amyotrophic lateral sclerosis, Botulinum toxin