Toxin Treatment for Amyotrophic Lateral Sclerosis (ALS) Related Sialorrhea (ALS-TOX)

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

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.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis; Sialorrhea
• Intervention / Treatment: Drug: Botox injection; Drug: Placebo injection

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Angers cedex 9, France, 49933
    • Département de Neurologie, Hôpital de l'Hôtel-Dieu, CHU d'Angers
  • Bron, France, 69677
    • Centre SLA, Groupement Hospitalier Est, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon
  • Caen cedex 9, France, 14033
    • Service de Neurologie Vastel, Hôpital Côte de Nacre, CHU de Caen
  • Clermont-Ferrand cedex 1, France, 63003
    • Service de Neurologie, Hôpital Gabriel Montpied, CHU de Clermont-Ferrand
  • Lille, France, 59037
    • Centre SLA, Service de Neurologie A et pathologies du mouvement, Hôpital Roger Salengro, CHU de Lille
  • Limoges, France, 87042
    • Service de Neurologie, Hôpital Dupuytren, CHU de Limoges
  • Marseille cedex 5, France, 13385
    • Service de Neurologie, Hôpital de la Timone, CHU de Marseille
  • Nancy, France, 54035
    • Service de Neurologie, Hôpital Central, CHU de Nancy
  • Nice cedex 3, France, 06202
    • Centre de Référence maladies Neuromusculaires, Service de Médecine Physique et Réadaptation, Hôpital de l'Archet 1, CHU de Nice
  • Paris cedex 13, France, 75651
    • Fédération des Maladies du Système Nerveux, Groupement Hospitalier Pitié Salpêtrière, AP-HP
  • Saint-Etienne cedex 2, France, 42055
    • Service de Neurologie, CHU de Saint-Etienne
  • Strasbourg, France, 67091
    • Département de Neurologie, Hôpital de Hautepierre, CHRU de Strasbourg
  • Toulouse, France, 31059
    • Service d'Explorations Fonctionelles Neuro-Musculaires, Hôpital Rangueil, CHU de Toulouse

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Christophe VIAL, MD, Centre SLA, Groupement Hospitalier Est, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: March 9, 2012
• First Submitted That Met QC Criteria: March 12, 2012
• First Posted (Estimate): March 13, 2012

Study Record Updates

• Last Update Posted (Estimate): August 14, 2015
• Last Update Submitted That Met QC Criteria: August 13, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Amyotrophic lateral sclerosis; Sialorrhea; Botulinum toxin
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Stomatognathic Diseases; Mouth Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Salivary Gland Diseases; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sialorrhea
• Other Study ID Numbers: 2010.607/11