Toxin Treatment for Amyotrophic Lateral Sclerosis (ALS) Related Sialorrhea

Amyotrophic Lateral Sclerosis Clinical Trial

— ALS-TOX  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01551940
• Other study ID #: 2010.607/11
• Status: Completed
• Phase: Phase 2
• First received: March 9, 2012
• Last updated: August 13, 2015
• Start date: February 2012
• Est. completion date: March 2014

Study information

• Verified date: August 2015
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis
• Sialorrhea

Intervention

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 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No