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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Hospices Civils de Lyon
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT01551940
First received: March 9, 2012
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Sialorrhea
Amyotrophic Lateral Sclerosis
Drug: Botox injection
Drug: Placebo injection
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Evaluation of Efficacy of Botulinum Toxin Type A in the Treatment of Sialorrhea in the Patient Affected by Amyotrophic Lateral Sclerosis (ALS)

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • Improvement of the functional embarrassment provoked by sialorrhea [ Time Frame: 1 month after the injection ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • Decrease of the salivary secretion rate and a decrease of the embarrassment for the main caregiver [ Time Frame: 1 month after the injection ] [ Designated as safety issue: No ]
    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.

  • Improvement of the value of the hypersalivation item in ALSFRS-R scale [ Time Frame: 1 month after the injection ] [ Designated as safety issue: No ]
    Demonstrate, one month after the injection of botulinum toxin type A, an improvement of the value of the hypersalivation item in ALSFRS-R scale.

  • Decrease of the score of severity and frequency of the drooling rating scale [ Time Frame: 1 month after the injection ] [ Designated as safety issue: No ]
    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

  • Decrease of the cotton roll weight [ Time Frame: 1 month after the injection ] [ Designated as safety issue: No ]

    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.


  • Decrease of the number of paper handkerchiefs used [ Time Frame: 1 month after the injection ] [ Designated as safety issue: No ]
    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.

  • Modification of the speech evaluation [ Time Frame: 1 month after the injection ] [ Designated as safety issue: No ]
    Demonstrate, one month after the injection of botulinum toxin typeA, a modification of the speech evaluation (evaluation realized by speech evaluator)

  • Improvement of the quality of life [ Time Frame: 1 month after the injection ] [ Designated as safety issue: No ]
    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

  • Description of patient cohort after the first injection [ Time Frame: 6 months after the injection ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 90
Study Start Date: February 2012
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Botox
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
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01551940

Contacts
Contact: Nadia Vandenberghe, MD 472 11 90 65 ext +33 nadia.vandenberghe@chu-lyon.fr
Contact: Sylvie Bin, MD 472 11 54 38 ext +33 sylvie.bin@chu-lyon.fr

Locations
France
Département de Neurologie, Hôpital de l'Hôtel-Dieu, CHU d'Angers Recruiting
Angers cedex 9, France, 49933
Contact: Julien CASSEREAU, MD         
Principal Investigator: Julien CASSEREAU, MD         
Centre SLA, Groupement Hospitalier Est, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon Recruiting
Bron, France, 69677
Contact: Nadia Vandenberghe, MD    472 11 90 65 ext +33    nadia.vandenberghe@chu-lyon.fr   
Principal Investigator: Nadia Vandenberghe, MD         
Service de Neurologie Vastel, Hôpital Côte de Nacre, CHU de Caen Recruiting
Caen cedex 9, France, 14033
Contact: Fausto VIADER, MD, PhD         
Principal Investigator: Fausto VIADER, MD, PhD         
Service de Neurologie, Hôpital Gabriel Montpied, CHU de Clermont-Ferrand Recruiting
Clermont-Ferrand cedex 1, France, 63003
Contact: Pierre CLAVELOU, MD, PhD         
Principal Investigator: Pierre CLAVELOU, MD, PhD         
Centre SLA, Service de Neurologie A et pathologies du mouvement, Hôpital Roger Salengro, CHU de Lille Recruiting
Lille, France, 59037
Contact: Véronique DANEL - BRUNAUD, MD         
Principal Investigator: Véronique DANEL - BRUNAUD, MD         
Service de Neurologie, Hôpital Dupuytren, CHU de Limoges Recruiting
Limoges, France, 87042
Contact: Philippe COURATIER, MD, PhD         
Principal Investigator: Philippe COURATIER, MD, PhD         
Service de Neurologie, Hôpital de la Timone, CHU de Marseille Recruiting
Marseille cedex 5, France, 13385
Contact: Annie VERSCHUEREN, MD, PhD         
Principal Investigator: Annie VERSCHUEREN, MD, PhD         
Service de Neurologie, Hôpital Central, CHU de Nancy Recruiting
Nancy, France, 54035
Contact: Sophie PITTION VOUYOVITCH, MD         
Principal Investigator: Sophie PITTION VOUYOVITCH, MD         
Centre de Référence maladies Neuromusculaires, Service de Médecine Physique et Réadaptation, Hôpital de l'Archet 1, CHU de Nice Recruiting
Nice cedex 3, France, 06202
Contact: Claude DESNUELLE, MD, PhD         
Principal Investigator: Claude DESNUELLE, MD, PhD         
Fédération des Maladies du Système Nerveux, Groupement Hospitalier Pitié Salpêtrière, AP-HP Recruiting
Paris cedex 13, France, 75651
Contact: François SALACHAS, MD         
Principal Investigator: François SALACHAS, MD         
Service de Neurologie, CHU de Saint-Etienne Recruiting
Saint-Etienne cedex 2, France, 42055
Contact: Jean-Christophe ANTOINE, MD, PhD         
Principal Investigator: Jean-Christophe ANTOINE, MD, PhD         
Département de Neurologie, Hôpital de Hautepierre, CHRU de Strasbourg Recruiting
Strasbourg, France, 67091
Contact: Marie-Céline FLEURY, MD         
Principal Investigator: Marie-Céline FLEURY, MD         
Service d'Explorations Fonctionelles Neuro-Musculaires, Hôpital Rangueil, CHU de Toulouse Recruiting
Toulouse, France, 31059
Contact: Marie-Christine ARNE-BES, MD         
Principal Investigator: Marie-Christine ARNE-BES, MD         
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Principal Investigator: Nadia Vandenberghe, MD Centre SLA, Groupement Hospitalier Est, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon
  More Information

No publications provided

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT01551940     History of Changes
Other Study ID Numbers: 2010.607/11
Study First Received: March 9, 2012
Last Updated: January 14, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Hospices Civils de Lyon:
Sialorrhea
Amyotrophic lateral sclerosis
Botulinum toxin

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Sialorrhea
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Botulinum Toxins
Botulinum Toxins, Type A
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014