Evaluation of the Efficacy of the Injection of Botulinum Toxin A vs Scopolamine Patches in the Treatment of Drooling in Children With Cerebral Palsy

Cerebral Palsy Clinical Trial

— TOXSIALO  

Official title:

Evaluation of the Long-term Efficacy of the Injection of Botulinum Toxin A Into the Salivary Glands Versus Scopolamine Patches in the Treatment of Drooling in Children Over 4 Years Old With Cerebral Palsy.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03616067
• Other study ID #: 69HCL18_0235
• Status: Recruiting
• Phase: Phase 3
• Start date: April 27, 2022
• Est. completion date: August 2025

Study information

• Verified date: April 2022
• Source: Hospices Civils de Lyon
• Contact: Karine POYAU, PhD
• Phone: 33 472 11 53 81
• Email: karine.poyau[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cerebral palsy is the first cause of motor disability in developed countries. It is associated with altered motor function but also with mental, sensorial and behavior deficiencies. Drooling frequently occurs in children with cerebral palsy (37 to 58%). It causes multiple medical and social complications which can all increase disability and reduce quality of life for the patients and their family. Drooling treatments are various and includes orofacial rehabilitations, anticholinergic medications, botulinum toxin A and B salivary gland injections. Surgeries could also be used, but their benefits are often outweighed by the risk.

• Orofacial rehabilitation is firstly recommended, even if few studies evaluated its efficacy.

• Medication by Scopoderm®, a cutaneous anticholinergic drug, is frequently used in spite of frequent side effects and a lack of evidence regarding efficacy.

• Botulinum toxin salivary gland injections (Botox®) were shown to be effective in reducing the severity of drooling consequences for the patient quality of life up to 12 months after the injections (Reid 2008).

A recent survey carried showed that treatment by Botox® injection would be preferred by professional to Scopoderm® patch, because of better tolerance and efficacy, even if Scopoderm® remained more used by professionals (Chaleat-Valayer 2016). However, a Cochrane review (Walshe 2012) concluded that there is 1) no strong consensus regarding assessment or the timing of all treatments 2) not enough efficacy studies with high level of evidence, 3) mostly efficacy studies vs placebo or no intervention 4) a lack of long term treatment assessment 5) a lack of studies on the patient quality of life.

Our study will be a comparative randomized clinical trial with an active control arm. The hypothesis is that therapeutic treatment of drooling in children with cerebral palsy consisting of a standardized rehabilitation treatment associated with a botulinum toxin A injection (Botox®) in the salivary glands is more effective than the same rehabilitation treatment associated with a treatment by scopolamine patches (Scopoderm®).

The main outcome will be assessed 15 months after initiation of treatment to evaluate long-term effectiveness. Patients from both arms of the trial will received rehabilitation, in order to compare treatment efficacy as it is done in real conditions of treatment. The efficacy of the treatment will be assessed on the impact of the drooling perceived by the patients and their family rather than on the measure of salivary production, as recommended (Walshe 2012).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: August 2025
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 18 Years

Eligibility

Inclusion Criteria:

• Aged 4 to 18 years old,

• Cerebral palsy with pathological drooling,

• Significant impact of drooling on the children (DIS score =40),

• Affiliated or beneficiary of a social security scheme,

• At least one of the parents understanding and speaking French,

• Written consent form signed by both parents

Exclusion Criteria:

• Previous history of surgery for drooling,

• Injection of botulinum toxin (all locations) in the 3 months prior to the inclusion,

• Treatment by scopolamine patch (Scopoderm®) or other anticholinergic (Artane®, etc.) in the month prior to inclusion,

• Contraindication to the anesthetic or sedation,

• Contraindication to one of the treatments studied (glaucoma, myastenia),

• Swallowing disorder (to saliva) or absence of spontaneous swallowing reflex not investigated by nasoscopy

• On-going or programmed orthodontic treatment over the study period.

• Untreated oro-mandibular dystonia (isolated lingual dystonia accepted)

• Untreated bruxism

• Untreated clinical gastro esophageal reflux

• Untreated dental inflammatory condition (dental caries, gingivitis…)

Related Conditions & MeSH terms

• Cerebral Palsy
• Sialorrhea

Intervention

Drug:
• Botox® injection
Botox® injection in salivary glands will be performed one month after inclusion. It will be performed with one injection point per gland (parotids and submandibulars)
• Scopoderm® patches arm
Scopoderm® patches will be initiated one month after inclusion. The patches will be renewed every 3 days, alternating behind each ear.

Locations

Country	Name	City	State
France	CHU d'Angers	Angers
France	CHU-Bordeaux	Bordeaux
France	Hôpital Femme Mère Enfant - HCL	Bron
France	CHU- Estaing	Clermont-Ferrand
France	CHU-Grenoble	Grenoble
France	Centre Médico-Chirurgical de Réadaptation des Massues	Lyon
France	AP-HM	Marseille
France	APFESEAN Nantes	Nantes
France	CHU-Nimes	Nîmes
France	Centre médico- infantile	Romagnat
France	Hôpitaux de Saint-Maurice	Saint-Maurice

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	Drooling Impact Scale (DIS scale)	The DIS scale is a questionnaire of 10 questions with a score of 100 points which will be completed by the patient's entourage (family and/or caregivers). This scale has a good validity and sensitivity to changes in the context of the evaluation of the drooling in children with CP, with a score difference of 10 points considered as clinical significant.	after 15 months of treatment
Secondary	DIS scale	The DIS scale is a questionnaire of 10 questions with a score of 100 points which will be completed by the patient's entourage (family and/or caregivers). This scale has a good validity and sensitivity to changes in the context of the evaluation of the drooling in children with CP, with a score difference of 10 points considered as clinical significant	at 1, 3, 6, 9 and 12 months of treatment
Secondary	Drooling severity	average number of bibs used per day per patient	at 1, 3, 6, 9, 12 and 15 months of treatment
Secondary	Clinical complications of the drooling	The number of hospitalizations for pulmonary infections and the average number of prescriptions for antibiotic treatment linked to bronchial secondary infection.	at 1, 3, 6, 9, 12 and 15 months of treatment