Clinical trial NCT03453632: Injections of Botulinic Toxin in Plantar Lesions of Localized Epidermolysis Bullosa Simplex
Official title: Evaluation of the Efficacy of Injections of Botulinic Toxin in Plantar Lesions of Patients Suffering From Localized Epidermolysis Bullosa Simplex : Double Blind Randomized Controlled Study.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Epidermolysis Bullosa Simplex
Keywords: Dermatology
Rare skin diseases
epidermolysis bullosa simplex
botulinic toxin
blisters
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2018-03-05
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Each subject is his own witness, receiving the 2 treatments : left foot vs. right foot
Primary purpose: TREATMENT

Brief summary: The investigators hypothesize that palmar injections of botulinic toxin, via an inhibition of the sudation, would limit the occurrence of blisters in localized epidermolysis bullosa simplex (LEBS).

Detailed description: Epidermolysis bullosa is a group of rare genetic diseases characterized by the occurrence of blisters and erosions due to skin fragility. There are 4 different subgroups, based on the location of the skin cleavage area. The most frequent subgroup is the simplex form, consisting predominantly of the localized form (localized epidermolysis bullosa simplex: LEBS). The incidence of LEBS was estimated at between 1/318.000 and 1/35.000. The disease starts early in infancy by the occurrence of blisters and erosions located on soles, secondary to frictions during the walk. The phenomenon is worsened by heat and sudation. LEBS is due to mutations in keratin genes. Life expectancy in LEBS is normal but the quality of life is significantly impaired due to permanent skin pain and limitation of everyday activities (walking, sports). There is no effective or curative treatment. Patients must limit the frictions, protect the skin and use plasters in case of skin lesions.

Botulinic toxin has an agreement for the treatment of axillary hyperhidrosis and has been shown to be also effective on palms and soles. The efficacy of botulinic toxin in plantar lesions of LEBS has been reported in the literature (one case report and a short retrospective series of 6 patients) but there is no proper study.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of LEBS based on clinical symptoms and in some cases histological or molecular findings
* Palmar skin lesions: blisters and/or : erosions, edematous and erythematous lesions, crusts. 3 lesions per foot, as a minimum
* Similar clinical severity of skin lesions on both feet
* Patient with social security
* Written consent of the patient
* Patient able to understand the study's questionnaires

Exclusion Criteria:

* Patients with only one leg and a different number of toes on each foot.
* Known hypersensitivity to botulinic toxin or its excipients
* Current treatment with aminosides
* Myasthenia
* Swallowing difficulties
* Respiratory disorders
* Past medical history of dysphagia or pneumopathy of inhalation
* Known allergy or contraindications to lidocaine, prilocaine, paracetamol or nitrous oxide
* Pregnancy (positive pregnancy test (β-HCG) for women of childbearing age, performed within the 2 days prior to the study. Breastfeeding.
* Contraception during 6 months from inclusion
* Mental or physical or judicial incapacity to fill the questionnaires
* Guardianship patients
* Skin infection on the soles at the time of the inclusion
* Skin lesions located on the soles, not related to LEBS (ie. post traumatic wound, wart)
* Patient suffering from dishydrosis
* Botulinic toxin injections in the previous 6 months
* Inclusion in another study in the previous 2 months

Primary outcomes:
measure: Global clinical improvement on each foot assessed by a blinded centralized independent reviewer using photographs, at M3 vs.baseline: IGA score (Improvement Global Assessment) assessed for each foot
timeFrame: at baseline vs month 3
Secondary outcomes:
measure: Global clinical improvement on each foot assessed by a blinded centralized independent reviewer using photographs: IGA score (Improvement Global Assessment) for each foot
timeFrame: at baseline vs month 6
measure: Global clinical improvement on each foot assessed by the investigator: IGA score (Improvement Global Assessment) assessed for each foot.
timeFrame: at month1, month 3 and month 6 respectively vs baseline
measure: Efficacy assessment concerning the number of plantar lesions clinically observed by the investigator
timeFrame: at baseline, month 1, month 3 and month 6
measure: Efficacy assessment on each foot of the affected plantar skin surface (blisters, erosions, erythematous and edematous areas, crusts)
timeFrame: at baseline, month 1, month 3 and month 6
measure: Efficacy assessment by the patient himself, for each foot
timeFrame: at month 1, month 3, month 6 and month 9
measure: Plantar pain assessment by the patient himself, for each foot
timeFrame: at baseline, month 1, month 3 and month 6
measure: Immediate tolerance during injection :
timeFrame: Day 0
measure: Mid-term and long-term tolerance
timeFrame: Day 0, month 1, month 3 and month 6 and month 9
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: University Hospital Bordeaux
city: Nice
country: France
facility: University Hospital Nice
city: Paris
country: France
facility: Saint-Louis Hospital - APHP
city: Toulouse
country: France
facility: Hôpital Larrey - CHU Toulouse
Study officials:
affiliation: University Hospital, Toulouse
name: Juliette Mazereeuw-Hautier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fine JD, Bruckner-Tuderman L, Eady RA, Bauer EA, Bauer JW, Has C, Heagerty A, Hintner H, Hovnanian A, Jonkman MF, Leigh I, Marinkovich MP, Martinez AE, McGrath JA, Mellerio JE, Moss C, Murrell DF, Shimizu H, Uitto J, Woodley D, Zambruno G. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014 Jun;70(6):1103-26. doi: 10.1016/j.jaad.2014.01.903. Epub 2014 Mar 29.
citation: Sprecher E. Epidermolysis bullosa simplex. Dermatol Clin. 2010 Jan;28(1):23-32. doi: 10.1016/j.det.2009.10.003.
citation: Langan SM, Williams HC. A systematic review of randomized controlled trials of treatments for inherited forms of epidermolysis bullosa. Clin Exp Dermatol. 2009 Jan;34(1):20-5. doi: 10.1111/j.1365-2230.2008.02789.x. Epub 2008 Sep 25.
citation: Abitbol RJ, Zhou LH. Treatment of epidermolysis bullosa simplex, Weber-Cockayne type, with botulinum toxin type A. Arch Dermatol. 2009 Jan;145(1):13-5. doi: 10.1001/archdermatol.2008.546. No abstract available.
citation: Schwieger-Briel A, Chakkittakandiyil A, Lara-Corrales I, Aujla N, Lane AT, Lucky AW, Bruckner AL, Pope E. Instrument for scoring clinical outcome of research for epidermolysis bullosa: a consensus-generated clinical research tool. Pediatr Dermatol. 2015 Jan-Feb;32(1):41-52. doi: 10.1111/pde.12317. Epub 2014 Mar 20.