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Injections of Botulinic Toxin in Plantar Lesions of Localized Epidermolysis Bullosa Simplex

Phase 2
Recruiting
Conditions
Epidermolysis Bullosa Simplex
Interventions
Drug: Botulinic toxin
Drug: Placebo
Registration Number
NCT03453632
Lead Sponsor
University Hospital, Toulouse
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
25
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Botulinic toxinBotulinic toxinInjections of botulinic toxin (Dysport®, Allergan) 200 UI
PlaceboPlaceboInjections of physiological serum
Primary Outcome Measures
NameTimeMethod
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 footat baseline vs month 3

IGA score is a 5-point scale (range from 0 to 4): 0=no improvement or worsening / 1=minimal improvement / 2=moderate improvement / 3=significant improvement / 4=total disappearance

Secondary Outcome Measures
NameTimeMethod
Efficacy assessment concerning the number of plantar lesions clinically observed by the investigatorat baseline, month 1, month 3 and month 6

on each foot (erythematous and edematous areas, blisters, skin erosion, crusts)

Efficacy assessment on each foot of the affected plantar skin surface (blisters, erosions, erythematous and edematous areas, crusts)at baseline, month 1, month 3 and month 6

calculation of this affected surface by delimiting its contours on a standardized photography using "Image J" software = computerized assessment by a blinded centralized independent reviewer.

Efficacy assessment by the patient himself, for each footat month 1, month 3, month 6 and month 9

Global improvement assessed with a 5-point score (0=no improvement or worsening / 1=minimal improvement / 2=moderate improvement / 3=significant improvement / 4=total disappearance)

Immediate tolerance during injection :Day 0

Assessment performed by the patient of the pain felt during the act for each foot, using a 0 to 10 pain EVA scale (patient interview). Assessment performed by the investigator of local adverse events (for each foot) or general adverse events, during the injections

Mid-term and long-term toleranceDay 0, month 1, month 3 and month 6 and month 9

Assessment performed by the patient of local adverse events (for each foot) or general adverse events reported in the home patient's diary between the protocol visits (collected at month 1, month 3, month 6 and month 9). • Assessment performed by investigator of local adverse events (for each foot) or general adverse events, at D0 (at the end of/after the injections), M3 and M6.

Global clinical improvement on each foot assessed by a blinded centralized independent reviewer using photographs: IGA score (Improvement Global Assessment) for each footat baseline vs month 6

IGA score is a 5-point scale (range from 0 to 4): 0=no improvement or worsening / 1=minimal improvement / 2=moderate improvement / 3=significant improvement / 4=total disappearance

Global clinical improvement on each foot assessed by the investigator: IGA score (Improvement Global Assessment) assessed for each foot.at month1, month 3 and month 6 respectively vs baseline

IGA score is a 5-point scale (range from 0 to 4): 0=no improvement or worsening / 1=minimal improvement / 2=moderate improvement / 3=significant improvement / 4=total disappearance

Plantar pain assessment by the patient himself, for each footat baseline, month 1, month 3 and month 6

Plantar pain assessment , using a 0 to 10 pain EVA scale. To perform the assessment, patient is requested to be standing on one foot (assessment of pain felt for this foot using EVA scale) then, standing on the other foot (assessment of pain felt for this other foot using EVA scale).

Trial Locations

Locations (4)

Hôpital Larrey - CHU Toulouse

🇫🇷

Toulouse, France

University Hospital Bordeaux

🇫🇷

Bordeaux, France

University Hospital Nice

🇫🇷

Nice, France

Saint-Louis Hospital - APHP

🇫🇷

Paris, France

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