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CompletedNCT03453632EBToxUpdated Sep 21, 2026

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

A Phase 2/3 interventional study of Botulinic toxin and Placebo in Epidermolysis Bullosa Simplex, sponsored by University Hospital, Toulouse. Completed at 4 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-21.

Sponsored by University Hospital, Toulouse · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
18
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Epidermolysis Bullosa Simplex

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Keywords

  • Dermatology
  • Rare skin diseases
  • epidermolysis bullosa simplex
  • botulinic toxin
  • blisters
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
18 participants (actual)

Study arms

  • Experimental
    Botulinic toxin

    Injections of botulinic toxin (Dysport®, Allergan) 200 UI

    Drug: Botulinic toxin

  • Placebo comparator
    Placebo

    Injections of physiological serum

    Drug: Placebo

Interventions

  • DrugBotulinic toxin

    Clinical photographs of the soles Standardized anesthesia protocol (lidocaine, prilocaine on soles, cryo-spray, oral administration of paracetamol and only if necessary oxycodone and hydroxyzine). Cleaning and antiseptic on the soles Injections of botulinic toxin (200 UI) on right or left foot

    Also known as: Dysport® (experimental drug)

  • DrugPlacebo

    Clinical photographs of the soles Standardized anesthesia protocol (lidocaine, prilocaine on soles, cryo-spray, oral administration of paracetamol and only if necessary oxycodone and hydroxyzine). Cleaning and antiseptic on the soles Injections of physiological serum (200 UI) on right or left foot

    Also known as: physiological serum

05

What researchers measure

Primary outcomes

  1. 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

    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

    Time frame: at baseline vs month 3

Secondary outcomes

  1. Global clinical improvement on each foot assessed by a blinded centralized independent reviewer using photographs: IGA score (Improvement Global Assessment) for each foot

    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

    Time frame: at baseline vs month 6

  2. Global clinical improvement on each foot assessed by the investigator: IGA score (Improvement Global Assessment) assessed for each foot.

    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

    Time frame: at month1, month 3 and month 6 respectively vs baseline

  3. Efficacy assessment concerning the number of plantar lesions clinically observed by the investigator

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

    Time frame: at baseline, month 1, month 3 and month 6

  4. Efficacy assessment on each foot of the affected plantar skin surface (blisters, erosions, erythematous and edematous areas, crusts)

    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.

    Time frame: at baseline, month 1, month 3 and month 6

  5. Efficacy assessment by the patient himself, for each foot

    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)

    Time frame: at month 1, month 3, month 6 and month 9

  6. Plantar pain assessment by the patient himself, for each foot

    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).

    Time frame: at baseline, month 1, month 3 and month 6

  7. Immediate tolerance during injection :

    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

    Time frame: Day 0

  8. Mid-term and long-term tolerance

    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.

    Time frame: Day 0, month 1, month 3 and month 6 and month 9

06

Study locations

4 sites
  • University Hospital Bordeaux
    Bordeaux, 33000, France
  • University Hospital Nice
    Nice, 06000, France
  • Saint-Louis Hospital - APHP
    Paris, 75000, France
  • Hôpital Larrey - CHU Toulouse
    Toulouse, 31059, France
07

References and documents

Publications

  • 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. PubMed 24690439 ↗
  • Sprecher E. Epidermolysis bullosa simplex. Dermatol Clin. 2010 Jan;28(1):23-32. doi: 10.1016/j.det.2009.10.003. PubMed 19945613 ↗
  • 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. PubMed 18828848 ↗
  • 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. PubMed 19153338 ↗
  • 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. PubMed 24650374 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03453632
Lead sponsor
University Hospital, Toulouse
Responsible party
Sponsor
First posted
Mar 5, 2018
Start date
Jun 14, 2018
Primary completion
Jan 21, 2025
Completion
Jan 21, 2025
Last update
Sep 21, 2026

Study contacts

Juliette Mazereeuw-Hautier, MD
principal investigator · University Hospital, Toulouse

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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