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

NCT ID: NCT03453632

Last Updated: 2023-08-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-14
• Study Completion Date: 2023-12-31

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.

Conditions

Epidermolysis Bullosa Simplex

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Botulinic toxin

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

Group Type: EXPERIMENTAL

Botulinic toxin

Intervention Type: DRUG

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

Placebo

Injections of physiological serum

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Botulinic 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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Dysport® (experimental drug); physiological serum

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Juliette Mazereeuw-Hautier, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

University Hospital Bordeaux

Bordeaux, , France

Site Status: RECRUITING

University Hospital Nice

Nice, , France

Site Status: RECRUITING

Saint-Louis Hospital - APHP

Paris, , France

Site Status: RECRUITING

Hôpital Larrey - CHU Toulouse

Toulouse, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Juliette Mazereeuw-Hautier, MD

Role: CONTACT

mazereeuw-hautier.j@chu-toulouse.fr

5 67 77 81 41 ext. 33

Isabelle DREYFUS, PharmD

Role: CONTACT

dreyfus.i@chu-toulouse.fr

5 67 77 81 10 ext. 33

Facility Contacts

Olivier COGREL, MD

Role: primary

Christine CHIAVERINI, MD

Role: primary

Emmanuel Bourrat, MD

Role: primary

Juliette Mazereeuw-Hautier, Pr

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 24650374 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24690439 (View on PubMed)

Sprecher E. Epidermolysis bullosa simplex. Dermatol Clin. 2010 Jan;28(1):23-32. doi: 10.1016/j.det.2009.10.003.

Reference Type: BACKGROUND

PMID: 19945613 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18828848 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19153338 (View on PubMed)

Other Identifiers

2017-002332-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RC31/16/8917

Identifier Type: -

Identifier Source: org_study_id