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Injections of Botulinic Toxin in Plantar Lesions of Localized Epidermolysis Bullosa Simplex (EBTox)

Primary Purpose

Epidermolysis Bullosa Simplex

Status

Recruiting

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Botulinic toxin

Placebo

About this trial

This is an interventional treatment trial for Epidermolysis Bullosa Simplex focused on measuring Dermatology, Rare skin diseases, epidermolysis bullosa simplex, botulinic toxin, blisters

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University Hospital BordeauxRecruiting
University Hospital NiceRecruiting
Saint-Louis Hospital - APHPRecruiting
Hôpital Larrey - CHU ToulouseRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Botulinic toxin

Placebo

Arm Description

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

Injections of physiological serum

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

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)

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 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)

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).

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

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.

Full Information

NCT ID

NCT03453632

First Posted

February 6, 2018

Last Updated

August 22, 2023

Sponsor

University Hospital, Toulouse

1. Study Identification

Unique Protocol Identification Number

NCT03453632

Brief Title

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

Acronym

EBTox

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

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 14, 2018 (Actual)

Primary Completion Date

September 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Toulouse

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epidermolysis Bullosa Simplex

Keywords

Dermatology, Rare skin diseases, epidermolysis bullosa simplex, botulinic toxin, blisters

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Crossover Assignment

Model Description

Each subject is his own witness, receiving the 2 treatments : left foot vs. right foot

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Botulinic toxin

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Injections of physiological serum

Intervention Type

Drug

Intervention Name(s)

Botulinic toxin

Other Intervention Name(s)

Dysport® (experimental drug)

Intervention Description

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

Intervention Name(s)

Placebo

Other Intervention Name(s)

physiological serum

Intervention Description

Primary Outcome Measure Information:

Title

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

Description

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 Outcome Measure Information:

Title

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

Description

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

Title

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

Description

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

Title

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

Description

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

Time Frame

at baseline, month 1, month 3 and month 6

Title

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

Description

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

Title

Efficacy assessment by the patient himself, for each foot

Description

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

Title

Plantar pain assessment by the patient himself, for each foot

Description

Time Frame

at baseline, month 1, month 3 and month 6

Title

Immediate tolerance during injection :

Description

Time Frame

Day 0

Title

Mid-term and long-term tolerance

Description

Time Frame

Day 0, month 1, month 3 and month 6 and month 9

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Juliette Mazereeuw-Hautier, MD

Phone

5 67 77 81 41

Ext

mazereeuw-hautier.j@chu-toulouse.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Isabelle DREYFUS, PharmD

Phone

5 67 77 81 10

Ext

dreyfus.i@chu-toulouse.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Juliette Mazereeuw-Hautier, MD

Organizational Affiliation

University Hospital, Toulouse

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Bordeaux

City

Bordeaux

ZIP/Postal Code

33000

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Olivier COGREL, MD

Facility Name

University Hospital Nice

City

Nice

ZIP/Postal Code

06000

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christine CHIAVERINI, MD

Facility Name

Saint-Louis Hospital - APHP

City

Paris

ZIP/Postal Code

75000

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Emmanuel Bourrat, MD

Facility Name

Hôpital Larrey - CHU Toulouse

City

Toulouse

ZIP/Postal Code

31059

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Juliette Mazereeuw-Hautier, Pr

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

24690439

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.

Results Reference

background

PubMed Identifier

19945613

Citation

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

Results Reference

background

PubMed Identifier

18828848

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.

Results Reference

background

PubMed Identifier

19153338

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.

Results Reference

background

PubMed Identifier

24650374

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.

Results Reference

background

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

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