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

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ClinicalTrials.gov Identifier: NCT03453632
Recruitment Status : Recruiting
First Posted : March 5, 2018
Last Update Posted : December 20, 2018
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Epidermolysis Bullosa Simplex Drug: Botulinic toxin Drug: Placebo Phase 2 Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Each subject is his own witness, receiving the 2 treatments : left foot vs. right foot
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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.
Actual Study Start Date : June 14, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
Experimental: Botulinic toxin
Injections of botulinic toxin (Dysport®, Allergan) 200 UI
Drug: 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

Other Name: Dysport® (experimental drug)

Placebo Comparator: Placebo
Injections of physiological serum
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

Other Name: physiological serum




Primary Outcome Measures :
  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 [ Time Frame: at 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 :
  1. Global clinical improvement on each foot assessed by a blinded centralized independent reviewer using photographs: IGA score (Improvement Global Assessment) for each foot [ Time Frame: at 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

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

  3. Efficacy assessment concerning the number of plantar lesions clinically observed by the investigator [ Time Frame: at baseline, month 1, month 3 and month 6 ]
    on each foot (erythematous and edematous areas, blisters, skin erosion, crusts)

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

  5. Efficacy assessment by the patient himself, for each foot [ Time Frame: at 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)

  6. Plantar pain assessment by the patient himself, for each foot [ Time Frame: at 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).

  7. Immediate tolerance during injection : [ Time Frame: 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

  8. Mid-term and long-term tolerance [ Time Frame: Day 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03453632


Contacts
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Contact: Juliette Mazereeuw-Hautier, MD 5 67 77 81 41 ext 33 mazereeuw-hautier.j@chu-toulouse.fr
Contact: Isabelle DREYFUS, PharmD 5 67 77 81 10 ext 33 dreyfus.i@chu-toulouse.fr

Locations
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France
University Hospital Bordeaux Recruiting
Bordeaux, France, 33000
Contact: Olivier COGREL, MD         
University Hospital Nice Recruiting
Nice, France, 06000
Contact: Christine CHIAVERINI, MD         
Saint-Louis Hospital - APHP Recruiting
Paris, France, 75000
Contact: Emmanuel Bourrat, MD         
Hôpital Larrey - CHU Toulouse Recruiting
Toulouse, France, 31059
Contact: Juliette Mazereeuw-Hautier, Pr         
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
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Principal Investigator: Juliette Mazereeuw-Hautier, MD University Hospital, Toulouse

Publications:
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Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT03453632     History of Changes
Other Study ID Numbers: RC31/16/8917
2017-002332-16 ( EudraCT Number )
First Posted: March 5, 2018    Key Record Dates
Last Update Posted: December 20, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Toulouse:
Dermatology
Rare skin diseases
epidermolysis bullosa simplex
botulinic toxin
blisters
Additional relevant MeSH terms:
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Epidermolysis Bullosa
Epidermolysis Bullosa Simplex
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous
abobotulinumtoxinA
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs