Epidermolysis Bullosa SimplexPhase 2/3EBToxNCT03453632
Injections of Botulinic Toxin in Plantar Lesions of Localized Epidermolysis Bullosa Simplex
A Phase 2/3 study testing Botulinic toxin in people with Epidermolysis Bullosa Simplex, run by University Hospital, Toulouse at 4 sites in France.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epidermolysis Bullosa Simplex
- What is being tested?
- Botulinic toxin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 4 sitesFrance
- Study dates
- 14 Jun 2018to 21 Jan 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
France4 sites
University Hospital Bordeaux
Bordeaux, 33000
University Hospital Nice
Nice, 06000
Saint-Louis Hospital - APHP
Paris, 75000
Hôpital Larrey - CHU Toulouse
Toulouse, 31059
About this study
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.
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.
- Conditions
- Epidermolysis Bullosa Simplex
- Being tested
- Botulinic toxin, Placebo
- Keywords
- Dermatology, Rare skin diseases, epidermolysis bullosa simplex, botulinic toxin, blisters
- Medical subject headings
- Epidermolysis Bullosa Simplex, Blister
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulinic toxinDrug
Also called Dysport® (experimental 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
PlaceboDrug
Also called physiological serum
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
| Study group | Role | What they receive |
|---|---|---|
| Botulinic toxin | Experimental | Injections of botulinic toxin (Dysport®, Allergan) 200 UI Receives: Drug: Botulinic toxin |
| Placebo | Placebo comparator | Injections of physiological serum Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: at baseline vs month 3
Secondary outcomes (8)
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
Measured: at baseline vs month 6
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
Measured: at month1, month 3 and month 6 respectively vs baseline
Efficacy assessment concerning the number of plantar lesions clinically observed by the investigator
on each foot (erythematous and edematous areas, blisters, skin erosion, crusts)
Measured: at baseline, month 1, month 3 and month 6
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.
Measured: at baseline, month 1, month 3 and month 6
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)
Measured: at month 1, month 3, month 6 and month 9
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).
Measured: at baseline, month 1, month 3 and month 6
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
Measured: Day 0
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.
Measured: Day 0, month 1, month 3 and month 6 and month 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2018
- Study start14 Jun 2018
- Primary completion21 Jan 2025
- Study completion21 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Epidermolysis Bullosa SimplexStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Each subject is his own witness, receiving the 2 treatments : left foot vs. right foot
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Juliette Mazereeuw-Hautier, MD, Principal investigator, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03453632
- Sponsor's protocol ID
- RC31/16/8917
- Other IDs
- 2017-002332-16, 2017
- Acronym
- EBTox
- Status last verified
- Sep 2026
- First submitted
- 6 Feb 2018
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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 24690439Sprecher E. Epidermolysis bullosa simplex. Dermatol Clin. 2010 Jan;28(1):23-32. doi: 10.1016/j.det.2009.10.003.
PubMed 19945613Langan 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 18828848Abitbol 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 19153338Schwieger-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
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03453632
- Acronym / sponsor ID
- EBTox / RC31/16/8917
- Conditions
- Epidermolysis Bullosa Simplex
- Keywords
- Dermatology, Rare skin diseases, epidermolysis bullosa simplex, botulinic toxin, blisters
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- 14 Jun 2018 (actual)
- Primary completion
- 21 Jan 2025 (actual)
- Study completion
- 21 Jan 2025 (actual)
- First posted
- 5 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Each subject is his own witness, receiving the 2 treatments : left foot vs. right foot
| Arm | Type | Receives |
|---|---|---|
| Botulinic toxin | Experimental | Drug: Botulinic toxinInjections of botulinic toxin (Dysport®, Allergan) 200 UI |
| Placebo | Placebo comparator | Drug: PlaceboInjections of physiological serum |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Botulinic toxinAlso: Dysport® (experimental 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 | Drug | Botulinic toxin |
| PlaceboAlso: physiological serumClinical 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 | Drug | Placebo |
Primary outcome
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
8 secondary outcomes
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
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
Efficacy assessment concerning the number of plantar lesions clinically observed by the investigator
Time frame: at baseline, month 1, month 3 and month 6
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
Efficacy assessment by the patient himself, for each foot
Time frame: at month 1, month 3, month 6 and month 9
Plantar pain assessment by the patient himself, for each foot
Time frame: at baseline, month 1, month 3 and month 6
Immediate tolerance during injection :
Time frame: Day 0
Mid-term and long-term tolerance
Time frame: Day 0, month 1, month 3 and month 6 and month 9
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Background: PubMed 24690439Fine 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.
- Background: PubMed 19945613Sprecher E. Epidermolysis bullosa simplex. Dermatol Clin. 2010 Jan;28(1):23-32. doi: 10.1016/j.det.2009.10.003.
- Background: PubMed 18828848Langan 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.
- Background: PubMed 19153338Abitbol 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.
- Background: PubMed 24650374Schwieger-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juliette Mazereeuw-Hautier, MD principal investigator
University Hospital, Toulouse
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Botulinic toxin in people with Epidermolysis Bullosa Simplex, run by University Hospital, Toulouse at 4 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03453632, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.