Botulinumtoxin A Treatment in Epidermolysis Bullosa Simplex and Pachyonychia Congenita

Study Overview
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Brief Summary
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This study evaluates the clinical effect of foot injection of the bacteria protein Botulinum toxin A on plantar pain in patients with EBS (epidermolysis bullosa simplex) or PC (pachyonychia congenita).

Detailed Description
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Epidermolysis bullosa simplex (EBS) is the most common subtype of epidermolysis bullosa and mutations in keratin genes (KRT 5/14) are responsible for this condition. Painful blisters and keratoderma of the feet are common and the blisters in EBS typically get worse in the summer due to sweating and increased environmental heat. Since 2010, also the related condition pachyonychia congenita (PC) is included in the study. The primary objective of the study is to evaluate the clinical effect of Botulinum toxin A (Dysport®), injected in the foot, on plantar pain in patients with EBS or PC. Quality of life, pain in feet, effect duration, plantar sweating and safety of the treatment will also be studied.

Official Title
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Botulinumtoxin A Treatment in Epidermolysis Bullosa Simplex and Pachyonychia Congenita - a Double-blind Placebo-controlled Phase II Proof of Concept Study

Conditions
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Epidermolysis Bullosa Simplex

Intervention / Treatment
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* Drug: Dysport® (Botulinumtoxin A (Btx A))
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent received from patient Informed consent received from patient´s parents (when patient < 18 years) A solid EBS-diagnosis based on genetic analysis and/or phenotype. The EBS-diagnosis will be performed by Professor Anders Vahlquist, Swedish Centre of Genetic skin disorders, Uppsala. Age > 16 years Patients must be previously untreated with Btx A If female, patient is post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control Exclusion Criteria: Contraindication to Btx A Contraindication to general anaesthesia Use of aminoglycosides, tetracyclines , spectinomycin, lincomycin, polymyxin or muscle relaxants Pregnancy or lactation Patients unwilling to meet the requirements of the protocol Other medical or social reasons for exclusion at the discretion of the Investigator

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Dysport® (Botulinumtoxin A (Btx A))|Single injection in patients´ soles with Btx A in one foot and sodium chloride in the other, with the possibility of a second injection after 12 weeks. The drug will be given in general anaesthesia after curettage of the focal hyperkeratoses. Only the areas with focal hyperkeratoses will be injected with 50 ul per injection.The active drug Btx A (Dysport®, solution for injection) has a concentration of 100 U/ml, and the maximum dose is 300 U per foot.|
|Drug: Placebo|Placebo preparation without active compound, administered as the active drug.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the difference between treated and untreated foot in change of pressure (measured by manometry) to reach unbearable pain, VAS=8, from baseline to 5 week after injection. |  | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life using a questionnaire (DLQI) |  | 12 or 17 weeks | 
| Pain in feet using a questionnaire (VAS) |  | 5, 12 (and 17) weeks | 
| Effect duration measured with manometry (same as primary end-point but measured at week 12) |  | 12 weeks | 
| Safety by recording of reported adverse events (AE) by the patient at the clinic visits |  | 5, 12 (and 17) weeks | 
| Foot-sweating using iodine-starch imprints before and after injections |  | 0 weeks |