Dose-ranging Study of Dentoxol® Mouthrinse for Managing Oral Symptoms in People With Epidermolysis Bullosa.

Study Overview
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Brief Summary
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Inherited Epidermolysis Bullosa (EB) is a disorder that causes skin fragility and blistering in skin and mucous membranes, including the mouth. Recurrent oral blisters and ulcer result in oral pain and discomfort. Dentoxol® is a mouthrinse that has anti-inflammatory, antimicrobial and analgesic effects. It has significant potential to reduce EB related oral symptoms. This study includes people living with Inherited Epidermolysis Bullosa aged 6 and above; and is aimed at determining the efficacy of two different dose regimens of Dentoxol mouthrinse in reducing oral symptoms.

Detailed Description
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Inherited Epidermolysis Bullosa (EB) is a group of genetic disorders with skin fragility and blistering. In addition to the skin, it can affect the mucous membranes, causing oral symptoms including oral pain and discomfort due to recurrent oral blisters, ulcers and erosions. Dentoxol® is a proprietary mouthrinse that has anti-inflammatory, antimicrobial and analgesic effects. This three-pronged strategy therefore has significant potential to reduce EB related oral symptoms. Preliminary reports of Dentoxol® mouthrinse have suggested that it is safe and effective in reducing the EB related oral symptoms.Therefore, a well-controlled Phase II study is now warranted. This study will include people living with Inherited Epidermolysis Bullosa aged 6 and over, and seeks to determinate the efficacy of two different dose regimens of Dentoxol mouthrinse in reducing the symptoms mentioned above. Methods: 100 subjects with EB will be recruited and will be given Dentoxol® mouthrinse for two periods of 6 weeks using different dose regimes. Subjects will have a dose regimen assigned randomly, group A: first 6 weeks will be asked to rinse 5 times a day, followed by a 4 weeks washout period and the second 6 weeks period: twice a day. Group B: first 6 weeks 2 times a day, second 6 weeks period: 5 times a day, both with a 4 week washout period in between. On week 0, 1, 3 and 6 of each regime patients living in the metropolitan area will be examined by the Oral Medicine specialist.

Official Title
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Phase II Dose-ranging Study of Dentoxol® Mouthrinse for Managing Oral Symptoms in Epidermolysis Bullosa.

Conditions
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Epidermolysis Bullosa, Oral Ulcer

Intervention / Treatment
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* Combination Product: Dentoxol mouthrinse dosages


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: People living with Inherited Epidermolysis Bullosa, including all types and subtypes, registered at Debra Foundation at the country of the study. Exclusion Criteria: Unable to give written informed consent / assent. Have used a mouth rinse aimed at managing oral ulcers in the last 4 weeks. Known allergy/intolerance to any component of the study rinse. Planning to use any of the following contraindicated medications during the study period (pain medications are allowed) Any agent marketed for oral mucositis Steroids Antibiotics (eg, tetracyclines) (Note: topical antifungals are allowed) Povidone iodine Sucralfate and other coating agents such as Gelclair, MuGard, etc. Caphosol Chlorhexidine Gluconate (Oralgene, Perioaid, Peridex, Periogard) Diphenhydramine (Benadryl) Laser therapy for oral mucositis Any other anti-inflammatory agent Any other investigative agent *Note: Miracle / Magic rinse preparations containing viscous lidocaine are allowed, however, diphenhydramine and other excluded agents should not be added. Age below 6 years Pregnant or nursing Unable to rinse the mouth due to limited oral functioning.

Ages Eligible for Study
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Minimum Age: 6 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: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 100 subjects with EB will be recruited, divided into groups according to their mayor type of EB and subtype, they will use Dentoxol® mouthrinse twice a day or 5 times each day. Subjects will have a dose regimen assigned randomly, group A: first 6 weeks 5 times a day, following 6 weeks twice a day, and group B: first 6 weeks 2 times a day following 6 weeks 5 times a day, both with a 4 week washout period in between. On week 0, 1, 3 and 6 of each regime patients living in the metropolitan area will be examined by the Oral Medicine specialist.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>First 6 weeks they will use the mouthrinse 5 times a day, following 4 week washout period. | Combination Product: Dentoxol mouthrinse dosages<br>* Subjects will have a dose regimen assigned randomly, group A: first 6 weeks 5 times a day, following 6 weeks twice a day, and group B: first 6 weeks 2 times a day following 6 weeks 5 times a day, both with a 4 week washout period in between.<br>|
| Active Comparator: Group A, second period<br>After the washout period, the next 6 weeks the will use the mouthrinse twice a day. On week 0, 1, 3 and 6 of each regime patients living in the metropolitan area will be examined by the Oral Medicine specialist. | Combination Product: Dentoxol mouthrinse dosages<br>* Subjects will have a dose regimen assigned randomly, group A: first 6 weeks 5 times a day, following 6 weeks twice a day, and group B: first 6 weeks 2 times a day following 6 weeks 5 times a day, both with a 4 week washout period in between.<br>|
| Active Comparator: Group B<br>First 6 weeks they will use the mouthrinse twice a day, following 4 week washout period | Combination Product: Dentoxol mouthrinse dosages<br>* Subjects will have a dose regimen assigned randomly, group A: first 6 weeks 5 times a day, following 6 weeks twice a day, and group B: first 6 weeks 2 times a day following 6 weeks 5 times a day, both with a 4 week washout period in between.<br>|
| Active Comparator: Group B, second period<br>After the washout period, the next 6 weeks they will use the mouthrinse 5 times a day. On week 0, 1, 3 and 6 of each regime patients living in the metropolitan area will be examined by the Oral Medicine specialist. | Combination Product: Dentoxol mouthrinse dosages<br>* Subjects will have a dose regimen assigned randomly, group A: first 6 weeks 5 times a day, following 6 weeks twice a day, and group B: first 6 weeks 2 times a day following 6 weeks 5 times a day, both with a 4 week washout period in between.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in oral symptoms associated to oral bullae, erosions and ulcerations in adults and children over the age of 6 living with Epidermolysis Bullosa with two different dose regimes of Dentoxol® mouthrinse and compare both effects. | Epidermolysis Bullosa Oral Health Questionnaire (EBOHQ) | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the duration of the lesions with two different dose regimes of Dentoxol® mouthrinse and compare both effects. | Epidermolysis Bullosa Oral Health Questionnaire (EBOHQ) (Validated Questionnaire) | 16 weeks | 
| Change in the frequency of the lesions with two different dose regimes of Dentoxol® mouthrinse and compare both effects. | Epidermolysis Bullosa Oral Health Questionnaire (EBOHQ) (Validated Questionnaire) | 16 weeks | 
| Change in the recurrence of the lesions with two different dose regimes of Dentoxol® mouthrinse and compare both effects. | Epidermolysis Bullosa Oral Health Questionnaire (EBOHQ) (Validated Questionnaire) | 16 weeks | 
| Change in the size of the lesions with two different dose regimes of Dentoxol® mouthrinse and compare both effects. | Epidermolysis Bullosa Oral Health Questionnaire (EBOHQ) (Validated Questionnaire) | 16 weeks | 
| Change in the number of the lesions with two different dose regimes of Dentoxol® mouthrinse and compare both effects. | Epidermolysis Bullosa Oral Health Questionnaire (EBOHQ) (Validated Questionnaire) | 16 weeks | 
| Change in the distribution of the lesions with two different dose regimes of Dentoxol® mouthrinse and compare both effects. | Epidermolysis Bullosa Oral Health Questionnaire (EBOHQ) (Validated Questionnaire) | 16 weeks | 
| Change in oral pain with two different dose regimes of Dentoxol® mouthrinse and compare both effects. | Epidermolysis Bullosa Oral Health Questionnaire (EBOHQ) (Validated Questionnaire) | 16 weeks | 
| Improve the oral health related quality of life and oral functioning with two different dose regimes of Dentoxol® mouthrinse and compare both effects. | Epidermolysis Bullosa Oral Health Questionnaire (EBOHQ) (Validated Questionnaire) | 16 weeks | 
| Patients compliance with treatment. | Daily record of mouthrinse use. | 16 weeks | 
| Patients acceptance of mouthrinse use | Mouthrinse Acceptance Form (Validated Questionnaire) | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epidermolysis Bullosa, Oral ulcer, Oral blisters, Dentoxol mouthrinse