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

Epidermolysis Bullosa Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05288478
• Other study ID #: PRI-ODO 2021/16
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: April 6, 2022
• Est. completion date: March 2023

Study information

• Verified date: April 2022
• Source: University of Chile
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 100
• Est. completion date: March 2023
• Est. primary completion date: August 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Epidermolysis Bullosa
• Oral Ulcer

Intervention

Combination Product:
• Dentoxol mouthrinse dosages
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.

Locations

Country	Name	City	State
Chile	Facultad de Odontología, Universidad de Chile	Santiago	Región Metropolitana

Sponsors (2)

Lead Sponsor	Collaborator
University of Chile	Fundación Debra Chile

Country where clinical trial is conducted

Chile, 

References & Publications (19)

Brun J, Chiaverini C, Devos C, Leclerc-Mercier S, Mazereeuw J, Bourrat E, Maruani A, Mallet S, Abasq C, Phan A, Vabres P, Martin L, Bodemer C, Lagrange S, Lacour JP; Research Group of the French Society of Pediatric Dermatology. Pain and quality of life evaluation in patients with localized epidermolysis bullosa simplex. Orphanet J Rare Dis. 2017 Jun 28;12(1):119. doi: 10.1186/s13023-017-0666-5. — View Citation

Cheng KK. Children's acceptance and tolerance of chlorhexidine and benzydamine oral rinses in the treatment of chemotherapy-induced oropharyngeal mucositis. Eur J Oncol Nurs. 2004 Dec;8(4):341-9. — View Citation

Fortuna G, Aria M, Cepeda-Valdes R, Pollio A, Moreno-Trevino MG, Salas-Alanís JC. Clinical features of gingival lesions in patients with dystrophic epidermolysis bullosa: a cross-sectional study. Aust Dent J. 2015 Mar;60(1):18-23. doi: 10.1111/adj.12264. — View Citation

Fortuna G, Lozada-Nur F, Pollio A, Aria M, Cepeda-Valdes R, Marinkovich MP, Bruckner AL, Salas-Alanís JC. Patterns of oral mucosa lesions in patients with epidermolysis bullosa: comparison and agreement between oral medicine and dermatology. J Oral Pathol Med. 2013 Nov;42(10):733-40. doi: 10.1111/jop.12094. Epub 2013 Jun 15. — View Citation

Has C, Bauer JW, Bodemer C, Bolling MC, Bruckner-Tuderman L, Diem A, Fine JD, Heagerty A, Hovnanian A, Marinkovich MP, Martinez AE, McGrath JA, Moss C, Murrell DF, Palisson F, Schwieger-Briel A, Sprecher E, Tamai K, Uitto J, Woodley DT, Zambruno G, Mellerio JE. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020 Oct;183(4):614-627. doi: 10.1111/bjd.18921. Epub 2020 Mar 11. Review. — View Citation

Has C, Liu L, Bolling MC, Charlesworth AV, El Hachem M, Escámez MJ, Fuentes I, Büchel S, Hiremagalore R, Pohla-Gubo G, van den Akker PC, Wertheim-Tysarowska K, Zambruno G. Clinical practice guidelines for laboratory diagnosis of epidermolysis bullosa. Br J Dermatol. 2020 Mar;182(3):574-592. doi: 10.1111/bjd.18128. Epub 2019 Aug 9. — View Citation

Korolenkova MV. [Dental treatment in children with dystrophic form of epidermolysis bullosa]. Stomatologiia (Mosk). 2015;94(2):34-36. doi: 10.17116/stomat201594234-36. Russian. — View Citation

Krämer S, Lucas J, Gamboa F, Peñarrocha Diago M, Peñarrocha Oltra D, Guzmán-Letelier M, Paul S, Molina G, Sepúlveda L, Araya I, Soto R, Arriagada C, Lucky AW, Mellerio JE, Cornwall R, Alsayer F, Schilke R, Antal MA, Castrillón F, Paredes C, Serrano MC, Clark V. Clinical practice guidelines: Oral health care for children and adults living with epidermolysis bullosa. Spec Care Dentist. 2020 Nov;40 Suppl 1:3-81. doi: 10.1111/scd.12511. — View Citation

Kummer TR, Nagano HC, Tavares SS, Santos BZ, Miranda C. Oral manifestations and challenges in dental treatment of epidermolysis bullosa dystrophica. J Dent Child (Chic). 2013 May-Aug;80(2):97-100. — View Citation

Lalla RV, Solé S, Becerra S, Carvajal C, Bettoli P, Letelier H, Santini A, Vargas L, Cifuentes A, Larsen F, Jara N, Oyarzún J, Feinn R, Bustamante E, Martínez B, Rosenberg D, Galván T. Efficacy and safety of Dentoxol® in the prevention of radiation-induced oral mucositis in head and neck cancer patients (ESDOM): a randomized, multicenter, double-blind, placebo-controlled, phase II trial. Support Care Cancer. 2020 Dec;28(12):5871-5879. doi: 10.1007/s00520-020-05358-4. Epub 2020 Apr 8. — View Citation

Marini I, Vecchiet F. Sucralfate: a help during oral management in patients with epidermolysis bullosa. J Periodontol. 2001 May;72(5):691-5. — View Citation

Mello BZ, Neto NL, Kobayashi TY, Mello MB, Ambrosio EC, Yaedú RY, Machado MA, Oliveira TM. General anesthesia for dental care management of a patient with epidermolysis bullosa: 24-month follow-up. Spec Care Dentist. 2016 Jul;36(4):237-40. doi: 10.1111/scd.12170. Epub 2016 Mar 2. — View Citation

Oliveira TM, Sakai VT, Candido LA, Silva SM, Machado MA. Clinical management for epidermolysis bullosa dystrophica. J Appl Oral Sci. 2008 Jan-Feb;16(1):81-5. — View Citation

Pekiner FN, Yücelten D, Ozbayrak S, Sezen EC. Oral-clinical findings and management of epidermolysis bullosa. J Clin Pediatr Dent. 2005 Fall;30(1):59-65. Review. — View Citation

Puliyel D, Chiu CH, Habibian M. Restorative and periodontal challenges in adults with dystrophic epidermolysis bullosa. J Calif Dent Assoc. 2014 May;42(5):313-8. — View Citation

Sindici E, Astesano S, Fazio L, Dragonetti A, Pugliese M, Scully C, Carossa S, Broccoletti R, Arduino PG. Treatment of Oral Lesions in Dystrophic Epidermolysis Bullosa: A Case Series of Cord Blood Platelet Gel and Low-level Laser Therapy. Acta Derm Venereol. 2017 Mar 10;97(3):383-384. doi: 10.2340/00015555-2512. — View Citation

Stellingsma C, Dijkstra PU, Dijkstra J, Duipmans JC, Jonkman MF, Dekker R. Restrictions in oral functions caused by oral manifestations of epidermolysis bullosa. Eur J Dermatol. 2011 May-Jun;21(3):405-9. doi: 10.1684/ejd.2011.1356. — View Citation

Uitto J. Toward treatment and cure of epidermolysis bullosa. Proc Natl Acad Sci U S A. 2019 Dec 11. pii: 201919347. doi: 10.1073/pnas.1919347117. [Epub ahead of print] — View Citation

Wright JT. Comprehensive dental care and general anesthetic management of hereditary epidermolysis bullosa. A review of fourteen cases. Oral Surg Oral Med Oral Pathol. 1990 Nov;70(5):573-8. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Patients compliance with treatment.	Daily record of mouthrinse use.	16 weeks
Secondary	Patients acceptance of mouthrinse use	Mouthrinse Acceptance Form (Validated Questionnaire)	16 weeks