Probiotic Lozenges for Treatment of Recurrent Aphthous Stomatitis (RAS)

Evaluation of the Effect of Probiotic Lozenges in the Treatment of Recurrent Aphthous Stomatitis: a Randomized, Controlled Clinical Trial

The application of host-modulating bacteria for therapeutic purposes is one of the strongest emerging fields. Probiotics are live microorganisms, which, when administered in an adequate amount, confer a health benefit on the host The study aimed to explore the effectiveness of probiotics in the treatment of the common ulcerative condition; minor recurrent aphthous stomatitis (RAS). We included sixty adult (group A) and 60 children patients (group B) with diagnosis of minor RAS . Both groups were divided into two subgroups, AI and BI (test subgroups ) and AII and BII (control subgroups). For test subgroups, probiotic lozenges were consecutively administered twice daily, for five days. The size and pain level of ulcers were recorded on treatment days 0, 3 and 5. The outbreak frequency of RAS within 6 months was investigated for all subgroups.

Study Overview

• Status: Completed
• Conditions: Oral Ulcer
• Intervention / Treatment: Other: Probiotics; Drug: Oracure oral gel

Detailed Description

The study aimed to explore the effectiveness of probiotics in the treatment of minor recurrent aphthous stomatitis (RAS). We performed a randomized, controlled clinical study. Sixty adult (group A) and 60 children patients (group B) with diagnosis of minor RAS were included. Both groups were divided into two subgroups, AI and BI (test subgroups) and AII and BII (control subgroups). For test subgroups, probiotic lozenges were consecutively administered twice daily, for five days. The size and pain level of ulcers were recorded on treatment days 0, 3 and 5. The outbreak frequency of RAS within 6 months was investigated for all subgroups. Compared to baseline, an improvement was evident for all subgroups. However, for effectiveness in pain reduction, a statistically significant difference in favor of AI was observed for all evaluation periods when compared to control subgroup. Regarding effectiveness in ulcer size reduction, a statistically significant difference in favor of BI was observed at day 5 when compared to control subgroup. No significant difference was observed in the effectiveness index between subgroups AI and BI (test subgroups) except in effectiveness in pain reduction at day 3. The outbreak frequency decreased significantly in subgroup BI. We concluded that topical application of probiotics decreased pain intensity and accelerate RAS healing. The effectiveness in pain reduction is more evident in adult patients while acceleration of healing is more evident in children. Probiotics could be a well-tolerated, topical therapeutic agent in the treatment of minor RAS

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 43 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females aged 18-45 years old, 2. Patients presenting with RAS with the following characteristics: a. Minor aphthous ulcers less than 48 hours' duration prior to enrolment, b. Size no greater than 10 mm in diameter, c. A history that ulcers normally more than 5 days to resolve without treatment. The inclusion criteria for group B is the same except age, children with RAS aged between 3 and 12 years were recruited for the study.

Exclusion Criteria:

• A known history of hypersensitivities, immunologic or systemic diseases, pregnancy, smoking,
• treatment with systemic steroid or other immunomodulatory agents within 1 month before the study
• use of nonsteroidal anti-inflammatory drugs or oral antihistamines within 1 month prior to the study
• treatment of the ulcer with any preparation or medication within 72 hours prior to the study
• treatment with systemic antibiotics within 2 weeks prior to the study and a history of adverse reactions to lactose or fermented milk products.
• Children with a positive family history of RAS were excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ChocBalls; (L. acidophilus containing lozenges, PharmaCare Europe Ltd; West Sussex, RH10 9NQ, UK)	Other: Probiotics; Sixty adult (group A) and 60 children patients (group B) with diagnosis of minor RAS were included. Both groups were divided into two subgroups, AI and BI (test subgroups) and AII and BII (control subgroups). For test subgroups, probiotic lozenges were consecutively administered twice daily, for five days. The size and pain level of ulcers were recorded on treatment days 0, 3 and 5. The outbreak frequency of RAS within 6 months was investigated for all subgroups.
Active Comparator: Oracure oral gel (15 gm, Amun pharmaceutical company, Egypt); Each 100 g contains: Lidocaine HCI 2.0g. Cetylpyridinium chloride 0.1 g.	Drug: Oracure oral gel; Sixty adult (group A) and 60 children patients (group B) with diagnosis of minor RAS were included. Both groups were divided into two subgroups, AI and BI (test subgroups) and AII and BII (control subgroups). For control subgroups, oracure gel were consecutively applied twice daily, for five days. The size and pain level of ulcers were recorded on treatment days 0, 3 and 5. The outbreak frequency of RAS within 6 months was investigated for all subgroups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ulcer size reduction	The index ulcer's size was measured on treatment days 0, 3 and 5. The investigators measured the maximum and minimum diameters when the ulcer has an oval shape, using a calibrated dental probe with millimeter markings. The two measurements were then be multiplied to represent the cross-sectional areas of the ulcer.	5 days
Ulcer pain moderation	a visual analog scale (VAS) consisting of a 10-cm horizontal line between poles connoting no pain (origin) to unbearable pain was used. Subjects was told to mark the line with a vertical line at the point that best represented the present pain level of the ulcer	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Outbreak frequency/ 6 months	Participants were asked to estimate the average duration of episodes during the past 6 months and the potential to reduce the outbreak frequency of RAS within the next 6 months was investigated	6 months

Collaborators and Investigators

• Sponsor: Reham Lotfy Aggour
• Investigators: Principal Investigator: Reham Aggour, Dr, Oral Medicine & Periodontology department

Publications and helpful links

General Publications

• Aggour RL, Mahmoud SH, Abdelwhab A. Evaluation of the effect of probiotic lozenges in the treatment of recurrent aphthous stomatitis: a randomized, controlled clinical trial. Clin Oral Investig. 2021 Apr;25(4):2151-2158. doi: 10.1007/s00784-020-03527-7. Epub 2020 Aug 20.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): October 20, 2018
• Study Completion (Actual): April 21, 2019

Study Registration Dates

• First Submitted: May 7, 2020
• First Submitted That Met QC Criteria: May 7, 2020
• First Posted (Actual): May 12, 2020

Study Record Updates

• Last Update Posted (Actual): May 12, 2020
• Last Update Submitted That Met QC Criteria: May 7, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Aphthous, lactobacillus, probiotics
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Mouth Diseases; Oral Ulcer; Stomatitis; Stomatitis, Aphthous
• Other Study ID Numbers: 23-2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No