The Effect of Oral Probiotics on Oral Hygiene and Halitosis in Orthodontic Patients.

Study Overview
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Brief Summary
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Brackets, bands, ligatures and wires in patients receiving orthodontic treatment with fixed appliances are areas that trap food and impede oral hygiene. An ecological environment facilitating the growth of microorganisms (Actinobacillus, Bacteroides, Prevotella etc.) emerges in the mouth and may cause caries, enamel white spots, gingival inflammation and halitosis. Despite the use of specialized orthodontic brushes, interdental brushes, mouthwashes and topical fluorides, plaque removal remains inadequate in patients with fixed orthodontic appliances. On the other hand, patients undergoing orthodontic treatment with aligners have been found to have better oral hygiene because of less plaque accumulation in their mouth. Probiotics are defined as non-pathogenic bacteria that can benefit the host's general health when taken in sufficient amounts through nutrition. Nowadays probiotics can be used to enhance oral health as they are found to reduce dental bioﬁlm formation, prevent and decrease halitosis in children, adolescents and adults. To date, there are few randomized controlled trials (RCTs) examining the efﬁcacy of oral probiotics in patients with fixed orthodontic appliances and none reporting the incidence of halitosis and the effect of probiotics in orthodontic patients wearing aligners.

Detailed Description
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The aim of the study is to investigate the effect of the oral probiotic Lactobacillus salivarius on oral hygiene indices and halitosis in patients wearing orthodontic braces and patients wearing orthodontic aligners. The study is a prospective, randomized, placebo-controlled, double blinded, with four parallel groups and an equal allocation ratio in all groups. Patients 12-18 years old undergoing ﬁxed orthodontic treatment will be randomly allocated to probiotic group A (n=30) and placebo group B (n=30). Patients ≥18 years old wearing aligners (Invisalign™ ) will be randomly allocated to probiotic group C (n=30) and placebo group D (n=30). All participants will consume lozenges for one month. Assessments will be taken at baseline, at the end of the intervention and at a 2 month free-intervention follow-up. The outcome measures will be modified plaque index (PI), modified gingival index (GI) and halitosis-causing volatile sulfur compound (VSC) levels. Results will be announced at the end of the study.

Official Title
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The Effect of Oral Probiotics on Oral Hygiene and Halitosis in Orthodontic Patients: a Randomized Controlled Trial

Conditions
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Halitosis, Probiotics, Orthodontic Appliance Complication

Intervention / Treatment
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* Dietary Supplement: Prodilac Oral, Frezyderm
* Dietary Supplement: placebo lozenges


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients eligible for the trial must comply with all of the following at randomization: Age between 12 and 18 years for the group with conventional orthodontic appliances This age group represents the majority of patients seeking orthodontic treatment and is homogeneous regarding occupational status (high-school and lyceum students in Greece). Younger patients might present with cooperation problems. Age ≥18 for the Invisalign™ group This age group represents the majority of patients seeking orthodontic with aligners (Invisalign™) regarding social status and other factors. Good general health Fixed orthodontic appliances Patients should have fixed labial appliances (brackets) on all teeth from central incisor to first molar, in both the maxillary and the mandibular arch. Fixed appliances should have been placed at least two months before the patient is accepted into the study and remaining treatment should be at least 3 months. All brackets will be the same (metallic, conventional/not self-ligating, same size). Molars should be banded (same bands on all molars) and all other teeth bonded. At least 20 natural teeth (in case of extraction orthodontic treatment patients can be enrolled two months after extractions) The outcomes will be evaluated at all teeth from first molar to first molar. Exclusion Criteria: Patients will be excluded for any of the following reasons: Active caries Periodontitis Syndromes, mental disabilities and craniofacial deformities Smoking or use of other tobacco products Dental fluorosis/tooth malformation Antibiotics during the last 2 months chlorhexidine in the previous 3 week Suffering from any disease within 2 months before measurements Allergy to dairy products Participation in other trials Consent / assent Parents/guardians and patients will provide written informed consent and patients will provide written assent before randomization and before any procedures are applied.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This trial is designed as a prospective, randomized, placebo-controlled, double (investigator and patient) blinded, with four parallel groups and an equal allocation ratio in all groups. In this dose study, the intervention consists of delivery of oral probiotics Lactobacillus Salivarius or placebo lozenges. Equal number of males and females will be allocated to each group. In our study oral probiotics Lactobacillus salivarius Oral S1 11 (Prodilac Oral, Frezyderm) will be tested in two different groups: Experimental group 1: patients, age 12-18, conventional brackets, Oral probiotics lozenges Experimental group 2: patients, age ≥18, Invisalign™ appliances, Oral probiotics lozenges Control group 1: patients, age 12-18, conventional brackets, placebo lozenges Control group 2: patients, age ≥18, Invisalign™ appliances, placebo lozenges
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group 1: patients, age 12-18, conventional brackets, Oral probiotics lozenges<br>30 patients, age 12-18,with conventional brackets,will get Oral probiotics lozenges | Dietary Supplement: Prodilac Oral, Frezyderm<br>* In our study oral probiotics Lactobacillus salivarius Oral S1 11 (Prodilac Oral, Frezyderm) will be tested in two Experimental groups<br>|
| Experimental: Experimental group 2: patients, age ≥18, Invisalign™ appliances, Oral probiotics lozenges<br>30 patients, age ≥18, Invisalign™ appliances,wil get Oral probiotics lozenges | Dietary Supplement: Prodilac Oral, Frezyderm<br>* In our study oral probiotics Lactobacillus salivarius Oral S1 11 (Prodilac Oral, Frezyderm) will be tested in two Experimental groups<br>|
| Placebo Comparator: Control group 1: patients, age 12-18, conventional brackets, placebo lozenges<br>30 patients, age 12-18, conventional brackets,will get placebo lozenges | Dietary Supplement: placebo lozenges<br>* In order to avoid possible bias, probiotics will be compared with placebo lozenges/no probiotic in two Control groups<br>|
| Placebo Comparator: Control group 2: patients, age ≥18, Invisalign™ appliances, placebo lozenges<br>30 patients, age ≥18, Invisalign™ appliances,will get placebo lozenges | Dietary Supplement: placebo lozenges<br>* In order to avoid possible bias, probiotics will be compared with placebo lozenges/no probiotic in two Control groups<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Silness and Löe plaque index (PI-M) | The Silness and Löe index does not take into account the pattern of plaque accumulation in orthodontic patients. To overcome this problem, divided the tooth into mesial, distal, gingival, and incisal regions in relation to the bracket and scored plaque in each region using the four codes of the original index (0 to 3). The values are summed to obtain a total score, which ranges from 0 to 12 for each tooth. This modified index is recommended for patients with fixed orthodontic appliances because it acknowledges the usual effects of orthodontic appliances on plaque distribution and has much greater categorical discrimination. | baseline-1 month | 
| Modified Silness and Löe plaque index (PI-M) | The Silness and Löe index does not take into account the pattern of plaque accumulation in orthodontic patients. To overcome this problem, divided the tooth into mesial, distal, gingival, and incisal regions in relation to the bracket and scored plaque in each region using the four codes of the original index (0 to 3). The values are summed to obtain a total score, which ranges from 0 to 12 for each tooth. This modified index is recommended for patients with fixed orthodontic appliances because it acknowledges the usual effects of orthodontic appliances on plaque distribution and has much greater categorical discrimination. | 1 month- 3 month | 
| Modified Gingival index (GI-M) | The Gingival Index (GI) is a measure of the severity of gingivitis and is scored by measuring the amount of gingival inflammation, also considering redness and bleeding . | baseline-1 month | 
| Modified Gingival index (GI-M) | The Gingival Index (GI) is a measure of the severity of gingivitis and is scored by measuring the amount of gingival inflammation, also considering redness and bleeding. | 1 month- 3 month | 
| Halitosis/ VSCs levels | VSCs levels will recorded at each time point with the use of OralChromaTM. OralChromaTM is a portable gas chromatograph, which uses ambient air as a carrier gas and a semiconductor (In2O3) gas sensor to detect volatile sulphur compounds (VSCs), i.e. the concentrations of H2S, CH3SH and (CH3)2S. | baseline-1 month | 
| Halitosis/ VSCs levels | VSCs levels will recorded at each time point with the use of OralChromaTM. OralChromaTM is a portable gas chromatograph, which uses ambient air as a carrier gas and a semiconductor (In2O3) gas sensor to detect volatile sulphur compounds (VSCs), i.e. the concentrations of H2S, CH3SH and (CH3)2S. | 1 month- 3 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Halitosis, Probiotics, Fixed Appliances, Aligners