Influence of Probiotics on Clinical Parameters, the Oral Microbiome and the Immune System During an Orthodontic Treatment

Influence of Probiotics on Clinical Parameters, the Oral Microbiome and the Immune System During an Orthodontic Treatment: a Prospective, Double-blind, Randomized, Clinical Study

Orthodontic treatment with fixed appliances can be necessary to correct malocclusions in adolescence or adulthood. It its known that orthodontic treatment induces aseptic pseudo-inflammatory reactions. However, studies could show that an increase of certain inflammatory cytokines during orthodontic treatment correlated with a higher risk of root resorption. Moreover, it has been shown that orthodontic treatment leads to a dysbiosis of the oral microbiome especially during the first 3 months of the orthodontic treatment. This could be a potential risk factor as the inflammation of periodontitis during an orthodontic treatment could favor root resorption and progressive destruction of the periodontal apparatus.

Probiotics are already used successfully as an adjuvant therapy in the treatment of periodontitis to improve clinical parameters and to reduce local inflammation. However, there are only a few studies that investigated the influence of probiotics during an orthodontic treatment.

Therefore, the aim of the study is to investigate if the daily intake of lozenges containing probiotics versus placebo lozenges during the first 3 months of orthodontic treatment with fixed appliances can improve clinical parameters, reduce local inflammation and prevent a dysbiosis of the oral microbiome.

Study Overview

• Status: Recruiting
• Conditions: Gingivitis; Orthodontic Appliance Complication
• Intervention / Treatment: Dietary supplement: Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289); Dietary supplement: Placebo-lozenges (BioGaia)

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Corinna Lesley Seidel, Dr.; Phone Number: ++49-09131-85-45667; Email: corinna.boeck@uk-erlangen.de
• Study Contact Backup: Name: Lina Gölz, Prof.Dr.; Phone Number: ++ 49 (0)9131 85-33643; Email: lina.goelz@uk-erlangen.de

Study Locations

• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Recruiting
      • UniversityHospitalErlangen-Nurenberg
      • Principal Investigator: Corinna L Seidel, Dr.
      • Contact: Corinna L Seidel, Dr.; Phone Number: 091318545667 091318545667; Email: corinna.seidel@uk-erlangen.de
      • Contact: Lina L Gölz, Prof.; Phone Number: 091318545667 091318533643; Email: lina.goelz@uk-erlangen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adolescents from age 12 to 17 with fixed appliances undergoing orthodontic treatment
• Signed declaration of consent by the patient and the parent or legal guardian for adolescent patients

Exclusion Criteria:

• Systemic or metabolic disease that are related to gingivitis or (e.g. diabetes) or could possibly influence the oral microbiome

• obesity:

  -adolescents: body mass index > + 2 standard deviations (SD) over the average value given by the World Health Organisation (weight and height will be measured)

• Eating disorder or underweight

  -adolescents: BMI > -2 SD under the average value given by the WHO (weight and height will be measured)

• Above-average consumption of milk products: > 3 portions/day = >1,2 liters of milk or 1200g yoghurt/day (daily dose recommended by the german society for nutrition = 1-3 portions of milk products)
• allergy to ingredients of the lozenges
• intake of antibiotics or dietary supplementation (probiotics, vitamin C/D) in the last 6 months or during the study
• regular use of antibacterial mouth wash
• pregnancy
• smoking
• retraction of the declaration of consent by the patient and the parent or legal guardian for adolescent patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lactobacillus reuteri Prodentis®-lozenges	Dietary supplement: Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289); Supplementary intake of Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289) 2 times per day for 12 weeks
Placebo Comparator: Placebo-lozenges (BioGaia)	Dietary supplement: Placebo-lozenges (BioGaia); Placebo-lozenges (BioGaia) 2 times per day for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gingival Index (GI)	Primary endpoint is the change of the Gingival Index (GI) from baseline to week 4. The measurement of GI is described by Löe et al, which scores the gingival condition according to the defined criteria. The scores will be measured at four sites per tooth, added and divided by four to obtain the "GI for the tooth"-Index. We will use the 'GI for the tooth' described there, but only for those teeth with fixed ortodontic brackets. The 'GI for the patient' is then the mean of the GIs for the teeth. CRITERIA FOR THE GINGIVAL INDEX SYSTEM 0 = Absence of inflammation.; = Mild inflammation - slight cliange in color and little change in texture.; = Moderate inflammation - modcrate glazing, redness,oedema, hypertrophy, bleeding on pressure.; = Severe inflammation - marked redness and hypertrophy, tendency to spontaneous bleeding, ulceration.	Baseline to week 4 of intake

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local cytokine expression	Samples from different oral niches (saliva, soft and hard tissue samples, gingival crevicular fluid) will be collected to analyse local inflammation: Unstimulated saliva will be gained by the spitting method, soft tissue samples will be collected in using sterile swabs, hard tissue samples of supragingival plaque will taken by sterile curettes and samples of gingival sulcus fluid will be collected from 6 periodontal pockets of the mesio-buccal side of defined teeth (Ramfjord teeth: 16,21,24,36,41,44) using sterile paper strips. Sulcus fluid flow rate will be performed using Periotron 8000. The cytokine concentration (in pg/mL) of granulocyte-macrophage colony-stimulating-factor (GM-CSF), interferon (IFN)- gamma, interleukin (IL)-2, IL-4, IL-6, IL-8 and IL-10 as well as tumor necrosis factor (TNF) in defined oral niches will be measured using multiplex immunoassay.	Baseline till 12 months after insertion of appliance
Oral microbiome	Samples from different oral niches (saliva, soft and hard tissue samples, gingival crevicular fluid) will be collected to analyse the oral microbiome: Unstimulated saliva will be gained by the spitting method, soft tissue samples will be collected in using sterile swabs, hard tissue samples of supragingival plaque will taken by sterile curettes and samples of gingival sulcus fluid will be collected from 6 periodontal pockets of the mesio-buccal side of defined teeth (Ramfjord teeth: 16,21,24,36,41,44) using sterile paper strips. Composition of the oral microbiome will be analysed using 16 S rRNA sequencing and operational taxonomic units (OTUs) will be classified according to SILVA database.	Baseline till 12 months after insertion of appliance
Probing pocket depth (PPD) (4-point-measurement)	The measuremtn of the probing of periodontal pockets (periodontal probing depth, PPD) is performed according to standardized protocols: insertion of a perdiotonal probe into the gingival sulcus with a force of 0.2-0.3 N; probing depth is read out at landmarks on the periodontal prove. The scores will be measured at four sites per tooth, added and divided by four to obtain the "PPDI for the tooth"-Index. We will use the 'PPD for the tooth', but only for those teeth with fixed ortodontic brackets. The 'PPD for the patient' is then the mean of the PPDs for the teeth.	Baseline till 12 months after insertion of appliance
Modified Plaque Index (MPI)	The measurement of Modified plaque index (MPI) is described by Attin et al, which scores the amount of plaque according to the defined criteria. The score will be measured at each tooth, but only for those teeth with fixed ortodontic brackets. The 'Modified plaque index for the patient' is then the mean of the MPIs per teeth: Index = (Sum of MPI per tooth×100)/ (3×number of measured teeth). CRITERIA FOR THE MODIFIED PLAQUE INDEX 0 = no plaque; = small plaque areas approximal; = small plaque areas approximal + cervical; = plaque covers 1/3 of the cervical area of the bracket	Baseline till 12 months after insertion of appliance

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Collection of adverse Events.	Baseline till 12 months after insertion of appliance.

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg
• Collaborators: BioGaia AB
• Investigators: Study Director: Corinna Lesley Seidel, Dr., Department of Orthodontics and Orofacial Orthopedics; Study Director: Lina Gölz, Prof.Dr., Department of Orthodontics and Orofacial Orthopedics

Publications and helpful links

General Publications

• Seidel CL, Gerlach RG, Weider M, Wolfel T, Schwarz V, Strobel A, Schmetzer H, Bogdan C, Golz L. Influence of probiotics on the periodontium, the oral microbiota and the immune response during orthodontic treatment in adolescent and adult patients (ProMB Trial): study protocol for a prospective, double-blind, controlled, randomized clinical trial. BMC Oral Health. 2022 Apr 27;22(1):148. doi: 10.1186/s12903-022-02180-8.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: September 9, 2020
• First Submitted That Met QC Criteria: October 18, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Orthodontics; Inflammation; Microbiome; Probiotics
• Additional Relevant MeSH Terms: Infections; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Gingival Diseases; Gingivitis
• Other Study ID Numbers: ER-Ortho-Pro-RCT-1

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