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

Primary Purpose

Gingivitis, Periodontal Inflammation, Orthodontic Appliance Complication

Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289)
Placebo-lozenges (BioGaia)
Sponsored by
University of Erlangen-Nürnberg
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Gingivitis focused on measuring Orthodontics, Inflammation, Microbiome, Probiotics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Adults (18 years and older) with fixed appliances undergoing orthodontic treatment.
  • Signed declaration of consent by the patient

Exclusion Criteria:

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

    • obesity:

  • body mass index (BMI) > 30 kg/m² (weight and height will be measured)

    • Eating disorder or underweight

  • BMI < 18,5 kg/m² (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

Sites / Locations

  • Department of Orthodontics and Orofacial OrthopedicsRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Lactobacillus reuteri Prodentis®-lozenges

Placebo-lozenges (BioGaia)

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Probing pocket depth (PPD) (4-point-measurement)
The measurement 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.
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.
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.
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.
Systemic cytokine expression
Samples of peripheral whole blood will be taken. Measurement of systemic cytokine concentration in serum (in pg/mL) will be performed using Enzyme-linked immunosorbent assay (ELISA). To analyse systemic inflammation and a possible Th1-/Th2- or Th-17 shift, cytokines representing the Th1-/Th-2/Th-17 cytokine profile (e.g. TNF, Interferon-Gamma,Interleukin 10) will be measured.
Cellular immunity
Samples of peripheral whole blood will be taken.Composition of immunoregulatory cells in the mononuclear cell fraction (MNC) will be analysed using samples of peripheral blood and MNC isolation. The cellular immune status will be analysed quantitatively (in %: relative percentual distribution in the MNC fraction) using fluor-activated cell scanning (FACS). Lymphocyte typing will be performed using an inflammatory Panel: e.g. CD4+ T cells, CD8+ T cells, CD19+ B cells, CD16+/CD56+ NK cells, CD4+/CD25+/CD127low regulatory T cells, CD45RA/CD45RO naive/memory T cells and activated immune cells.

Full Information

First Posted
September 9, 2020
Last Updated
May 17, 2022
Sponsor
University of Erlangen-Nürnberg
Collaborators
BioGaia AB
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1. Study Identification

Unique Protocol Identification Number
NCT04606186
Brief Title
Influence of Probiotics on Clinical Parameters, the Oral Microbiome and the Immune System During an Orthodontic Treatment in Adult Patients
Official Title
Influence of Probiotics on Clinical Parameters, the Oral Microbiome and the Immune System During an Orthodontic Treatment in Adult Patients: a Prospective, Double-blind, Randomized, Clinical Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 19, 2020 (Actual)
Primary Completion Date
November 1, 2023 (Anticipated)
Study Completion Date
November 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Erlangen-Nürnberg
Collaborators
BioGaia AB

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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 our 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, systemic inflammation and prevent a dysbiosis of the oral microbiome.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gingivitis, Periodontal Inflammation, Orthodontic Appliance Complication
Keywords
Orthodontics, Inflammation, Microbiome, Probiotics

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Monocentric, randomized, double-blind, placebo-controlled, clinical study
Masking
ParticipantInvestigator
Masking Description
Study participants, meeting the inclusion criteria and not fulfilling the exclusion criteria, will be assigned to the study group or to the control group using a randomization plan. Randomization plan will be generated by the Center for Clincal Studies of the University Hospital of Erlangen. The lab manager will prepare storage boxes, in which exactly 168 lozenges will be stored. Half of the boxes will contain test-lozenges (study group), half or them will contain placebo-lozenges (control group). The storage boxes for the test and the placebo group will be identical and blinded. The storage boxes will be labelled with pseudonyms in accordance to the randomization plan generated by the Center for Clinical Studies. Therefore, study participants will not have knowledge of the group affiliation. The collection of the samples and the measuring of the clinical parameters will be performed by one orthodontist, who will be blinded to the randomization of the study participants.
Allocation
Randomized
Enrollment
34 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Lactobacillus reuteri Prodentis®-lozenges
Arm Type
Active Comparator
Arm Title
Placebo-lozenges (BioGaia)
Arm Type
Placebo Comparator
Intervention Type
Dietary Supplement
Intervention Name(s)
Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289)
Intervention Description
Supplementary intake of Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289) 2 times per day for 12 weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo-lozenges (BioGaia)
Intervention Description
Placebo-lozenges (BioGaia)
Primary Outcome Measure Information:
Title
Gingival Index (GI)
Description
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.
Time Frame
Baseline to week 4 of intake
Secondary Outcome Measure Information:
Title
Probing pocket depth (PPD) (4-point-measurement)
Description
The measurement 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.
Time Frame
Baseline till 12 months after insertion of appliance
Title
Modified Plaque Index (MPI)
Description
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.
Time Frame
Baseline till 12 months after insertion of appliance
Title
Local cytokine expression
Description
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.
Time Frame
Baseline till 12 months after insertion of appliance
Title
Oral microbiome
Description
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.
Time Frame
Baseline till 12 months after insertion of appliance
Title
Systemic cytokine expression
Description
Samples of peripheral whole blood will be taken. Measurement of systemic cytokine concentration in serum (in pg/mL) will be performed using Enzyme-linked immunosorbent assay (ELISA). To analyse systemic inflammation and a possible Th1-/Th2- or Th-17 shift, cytokines representing the Th1-/Th-2/Th-17 cytokine profile (e.g. TNF, Interferon-Gamma,Interleukin 10) will be measured.
Time Frame
Baseline till 12 months after insertion of appliance
Title
Cellular immunity
Description
Samples of peripheral whole blood will be taken.Composition of immunoregulatory cells in the mononuclear cell fraction (MNC) will be analysed using samples of peripheral blood and MNC isolation. The cellular immune status will be analysed quantitatively (in %: relative percentual distribution in the MNC fraction) using fluor-activated cell scanning (FACS). Lymphocyte typing will be performed using an inflammatory Panel: e.g. CD4+ T cells, CD8+ T cells, CD19+ B cells, CD16+/CD56+ NK cells, CD4+/CD25+/CD127low regulatory T cells, CD45RA/CD45RO naive/memory T cells and activated immune cells.
Time Frame
Baseline till 12 months after insertion of appliance
Other Pre-specified Outcome Measures:
Title
Adverse events
Description
Collection of adverse events
Time Frame
Baseline till 12 months after insertion of appliance

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Adults (18 years and older) with fixed appliances undergoing orthodontic treatment. Signed declaration of consent by the patient Exclusion Criteria: • Systemic or metabolic disease that are related to gingivitis or (e.g. diabetes) or could possibly influence the oral microbiome • obesity: body mass index (BMI) > 30 kg/m² (weight and height will be measured) • Eating disorder or underweight BMI < 18,5 kg/m² (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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Corinna Lesley Seidel, Dr.
Phone
++49-09131-85-45667
Email
corinna.boeck@uk-erlangen.de
First Name & Middle Initial & Last Name or Official Title & Degree
Lina Gölz, Prof. Dr.
Phone
++ 49 (0)9131 85-33643
Email
lina.goelz@uk-erlangen.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Corinna Lesley Seidel, Dr.
Organizational Affiliation
Department of Orthodontics and Orofacial Orthopedics
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Lina Gölz, Prof.Dr.
Organizational Affiliation
Department of Orthodontics and Orofacial Orthopedics
Official's Role
Study Director
Facility Information:
Facility Name
Department of Orthodontics and Orofacial Orthopedics
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Corinna Lesley Seidel
Phone
+49 (0)91318545667
Ext
091318545667
Email
corinna.seidel@uk-erlangen.de
First Name & Middle Initial & Last Name & Degree
Lina Gölz, Prof.
Phone
+ 49 (0)9131 85-33643
Email
lina.goelz@uk-eralngen.de
First Name & Middle Initial & Last Name & Degree
Corinna L Seidel, Dr.

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35477563
Citation
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.
Results Reference
derived

Learn more about this trial

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

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