GingivitisNCT04598633
Influence of Probiotics on Clinical Parameters, the Oral Microbiome and the Immune System During an Orthodontic Treatment
A study testing Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289) in people with Gingivitis and Orthodontic Appliance Complication, run by University of Erlangen-Nürnberg at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Gingivitis, Orthodontic Appliance Complication
- What is being tested?
- Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteGermany
- Study dates
- 24 Nov 2020to 1 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
UniversityHospitalErlangen-Nurenberg
Erlangen, Bavaria, 91054
Corinna L Seidel, Dr., 091318545667 ext. 091318545667, corinna.seidel@uk-erlangen.de
Lina L Gölz, Prof., 091318533643 ext. 091318545667, lina.goelz@uk-erlangen.de
About this study
Official title: 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.
- Conditions
- Gingivitis, Orthodontic Appliance Complication
- Being tested
- Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289), Placebo-lozenges (BioGaia)
- Keywords
- Orthodontics; Inflammation; Microbiome; Probiotics
- Medical subject headings
- Gingivitis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289)Dietary supplement
Supplementary intake of Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289) 2 times per day for 12 weeks
Placebo-lozenges (BioGaia)Dietary supplement
Placebo-lozenges (BioGaia) 2 times per day for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Lactobacillus reuteri Prodentis®-lozenges | Active comparator | Not described Receives: Dietary Supplement: Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289) |
| Placebo-lozenges (BioGaia) | Placebo comparator | Not described Receives: Dietary Supplement: Placebo-lozenges (BioGaia) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to week 4 of intake
Secondary outcomes (4)
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.
Measured: 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
Measured: Baseline till 12 months after insertion of appliance
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.
Measured: 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.
Measured: Baseline till 12 months after insertion of appliance
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2020
- Study start24 Nov 2020
- Primary completion1 Dec 2022 (estimated)
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GingivitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Monocentric, randomized, double-blind, placebo-controlled, clinical study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Erlangen-Nürnberg
- Sponsor type
- University, hospital or other
- Collaborators
- BioGaia AB
- Responsible party
- Principal investigator, Dr. Corinna Lesley Seidel, University of Erlangen-Nürnberg
- Investigators
- Corinna Lesley Seidel, Dr., Study director, Department of Orthodontics and Orofacial OrthopedicsLina Gölz, Prof.Dr., Study director, Department of Orthodontics and Orofacial Orthopedics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04598633
- Sponsor's protocol ID
- ER-Ortho-Pro-RCT-1
- Status last verified
- May 2022
- First submitted
- 9 Sep 2020
- Last updated
- 18 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 35477563
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Probiotics on Clinical Parameters, the Oral Microbiome and the Immune System During an Orthodontic Treatment: a Prospective, Double-blind, Randomized, Clinical Study
- ClinicalTrials.gov ID
- NCT04598633
- Acronym / sponsor ID
- ER-Ortho-Pro-RCT-1
- Conditions
- Gingivitis, Orthodontic Appliance Complication
- Keywords
- Orthodontics; Inflammation; Microbiome; Probiotics
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- University of Erlangen-NürnbergUniversity, hospital or other
- Collaborators
- BioGaia AB
- Study start
- 24 Nov 2020 (actual)
- Primary completion
- 1 Dec 2022 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 22 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Monocentric, randomized, double-blind, placebo-controlled, clinical study
| Arm | Type | Receives |
|---|---|---|
| Lactobacillus reuteri Prodentis®-lozenges | Active comparator | Dietary Supplement: Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289) |
| Placebo-lozenges (BioGaia) | Placebo comparator | Dietary Supplement: Placebo-lozenges (BioGaia) |
Who may qualify
- Ages
- 12 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Dietary supplement | Lactobacillus reuteri Prodentis®-lozenges |
| Placebo-lozenges (BioGaia)Placebo-lozenges (BioGaia) 2 times per day for 12 weeks | Dietary supplement | Placebo-lozenges (BioGaia) |
Primary outcome
Gingival Index (GI)
Time frame: Baseline to week 4 of intake
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. 1. = Mild inflammation - slight cliange in color and little change in texture. 2. = Moderate inflammation - modcrate glazing, redness,oedema, hypertrophy, bleeding on pressure. 3. = Severe inflammation - marked redness and hypertrophy, tendency to spontaneous bleeding, ulceration.
4 secondary outcomes
Probing pocket depth (PPD) (4-point-measurement)
Time frame: Baseline till 12 months after insertion of appliance
Modified Plaque Index (MPI)
Time frame: Baseline till 12 months after insertion of appliance
Local cytokine expression
Time frame: Baseline till 12 months after insertion of appliance
Oral microbiome
Time frame: Baseline till 12 months after insertion of appliance
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2022.
- Derived from this study: PubMed 35477563Seidel 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Corinna Lesley Seidel, Dr. study director
Department of Orthodontics and Orofacial Orthopedics
Lina Gölz, Prof.Dr. study director
Department of Orthodontics and Orofacial Orthopedics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289) in people with Gingivitis and Orthodontic Appliance Complication, run by University of Erlangen-Nürnberg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Corinna Lesley Seidel, Dr. (++49-09131-85-45667, corinna.boeck@uk-erlangen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gingival Index (GI) (time frame: Baseline to week 4 of intake). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04598633, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2022.