Effect of MI Paste Plus™ on Streptococcus Mutans and White Spot Lesions in Fixed Orthodontics
NCT ID: NCT07244991
Last Updated: 2025-12-19
Study Results
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Basic Information
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NOT_YET_RECRUITING
NA
200 participants
INTERVENTIONAL
2025-12-31
2027-11-30
Brief Summary
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Fixed orthodontic appliances complicate oral hygiene by creating retention areas that favor bacterial colonization and alter microbial balance. These conditions increase plaque accumulation and Streptococcus mutans (S. mutans) proliferation in saliva and plaque. The frequent low-pH environment favors aciduric bacteria such as S. mutans and lactobacilli, promoting enamel demineralization and formation of white spot lesions (WSLs) or cavitations. WSLs appear as opaque white areas due to subsurface mineral loss, mainly in the gingival third of the crown. They may develop as early as one month after bracket placement, while in patients without appliances, progression occurs after at least six months. Increased S. mutans levels have been reported as early as six weeks after treatment start. Risk factors include poor brushing, lack of floss or rinse use, time since last cleaning, and presence of caries or lesions.
Intervention MI Paste Plus (GC, Japan) is a remineralizing cream with 0.20% sodium fluoride (900 ppm) and 10% CPP-ACP (RECALDENT™), providing calcium and phosphate stabilized by casein phosphopeptides. It has antibacterial and remineralizing effects, suitable during or after orthodontic treatment to prevent or reduce WSLs.
Objective To evaluate whether MI Paste Plus during fixed orthodontic treatment reduces S. mutans counts in saliva and/or WSL incidence.
Study Design A prospective, triple-blind, randomized clinical trial, approved by the Ethics Committee of the Ministry of Health of Albania and the Ethics Committee for Human Research of Universidad Cardenal Herrera CEU, Spain.
The study will include 200 patients (100 per group) from two orthodontic clinics in Tirana, Albania. Participants will be stratified by age, risk level, and appliance type, then randomized by third parties.
Outcome Measures Primary variables: S. mutans counts in saliva and number of WSLs after 3 months.
Standardized saliva collection, culturing, and bacterial quantification ensure consistency. Clinical assessments will be performed at 1 and 3 months using QRay Cam Pro (Inspektor Systems, Netherlands) for quantitative fluorescence and ICDAS for visual inspection.
Data will be analyzed using SPSS/R Commander software.
Detailed Description
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Fluoride remains the most validated anti-caries agent, and the combination of fluoride with casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) enhances remineralization by maintaining calcium and phosphate in bioavailable form. MI Paste Plus (GC Corporation, Japan) is a topical cream containing 10% CPP-ACP and 0.20% sodium fluoride (≈900 ppm F-), which releases calcium, phosphate, and fluoride ions that penetrate enamel, support remineralization, and inhibit bacterial ATPase activity. Although promising, further rigorously designed, adequately powered randomized clinical trials are needed to determine whether MI Paste Plus reduces salivary S. mutans levels and prevents WSLs during early orthodontic treatment. This doctoral research project aims to fill this gap.
The main objectives are to determine whether daily use of MI Paste Plus alters salivary S. mutans counts after one and three months of fixed orthodontic treatment and whether it prevents or reduces the incidence and severity of WSLs during the same period. Secondary objectives include assessing the relationship between oral hygiene risk status and baseline S. mutans levels or WSL prevalence, and examining whether age, hygiene risk, or appliance type modifies these outcomes. Null hypotheses state that MI Paste Plus does not significantly affect S. mutans levels or WSL development and that age, hygiene level, and appliance type do not modify these results.
This prospective, triple-blind, parallel-group randomized controlled clinical trial will take place in two private orthodontic polyclinics in Tirana, Albania. Ethical approval has been obtained from the Ministry of Health of Albania (Report No. 66/18, April 4, 2024) and from Universidad Cardenal Herrera CEU (May 12, 2025). All procedures comply with the Declaration of Helsinki, Good Clinical Practice, GDPR, the Spanish LOPD, and Albanian data protection law.
A sample of 200 patients (100 per group) will provide \>90% power at α = 0.05 to detect moderate between-group differences, allowing for 10% attrition. Eligible participants will be 5-45 years old, beginning fixed orthodontic treatment, able to comply with procedures, and providing informed consent or assent. Exclusion criteria include systemic conditions affecting salivary flow, antimicrobial use within four weeks, allergies to milk proteins or fluoride, extensive restorations preventing enamel evaluation, or inability to attend follow-ups.
Participants will be stratified by age (≤15 or \>15 years), oral hygiene risk (good or poor), and appliance type, then randomized 1:1 using a computer-generated list prepared by the study statistician. Allocation concealment will use sealed opaque envelopes and coded containers prepared by an independent hygienist. Test and placebo gels are identical in appearance, texture, and packaging. Participants, clinical evaluators, and microbiologists will remain blinded until data lock.
The test group will apply MI Paste Plus nightly for three months after toothbrushing. The control group will apply an inactive bioadhesive gel in the same manner. All participants will continue brushing with fluoridated toothpaste. Adherence will be monitored by daily logs and weighing returned containers.
Assessments occur at baseline (T0), one month (T1 ± 7 days), and three months (T2 ± 14 days). Clinical evaluation of WSLs will be performed using ICDAS. Teeth will be cleaned and dried for approximately five seconds using compressed air to enhance visibility of early changes. A dental operating light, mirror, and blunt probe will be used to classify surfaces from 0 to 6. Surfaces with ICDAS 0 at baseline will be considered sound; those that become ICDAS 1 or 2 at follow-up will be classified as new WSLs. For surfaces with ICDAS 1-2 at baseline, changes over time will indicate progression, stability, or improvement.
Quantitative Light-Induced Fluorescence (QLF™) imaging using the Q-Ray Cam Pro (Inspektor Systems, Netherlands) will complement ICDAS. QLF detects demineralized enamel as dark areas due to fluorescence loss and identifies porphyrin-producing bacterial activity as red/orange fluorescence. White-spot analysis will be performed in the software by activating the White Spot Analysis wizard. The system automatically generates several quantitative parameters, including ΔF (% fluorescence loss), ΔF max, ΔF Average, lesion area (WS Area), and porphyrin fluorescence metrics (ΔR, ΔR max, ΔR area). Although all parameters support clinical interpretation, only ΔF (%) will serve as a registered outcome measure. Negative ΔF values indicate demineralization, while changes in ΔF, WS Area, and ΔR patterns over time allow detection of new lesions and assessment of whether existing lesions progress, stabilize, or remineralize.
Stimulated saliva samples will be collected at least two hours after eating or brushing, refrigerated at 4 °C, and processed within 24 hours. Serial dilutions will be plated on TYCSB medium and incubated anaerobically for 72 hours. Colonies will be subcultured, identified using API 20 Strep, and quantified using standard CFU calculations. Two microbiologists will count plates independently.
Primary outcomes include salivary S. mutans counts and the presence, number, and severity of WSLs based on ICDAS and QLF ΔF values at T1 and T2. Secondary outcomes include plaque index, DMFT/DMFS, and associations with age, hygiene risk, and appliance type. Analyses will follow the intention-to-treat principle. Appropriate parametric or nonparametric tests and mixed-effects models will be used. Missing data will be addressed using multiple imputation.
All data will be recorded on paper CRFs and double-entered into a secure database. Calibration of ICDAS scoring, QLF imaging, and microbiological procedures will occur every six months. Adverse events are expected to be minor. Participants may withdraw at any time. Data confidentiality will follow GDPR, LOPD, and Albanian privacy regulations.
The preparatory phase is 90% complete, including protocol finalization, equipment procurement, staff training, and validation of all clinical and laboratory procedures. Recruitment will occur from November 2025 to June 2027, followed by analysis and dissemination. Results will be submitted to peer-reviewed journals in orthodontics, preventive dentistry, and microbiology, and presented at major conferences. A plain-language summary will be provided to participants, and anonymized datasets may be shared upon request under data-sharing agreements.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
TRIPLE
Study Groups
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Experimental: MI Paste Plus
Participants assigned to the experimental group will apply MI Paste Plus (GC Corporation, Japan) once daily at night after toothbrushing for three months. The product contains casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and 0.20% sodium fluoride (≈900 ppm F-). Application is performed using a clean finger or applicator, avoiding eating, drinking, or rinsing for at least 30 minutes afterward. The goal is to evaluate the preventive effect of MI Paste Plus on Streptococcus mutans levels and enamel white-spot lesions during fixed orthodontic treatment.
MI Paste Plus (CPP-ACP with Sodium Fluoride)
Participants in the experimental arm will apply MI Paste Plus once daily at night after toothbrushing for three months. MI Paste Plus is a water-based topical dental cream containing 10% casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and 0.20% sodium fluoride (900 ppm F-). The product is applied using a clean finger or applicator and left undisturbed for at least 30 minutes. The intervention aims to reduce Streptococcus mutans counts and prevent enamel demineralization (white-spot lesions) during fixed orthodontic treatment.
Placebo Comparator: Bioadhesive Gel without Active Ingredients
Participants in the control group will use an identical-appearing bioadhesive oral gel without active ingredients, applied once daily at night after toothbrushing for three months. The gel has the same texture, color, and packaging as MI Paste Plus and serves as the placebo control. Application instructions are identical to those of the experimental group.
Bioadhesive Oral Gel (Placebo)
Bioadhesive oral gel without active ingredients, identical in appearance to MI Paste Plus, applied once daily for three months under the same conditions to maintain blinding.
Interventions
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MI Paste Plus (CPP-ACP with Sodium Fluoride)
Participants in the experimental arm will apply MI Paste Plus once daily at night after toothbrushing for three months. MI Paste Plus is a water-based topical dental cream containing 10% casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and 0.20% sodium fluoride (900 ppm F-). The product is applied using a clean finger or applicator and left undisturbed for at least 30 minutes. The intervention aims to reduce Streptococcus mutans counts and prevent enamel demineralization (white-spot lesions) during fixed orthodontic treatment.
Bioadhesive Oral Gel (Placebo)
Bioadhesive oral gel without active ingredients, identical in appearance to MI Paste Plus, applied once daily for three months under the same conditions to maintain blinding.
Eligibility Criteria
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Inclusion Criteria
* Indication for fixed orthodontic treatment, either with fixed auxiliary appliances (including orthopedic devices) or brackets with or without auxiliary components.
* General good health with no systemic diseases affecting oral health.
Exclusion Criteria
* Presence of active untreated dental caries at baseline.
* Antibiotic therapy within the previous two months.
* Previous diagnosis of molar-incisor hypomineralization (MIH).
* History of immunosuppression.
* Iron-deficiency anemia or other clinically relevant hematological disorders.
* Parafunctional habits such as lip sucking or finger sucking.
* Use of any type of dental prosthesis.
* Smoking or tobacco use.
* Documented allergy to nickel.
* Requirement for orthodontic treatment using removable appliances or clear aligners.
5 Years
45 Years
ALL
Yes
Sponsors
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Beaty Dent
OTHER
Institute of Public Health, Albania
OTHER_GOV
Cardenal Herrera University
OTHER
Responsible Party
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Santiago Arias de Luxán
Professor of Orthodontics
Principal Investigators
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Santiago Arias de Luxán, DMD, PhD
Role: PRINCIPAL_INVESTIGATOR
Universidad CEU Cardenal Herrera - Facultad de Ciencias de la Salud
Locations
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Beaty Dent
Tirana, Albania, Albania
Happy Dent
Tirana, Albania, Albania
Countries
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Central Contacts
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Facility Contacts
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Shirli Kelmendi, DMD
Role: primary
Manola Kelmendi, DMD, PhD
Role: backup
Enida Petro, DMD, PhD
Role: primary
Manola Kelmendi, DMD, PhD
Role: backup
References
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Wan AK, Seow WK, Walsh LJ, Bird PS. Comparison of five selective media for the growth and enumeration of Streptococcus mutans. Aust Dent J. 2002 Mar;47(1):21-6. doi: 10.1111/j.1834-7819.2002.tb00298.x.
Maret D, Marchal-Sixou C, Vergnes JN, Hamel O, Georgelin-Gurgel M, Van Der Sluis L, Sixou M. Effect of fixed orthodontic appliances on salivary microbial parameters at 6 months: a controlled observational study. J Appl Oral Sci. 2014 Jan-Feb;22(1):38-43. doi: 10.1590/1678-775720130318.
Robertson MA, Kau CH, English JD, Lee RP, Powers J, Nguyen JT. MI Paste Plus to prevent demineralization in orthodontic patients: a prospective randomized controlled trial. Am J Orthod Dentofacial Orthop. 2011 Nov;140(5):660-8. doi: 10.1016/j.ajodo.2010.10.025.
Related Links
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Official website of Universidad Cardenal Herrera CEU, the academic institution overseeing the doctoral research project.
Other Identifiers
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CEEI25_585-Cardenal Herrera
Identifier Type: -
Identifier Source: org_study_id