Effect of MI Paste Plus™ on Streptococcus Mutans Counts and White Spot Lesions in Patients With Fixed Orthodontic Appliances: A Triple-Blind Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 200
- 试验地点
- 4
- 主要终点
- Change in salivary Streptococcus mutans count (log₁₀ CFU/mL)
研究概览
简要总结
Background This study is part of a doctoral research project at Universidad Cardenal Herrera CEU (Spain), directed by Prof. Santiago Arias de Luxán and conducted by doctoral candidate Shirli Kelmendi within the PhD program in Translational Medicine.
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.
详细描述
Fixed orthodontic appliances are among the most common treatments in contemporary dentistry, yet they significantly modify the oral environment and create plaque-retentive areas that favor bacterial colonization. Brackets, ligatures, and auxiliary components increase the difficulty of oral hygiene and shift the ecological balance of the dental biofilm, favoring aciduric and acidogenic organisms such as Streptococcus mutans (S. mutans). Repeated exposure of dental plaque to a low pH inhibits acid-sensitive species and promotes S. mutans and lactobacilli, whose metabolic activity produces lactic acid and leads to enamel demineralization. Clinically, this presents as white-spot lesions (WSLs), the earliest visible stage of dental caries. Such lesions may appear within one month of appliance placement, whereas comparable demineralization in patients without orthodontic devices usually requires six months or longer. WSLs compromise esthetics and tooth integrity and may persist after orthodontic treatment ends, making early prevention essential.
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The study is conducted under a triple-blind design. Participants, investigators, and outcome assessors remain unaware of group assignments. Both MI Paste Plus and placebo gels are identical in packaging, texture, and color and are supplied in coded opaque containers prepared by a dental hygienist not involved in patient evaluation or data analysis. The randomization code will be kept sealed until the completion of data collection and statistical analysis.
入排标准
- 年龄范围
- 5 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 5 and 45 years.
- •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.
排除标准
- •Advanced white-spot lesions with untreated dentin involvement.
- •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.
结局指标
主要结局
Change in salivary Streptococcus mutans count (log₁₀ CFU/mL)
时间窗: Baseline, 1 month, 3 months
Stimulated saliva will be collected after ≥2 hours of fasting and oral hygiene abstention, using sterile insulin syringes to obtain 2-3 mL directly from the floor of the mouth. Samples will be refrigerated (4 °C, ≤24h), serially diluted in saline, and 1 µL plated onto TYCSB selective agar for anaerobic incubation at 37 °C for 72 hours. Colonies will be identified morphologically and confirmed with API Strep 20. S. mutans levels (CFU/mL) will be calculated from colony counts and dilution factors and expressed as log₁₀ CFU/mL. The outcome is the change in S. mutans from baseline to 1 and 3 months.
次要结局
- Incidence of new white-spot enamel lesions detected by ICDAS(Baseline, 1 month, 3 months)
- Change in ΔF (%) of white-spot lesions measured by QLF™(Baseline, 1 month, 3 months)
研究者
Santiago Arias de Luxán
Professor of Orthodontics
Cardenal Herrera University