NCT07244991

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P75+ for not_applicable

Timeline
18mo left

Started Jan 2026

Typical duration for not_applicable

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress19%
Jan 2026Nov 2027

First Submitted

Initial submission to the registry

November 14, 2025

Completed
10 days until next milestone

First Posted

Study publicly available on registry

November 24, 2025

Completed
1 month until next milestone

Study Start

First participant enrolled

January 4, 2026

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2027

Expected
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2027

Last Updated

March 27, 2026

Status Verified

December 1, 2025

Enrollment Period

1.4 years

First QC Date

November 14, 2025

Last Update Submit

March 24, 2026

Conditions

Keywords

MI Paste PlusRemineralizationStreptococcus mutansWhite Spot LesionsFixed Orthodontic AppliancesQuantitative Light-Induced FluorescenceRandomized Controlled TrialTriple-Blind StudyAlbaniaCEU Cardenal Herrera University

Outcome Measures

Primary Outcomes (1)

  • Change in salivary Streptococcus mutans count (log₁₀ CFU/mL)

    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.

    Baseline, 1 month, 3 months

Secondary Outcomes (2)

  • 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

Study Arms (2)

Experimental: MI Paste Plus

EXPERIMENTAL

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.

Other: MI Paste Plus (CPP-ACP with Sodium Fluoride)

Placebo Comparator: Bioadhesive Gel without Active Ingredients

PLACEBO COMPARATOR

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.

Other: Bioadhesive Oral Gel (Placebo)

Interventions

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.

Experimental: MI Paste Plus

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.

Placebo Comparator: Bioadhesive Gel without Active Ingredients

Eligibility Criteria

Age5 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Beaty Dent

Tirana, Albania, 1001, Albania

RECRUITING

Happy Dent

Tirana, Albania, 1001, Albania

NOT YET RECRUITING

Related Publications (3)

  • 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.

    PMID: 12035953BACKGROUND
  • 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.

    PMID: 24626247BACKGROUND
  • 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.

    PMID: 22051486BACKGROUND

Related Links

MeSH Terms

Conditions

Dental CariesTooth Demineralization

Interventions

casein phosphopeptide-amorphous calcium phosphate nanocomplexSodium Fluoride

Condition Hierarchy (Ancestors)

Tooth DiseasesStomatognathic Diseases

Intervention Hierarchy (Ancestors)

FluoridesHydrofluoric AcidFluorine CompoundsInorganic ChemicalsSodium CompoundsCariostatic AgentsBiomedical and Dental MaterialsManufactured MaterialsTechnology, Industry, and Agriculture

Study Officials

  • Santiago Arias de Luxán, DMD, PhD

    Universidad CEU Cardenal Herrera - Facultad de Ciencias de la Salud

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Santiago Arias de Luxán, DMD, PhD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
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.
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: Participants will be randomly assigned in a 1:1 ratio to one of two parallel groups: the experimental group using MI Paste Plus (containing CPP-ACP and fluoride) and the control group using a bioadhesive placebo gel without active ingredients. Both groups will be followed concurrently for three months under identical clinical and microbiological evaluation schedules. The study follows a triple-blind design (participant, investigator, and outcome assessor) with stratified randomization by age, oral-hygiene risk, and type of orthodontic appliance.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Orthodontics

Study Record Dates

First Submitted

November 14, 2025

First Posted

November 24, 2025

Study Start

January 4, 2026

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

November 1, 2027

Last Updated

March 27, 2026

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share

Individual participant data will not be publicly available to protect patient privacy, but de-identified data may be provided by the corresponding author upon reasonable request after publication.

Locations