Prospective Randomized Controlled Trial for Prevention of Demineralization During Fixed Orthodontic Treatment

Study Overview
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Brief Summary
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Treatment with fixed orthodontic appliances is often associated with pain, which poses great challenges in the efficient brushing of the teeth thus making the teeth more vulnerable to plaque formation. Treatment duration with fixed orthodontic appliances usually extends to 18 months or even longer in some cases. This prolonged vulnerability to plaque formation frequently leads to demineralization of teeth. There is also an increase in the number of plaque retentive sites due to the fixed appliances, leading to a rapid change in the bacterial composition of the dental plaque, particularly in the number of acidogenic bacteria. The resulting enamel decalcification is also known as white spot lesions (WSLs), which is an early sign of demineralization of enamel. Enamel WSLs (EWSLs) can be observed even as early as four weeks from the start of fixed orthodontic treatment. The occurrence of EWSLs adjacent to the orthodontic brackets ranges from 15 to 85%. The incidence of EWSLs development is higher in orthodontic patients as compared to the development of similar lesions in non-orthodontic patients. These EWSLs are not aesthetically pleasing and is certainly unacceptable when it develops during fixed orthodontic treatment that is usually performed in patients who often seek such treatment to improve their aesthetics. Additionally, even if the outcome of fixed orthodontic treatment is superior from well-aligned teeth, aesthetics can be greatly compromised with EWSLs. Therefore, the prevention of such lesions is an important concern for orthodontists. Though professionally applied topical fluoride varnish helps in remineralization of EWSLs, an adequate supply of calcium and phosphate ions is essential for remineralization. Therefore, EWSLs on maxillary teeth could be prevented and remineralized by the use of advanced novel topical fluoride varnish with added calcium and phosphate-based delivery system.

Detailed Description
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Fluoride is proven caries preventive and therapeutic agent. It helps in the remineralization of early enamel caries lesions and subsequently increases its resistance to dissolution by acids produced by cariogenic microflora. Topical fluoride varnish was introduced in the 1960s. The Food and Drug Administration (FDA) in the USA approved the use of fluoride varnishes for dentistry in 1994 and presently fluoride varnish is the most commonly used professionally applied topical fluoride agent. The most popular topical fluoride varnish is Duraphat®, which contains 5% NaF varnish (2.2% Fluoride). The greatest advantage of topical fluoride varnish is its ability to adhere to tooth tissues for a longer period of time that enables improved fluoride uptake. It allows the continuous release of fluoride ions into enamel, dentine, plaque, and saliva. Additionally, the application of topical fluoride varnish is a simple procedure and does not require great patient co-operation. Topical fluoride varnish application has been reported to exhibit substantial caries inhibiting effect in both permanent and primary teeth. Among the various forms of fluoride products, such as gels, varnishes, foams, mouth- rinses, and toothpastes, varnishes do not rely on patient compliance and cooperation. The major advantage of varnishes is high retention followed by gradual release of fluoride over an extended time period, which leads to low concentrations in the liquid plaque-enamel interface. The use of fluoride diminishes demineralization and promotes remineralization, thereby balancing the process of caries formation. A recent Cochrane review has revealed moderate evidence for the prevention of EWSLs during fixed orthodontic treatment by fluoride varnish application every six weeks at the time of orthodontic review, but this finding is based on a single study. Therefore, the quality of the evidence found is moderate and the review recommendations state that additional well- conducted research is required in this area. Caries preventive and inhibiting effect of topical fluoride therapy depends on an adequate supply of calcium and phosphate ions. Though calcium and phosphate ions are supplied naturally by saliva, the concentration of such ions is low (even lower in patients suffering from reduced salivary flow). Low concentration of salivary calcium and phosphate ions leads to a mineral deposition only at the surface of the enamel as a result of a low ion concentration gradient. The deposition of minerals at the surface of enamel alone may not improve the structural properties of the deeper part of the early-stage or incipient caries lesions. This has led to the introduction of calcium phosphate-based delivery systems containing high concentrations of calcium phosphate such as tri-calcium phosphate (TCP). Tri-calcium phosphate (TCP) is a product resulting from ball milling beta-tri-calcium phosphate with sodium lauryl sulphate. ClinproTM white varnish (3M ESPE, St Paul, MN, USA), which contains TCP and NaF, is a commercially available topical fluoride varnish, which claims that the protective fumaric acid barrier facilitates co-existence of calcium and fluoride ions, however, during storage, the unwanted reaction between the ions is prevented. The protective barrier breaks upon contact with saliva, releasing the ions for effective remineralization of the tooth. At present there is no clinical study to prove the superior EWSLs-preventive effect of this newer NaF varnish with TCP when compared to conventional topical NaF varnish in patients undergoing fixed orthodontic treatment.

Official Title
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A Prospective Randomized Controlled Trial for Prevention of Enamel White Spot Lesions During Fixed Orthodontic Treatment

Conditions
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Caries,Dental, Demineralization, Tooth, White Spot Lesion

Intervention / Treatment
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* Drug: Fluoride Varnish
* Drug: Fluoride Varnish with tricalcium phosphate
* Other: Oral health education


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects about to undergo multi-bracketed fixed orthodontic treatment will be invited to participate in this study. Exclusion Criteria: History of fixed orthodontic treatment Presence of any developmental defects of enamel (DDE) on labial surfaces of teeth Presence of any dental anomalies or direct/indirect labial restorations on teeth History of long-term antibiotic usage Presence of untreated cavitated lesions Plaque level greater than 25% Patients requiring complicated orthognathic surgeries
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized controlled trial with three parallel groups. In the proposed study, individual participants, and not parts of the mouth, will serve as the unit of randomization. This approach unlike a split-mouth design will eliminate the problems of cross-contamination.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Standard of care<br>Control will receive standard oral hygiene instructions (OHI every three months) | Other: Oral health education<br>* Standard oral hygiene instructions every 3 months<br>* Other names: Oral hygiene instructions;|
| Active Comparator: Standard of care + Fluoride varnish<br>Intervention 1 will receive standard OHI and application of topical fluoride varnish containing 5% NaF (Duraphat varnish®, Colgate-Palmolive (UK) Ltd., Guildford, Surrey, UK) every three months | Drug: Fluoride Varnish<br>* Duraphat varnish®, Colgate-Palmolive (UK) Ltd., Guildford, Surrey, UK<br>* Other names: 5% Sodium fluoride varnish;|
| Experimental: Standard of care + Fluoride varnish with Tricalcium phosphate<br>Intervention 2 will receive standard OHI and application of topical fluoride varnish containing 5% NaF + TCP (Clinpro white varnishTM, 3M ESPE, St Paul, MN, USA) every three months | Drug: Fluoride Varnish with tricalcium phosphate<br>* Clinpro white varnishTM, 3M ESPE, St Paul, MN, USA<br>* Other names: 5% Sodium fluoride varnish containing tri-calcium phosphate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Enamel White Spot Lesions index surface scores: Clinical evaluation (Subjective criteria) | Changes in EWSLs surface scores (using Gorelick's index, 1982) among three study groups (evaluated clinically). The Gorelick's index is graded as: 0 (no lesion), 1(moderate lesion), 2 (severe lesion) and 3 (cavitation) with lower score representing good outcome and higher score representing poor outcome. | 24 months | 
| Change in Enamel White Spot Lesions index surface scores: Photographic evaluation (Subjective criteria) | Changes in EWSLs surface scores (using Gorelick's index, 1982) among three study groups (evaluated photographically). The Gorelick's index is graded as: 0 (no lesion), 1(moderate lesion), 2 (severe lesion) and 3 (cavitation) with lower score representing good outcome and higher score representing poor outcome | 24 months | 
| Change in Laser fluoroscence values (Objective criteria) | Changes in mean DIAGNOdent scores among three study groups. The DIAGNOdent values (or laser fluorescence values) are visible on the device as digital readings from 0 to 99 with higher readings representing poor outcomes and lower readings representing good outcomes. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enamel White Spot Lesions index surface scores: Clinical evaluation (Subjective criteria) | EWSLs surface scores (using Gorelick's index, 1982) among three study groups (evaluated clinically) | 6 months | 
| Enamel White Spot Lesions index surface scores: Clinical evaluation (Subjective criteria) | EWSLs surface scores (using Gorelick's index, 1982) among three study groups (evaluated clinically) | 12 months | 
| Enamel White Spot Lesions index surface scores: Clinical evaluation (Subjective criteria) | EWSLs surface scores (using Gorelick's index, 1982) among three study groups (evaluated clinically) | 18 months | 
| Enamel White Spot Lesions index surface scores: Photographic evaluation (Subjective criteria) | EWSLs surface scores (using Gorelick's index, 1982) among three study groups (evaluated photographically) | 6 months | 
| Enamel White Spot Lesions index surface scores: Photographic evaluation (Subjective criteria) | EWSLs surface scores (using Gorelick's index, 1982) among three study groups (evaluated photographically) | 12 months | 
| Enamel White Spot Lesions index surface scores: Photographic evaluation (Subjective criteria) | EWSLs surface scores (using Gorelick's index, 1982) among three study groups (evaluated photographically) | 18 months | 
| Laser fluoroscence evaluation (Objective criteria) | Mean DIAGNOdent scores among three study groups | 6 months | 
| Laser fluoroscence evaluation (Objective criteria) | Mean DIAGNOdent scores among three study groups | 12 months | 
| Laser fluoroscence evaluation (Objective criteria) | Mean DIAGNOdent scores among three study groups | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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orthodontics, demineralizatiion, fluoride, Diagnodent