MI Varnish and MI Paste Plus in a Caries Prevention and Remineralization Study

Study Overview
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Brief Summary
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The objective of this clinical study is to evaluate the efficacy of multiple applications of MI Varnish in combination with MI Paste Plus in caries protection and remineralization in comparison to the use of a control (Crest 1,100ppm Fluoride tooth paste, Fluoride rinse recommendation) in orthodontic patients in a randomized, single blind, prospective, controlled clinical trial over 12 months. The effect will be measured by white spot lesion regression and prevention as lesion count. Lesions will be scored using the Enamel Decalcification Index (EDI) area evaluation scheme (primary outcome), International Caries Detection and Assessment System (ICDAS), the caries lesion activity criteria (Nyvad criteria; Bente Nyvad, Scandinavian Researcher), and Quantitative Light Fluorescence (QLF, Inspektor Pro, Netherlands)/SOPROLIFE (SOPROLIFE fluorescence camera system, Acteon, France) evaluation in maxillary and mandibular anterior teeth with orthodontic brackets in treatment and control groups.

Detailed Description
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The study is designed as randomized, single blind, prospective, clinical trial over 12 months. The subjects for this study will be recruited from the University of California at San Francisco UCSF, School of Dentistry, Orthodontic Clinic. Participants in the study will be patients, who are in orthodontic treatment or will start orthodontic treatment; subjects must have full fixed appliances, with brackets bonded to the buccal surfaces of the maxillary and mandibular incisors, canines and first bicuspids. Subjects will be of moderate or high caries risk according to Caries Risk Assessment and ATP (Adenosine triphosphate) bacteria testing. Subjects will present with at least two active white spot lesions on his/her anterior teeth at the start of the study. The age limitation is ≥ 11 years. The subjects will be randomly assigned to 1) Experimental group: MI Varnish and MI Paste Plus or 2) Control standard of care group: 1,100 ppm Fluoride tooth paste and recommendation to use OTC (Over-the-counter) Fluoride-rinse in the evening at home. The clinical study investigator will evaluate the labial/buccal surfaces of upper and lower anterior teeth (first bicuspid to first bicuspid) for white spot lesions (WSL) at baseline and at the end of 3, 6, and 12 months. Newly formed lesions and changes in existing white spot lesions will be documented (using Enamel Decalcification Index (EDI), ICDAS II, light digital photographs and blue fluorescence photography SOPROLIFE and QLF- Quantitative Light Fluorescence). All subjects will receive one professional tooth cleaning at baseline and at each other evaluation office visit to allow WSL evaluation (cleaning with ultrasonic device, and prophylaxis brush) and treatment application.

Official Title
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MI Varnish and MI Paste Plus in a Caries Prevention and Remineralization Study

Conditions
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Dental White Spots, Dental Caries

Intervention / Treatment
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* Drug: CPP-ACP 5% sodium fluoride varnish & 900ppm fluoride paste
* Drug: 1,100pm F-toothpaste and 0.5%NaF rinse


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 11 or older, good health, either gender present with at least two active white spot lesions on his/her anterior teeth at the start of the study have a moderate or high caries risk according to CAMBRA (Caries Management By Risk Assessment) rules require at least 12 additional months of full fixed appliance therapy from the time they are recruited for the study able to cooperate for treatment in the dental chair and follow at-home instructions have an understanding of the study willing to comply with all study procedures and protocols patient participant is able to provide written informed consent in English; if the participant is a minor, the parent/guardian is able to provide written informed consent in English and the patient participant is able to provide written assent in English patient participant or if a minor, the parent/guardian, is willing to sign the Authorization for Release of Personal Health Information and Use of Personally Unidentified Study Data for Research form; data will only be used for research verifiable records of bonding with Transbond Plus Self-Etching Primer (3M Unitek, Monrovia, CA) and Transbond Light Cure Adhesive or similar products verifiable records that ProSeal has not been applied at any time during the orthodontic treatment Exclusion Criteria: untreated cavitated lesions extensive composite fillings on buccal surfaces of front teeth/first bicuspids or more than one dental crown on front teeth/first bicuspids has sealants or fluoride releasing cements on the buccal surface of the anterior teeth in-office fluoride treatment in the last three months history of using any products containing CCP-ACP (casein phosphopeptides and amorphous calcium phosphate; MI paste, chewing gums or candies, etc.), prescription Fluoride products, and Chlorhexidine use in the last three months intrinsic or extremely heavy extrinsic staining any signs of fluorosis in the dentition any signs of morphologic/anatomical/developmental deviations in the teeth previous history of in office bleaching treatment subject not willing to stop the use of any other oral hygiene product than those prescribed/suggested has underlying systemic disease which could alter enamel composition or formation suffering from systemic diseases, significant past or medical history with conditions that may affect oral health or oral flora (i.e. diabetes, HIV, heart conditions that require antibiotic prophylaxis) use of medication causing dry mouth (extreme high caries risk) subject is pregnant or lactating milk protein allergy any illness/condition that the investigator feels will affect the study outcome will leave the area and will not be available for recall visits subjects who are not willing to inform us about prospective visits of other dentist and will not allow us to discuss treatment with those dentist subjects who are not willing to refrain from any additional professional tooth cleaning or any additional Fluoride application.

Ages Eligible for Study
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Minimum Age: 11 Years

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MI Paste & MI Varnish<br>MI past will be applied by the patient every night; MI varnish will be applied every three months in the office | Drug: CPP-ACP 5% sodium fluoride varnish & 900ppm fluoride paste<br>* MI Paste & MI Varnish- in-office: varnish application once every 3 months; at baseline, at the end of month 3, 6, and 9 (4 applications) - at-home: brushing with regular 1,100ppm F-toothpaste, 2x per day and MI Paste Plus, home application after brushing in the evening; 3-5 minutes with in-home application tray<br>|
| Active Comparator: Standard of Care<br>Subjects will use at home regal toothpaste every night and F-mouth rinse as recommended | Drug: 1,100pm F-toothpaste and 0.5%NaF rinse<br>* Standard of care at-home: Crest tooth brushing 2x per day - (recommendation OTC Fluoride-rinse in the evening at home 1x per day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in White Spot Lesions Count - Enamel Decalcification Index (EDI) | The area evaluation scheme of the Enamel Decalcification Index (EDI) divides the buccal surface of each tooth into 4 quadrants and then registers the possible existence of a white spot lesion (decalcification) in each of these 4 quadrants. For each quadrant the lesion can be scaled as: 0 = no decalcification, 1 = decalcification covering <50% of the area, 2 = decalcification covering > 50% of the area, 3 = decalcifications covering 100% of the area or severe decalcification with cavitation. Thus, for each tooth the value can range between 0 and 12. 16 teeth per subject were evaluated, for each subject the value of each tooth was added - thus the range per one subject can be between 0 and 192. A mean over all participants in one group was calculated. A higher score means a worse outcome. | Baseline and 12-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in International Caries Detection and Assessment System (ICDAS II) to Score for Smooth Surfaces White Spot Lesions (WSL) | The International Caries Detection and Assessment System (ICDAS II) is a standardized method of caries lesion assessment.The score is based on apparent lesion severity, with scores from 0 to 6.The buccal surface of each tooth was divided into 4 quadrants, and for each quadrant a score was assigned with ICDAS scores: 0 = sound, 1 = first visual change in enamel, after air drying, 2 = distinct demineralization visual change in enamel, 3 = localized enamel breakdown due to caries with no visible dentin, 4 = surface with underlying dark shadow from dentin with or without enamel breakdown, 5 = distinct cavity with visible dentin, 6 = extensive cavity with visible dentin. The ICDAS scores were calculated as the sum of the highest ICDAS scores assigned to each examined tooth per subject. 16 teeth per subject were evaluated, thus, for each subject the value can range between 0 and 96. A mean over all participants in one group was calculated. A higher score means a worse outcome. | Baseline and 12-months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention