Clinical trial NCT03446690
Conditions: White Spot Lesion Orthodontic Treatment
Keywords: Enamel decalcification
Sponsor: University of Alabama at Birmingham
Start date: 2015-01-01; Completion date: 2016-01-01
Enrollment: 62 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The current study aimed to determine if MI Varnish has an effect in preventing the formation of white spot lesions for patients undergoing orthodontic treatment. 33 subjects were prospectively recruited for the project as the MI Varnish group, with a control group of 29 orthodontically treated subjects who received routine treatment and oral hygiene regimes.Difference in prevention of white spot formation between the control and the study groups were evaluated through photographic records and clinical examination by using the Enamel Decalcification Index (EDI) scores.

Detailed description:
Orthodontists face two common iatrogenic treatment side effects, root resorption and enamel decalcification, with the latter occurring at a much higher frequency. While the processes that lead to enamel demineralization are understood, methods to diminish or perhaps eliminate degradation of enamel surfaces are being searched for. A new product, MI Varnish, is current available and has been shown in some initial case reports to be useful in reducing white spot lesions. It contains a special milk-derived protein RECALDENT TM (CPP-ACP) in which the casein phosphopeptides (CPP) bind to teeth, dentin, and oral mucosa while the amorphous calcium phosphate (ACP) releases calcium and phosphate. The current study aimed to determine if MI Varnish has an effect in preventing the formation of white spot lesions for patients undergoing orthodontic treatment. 33 subjects were prospectively recruited for the project as the MI Varnish group, with a control group of 29 orthodontically treated subjects who received routine treatment and oral hygiene regimes. The study group received the MI Varnish on the day of bracket bonding. Subjects were recalled initially for 4 weeks (twice) and then at 3 monthly intervals. Difference in prevention of white spot formation between the control and the study groups were evaluated through photographic records and clinical examination by using the Enamel Decalcification Index (EDI) scores.

Arms: arm 1: 33 subjects were prospectively recruited for the project in the MI Varnish group. All subjects will be patients seeking orthodontic treatment at the Department of Orthodontics, UAB. MI Varnish were applied on their teeth initially for 4 weeks (twice) and then 3 monthly intervals. arm 2: A control group was comprised of 29 orthodontically treated subjects who received routine treatment and oral hygiene regimes. All subjects will be patients seeking orthodontic treatment at the Department of Orthodontics, School of Dentistry, University of Alabama at Birmingham. No intervention for this group.
Interventions: intervention 1: MI Varnish intervention 2: Control group
Intervention descriptions: intervention 1: MI Varnish with RECALDENT™ (CPP-ACP) enhances enamel acid resistance and boosts salivary fluoride levels. This product remains on the teeth longer than other fluoride varnishes and contains high levels of fluoride and calcium released in the oral cavity. The difference is in the RECALDENT™ (CPP-ACP), which makes MI Varnish a natural and unique choice for your patients. Casein phosphopeptides (CPP) naturally occurs in milk casein; Amorphous Calcium Phosphate (ACP), which is found in the RECALDENT™, is also the source of calcium and phosphate. In the oral cavity, CPP binds to oral surfaces such as teeth, dentin, oral mucosa and biofilm. Calcium and phosphate ions are the building blocks for healthy teeth and MI Varnish delivers bioavailable calcium and phosphate ions into the saliva. intervention 2: Participants received routine treatment and oral hygiene regimes. No intervention for this group.

Protocol documents:
Prot_000.pdf: 
Page | 1 
 
Title of Research: 
The Use of MI Varnish for the Prevention and Reduction of White 
Spot Lesions in Orthodontic Treatment   
WIRB Protocol #: 
20120677 
Principal Investigator: 
      Dr. Chung How Kau, BDS, MScD, PhD.   
Document Date:                                  January 1, 2018 
 
 
INTRODUCTION 
 
During the course of orthodontic treatment, the practitioner faces two common iatrogenic 
treatment side effects, root resorption and enamel decalcification, with the latter occurring at a 
much higher frequency.  While the processes that lead to enamel demineralization are understood, 
methods to diminish or perhaps eliminate degradation of enamel surfaces are being searched for.  
Several approaches have been formulated to counteract demineralization of tooth structure.  One 
approach involves patient compliance and consists of in-depth oral hygiene instructions, in-office 
fluoride applications, and at-home fluoride rinses, gels and varnishes.  An alternative approach, 
which possesses potential benefit regardless of patient compliance includes the use of fluoride-
releasing agents, such as composites, glass ionomers, sealants, and elastomeric ties.   
 
Enamel decalcification or white spot formation, is a phenomenon occurring primarily on 
smooth enamel surfaces of teeth, notably within the gingival third of the crown.  Demineralized 
enamel, the precursor to caries formation, can be attributed to fixed orthodontic appliances, and 
prolonged exposure to bacterial plaque.  Bacterial plaque promotes the accumulation of acidic 
byproducts and demineralization that leads to successive changes in the optical properties of 
subsurface demineralized enamel.  Progression to clinically detectable white spot lesions may 
occur as early as one month following the placement of orthodontic appliances.   
 
Over the past thirty years, numerous studies have reported an increase in white spot lesions 
following orthodontic treatment.  While a large portion of the non-orthodontically-treated 
population experiences some form of decalcification, orthodontically-treated patient populations 
have shown both an increase in new lesions and an increase in the severity of preexisting enamel 
opacities.  Approximately, 50 percent of orthodontically-treated patients develop white spot 


Page | 2 
 
lesions in one or more teeth, compared with only 24 percent in those not undergoing orthodontic 
treatment.   
 
Appliance removal halts white spot formation and further elimination of cariogenic factors 
through diligent oral hygiene efforts inactivates incipient lesions, which may undergo regression 
over time.  Complete elimination of lesions is unlikely due to the rapid remineralization of the 
enamel surface with high concentration fluorides, which restrict passage of ions into the deeper 
more affected layers.  Therefore, immediate application of high concentration of fluoride is not 
recommended.  Decreased enamel discolorations may occur with time due to further 
remineralization, but regression is primarily credited to gradual surface abrasion of tooth structure. 
 
Such problems with enamel decalcification in orthodontic patients have influenced 
clinicians to search for a solution to orthodontic-associated demineralization.  Because fluoride 
treatment immediately upon debonding is not advocated, clinicians have proposed fluoride 
treatment and fluoride-releasing materials at the commencement of therapy.  Recommended 
solutions include oral hygiene instruction and reinforcement, fluoridated toothpastes, varnishes 
and mouthwashes, and fluoridated water supply.  Lack of patient compliance hinders these efforts.  
 
A new product, MI Varnish is current available and has been shown in some initial case 
reports to be useful in the reduction of white spot lesions. MI Varnish is a one-of-a-kind product 
that restores minerals and helps you produce saliva. It’s the only dental product with 
RECALDENT TM (CPP-ACP), a special milk-derived protein that’s a breakthrough in oral health 
care in helping to remineralize teeth.  
• 
Strengthens teeth with tooth-replenishing calcium and phosphate  
• 
Releases vital minerals into your mouth when and where they’re needed  
• 
Produces a saliva-like environment that maintains normal acid levels and healthy 
teeth  
• 
Recaldent TM CPP-ACP is milk derived with lactose content less than 0.01%.*  
 
AIM 
To determine if MI Varnish has an effect in preventing the formation of white spot lesions for 
patients undergoing orthodontic treatment. 
 
MATERIALS AND METHODS 


Page | 3 
 
Subjects 
33 subjects were prospectively recruited for the project in the MI Varnish group. These subjects 
were studied against a control group of 29 orthodontically treated subjects who received routine 
treatment and oral hygiene regimes. All subjects will be patients seeking orthodontic treatment at 
the Department of Orthodontics, School of Dentistry, University of Alabama at Birmingham. A 
caries risk assessment (Information attached) will be used to determine the caries risk of all patients 
enrolled in the study. 
 
Varnish Delivery 
The study group received the MI Varnish on the day of bracket bonding. The varnish was delivered 
all around the bracket and left for 15 minutes. Patients did not rinse after they received treatment.   
 
Re-call 
Subjects were recalled at initially for 4 weeks (twice) and then 3 monthly intervals. 
 
EVALUATION OF RESULTS 
The following two forms of evaluations will be carried out: 
(a) Photographic records 
(b) Clinical examination 
 
Photographic records 
Photographic records will be used to determine the improvements in the white spot lesions. A 
standard intra-oral photographic camera will be utilized and the photographs will be taken in a 
light controlled environment and photographs will be captured in a pre-set photographic protocol. 
The Enamel decalcification index (Banks and Richmond) – FIG 1 will be used to determine the 
number of white spot lesions present at each time frame. This method has been used successfully 
by Robertson and Kau et al (American Journal of Orthodontics and Dentofacial Orthopedics – In 
press) 
 
 

SAP_001.pdf: 
 
 
Statistical Analysis Plan 
 
Title of Research: 
The Use of MI Varnish for the Prevention and Reduction of White Spot Lesions in 
Orthodontic Treatment   
WIRB Protocol #: 
20120677 
Principal Investigator: 
      Dr. Chung How Kau, BDS, MScD, PhD.   
Document Date:                                  January 1, 2018 
 
Results and Statistics 
The results will be evaluated in the following manner:  
(1) Difference in prevention of white spot formation between the control and the study groups using the 
EDI scores 
      (2)Standard statistical methods were employed to analyze all data.  
 
 
Data Collection and Database Management 
Data collection, database management, and data analyses were performed by sponsor personnel or its designee. 
Only the sponsor, or its appropriate designee, had access to individual-level patient data collected as part of 
this study, regardless of whether the patient provided informed consent and HIPAA authorization. All 
individual level patient data had identification information removed. 
 
Data Analysis 
 
All measured variables and derived parameters will be tabulated by descriptive statistics.  
For categorical variables summary tables will be provided giving sample size, absolute and relative frequency and 95% 
CI (Confidence Interval) for proportions. 
 
For continuous variables summary tables will be provided giving sample size, arithmetic mean, standard deviation, 
median, minimum and maximum and 95% CI (Confidence Interval) for means of variables.  


 
All tests will be two-tailed, and a p value of 5% or less will be considered statistically significant.  
All statistical analyses will be performed and data appendices will be created using the SAS® system Version 9.1.3 or 
higher.   
The effects of noncompliance, dropouts, and covariates on treatment will be assessed to determine the impact on 
the general applicability of results from this study.   
 
 
 
 
 
Figure 1. Enamel Decalcification Index. Facial surface of each tooth was divided into four areas. A score was 
allocated for each area of each tooth: 0=No decalcification to 3=Decalcifications covering 100% of the area.