Description

Protocol

Efficacy and Safety Of Topical 10% Povidone-Iodine In Preventing White Spots During Orthodontic Treatment

Design

A triple-blind randomized trial with two arms (10% Povidone Iodine, Placebo) where the primary outcome is the percentage of patients with at least one new white spot lesion on the maxillary anterior teeth at 1 year of follow-up. The secondary outcomes will utilize the ICDAS on the upper and lower anterior teeth, a modified Gingival Index, and Acceptability.

Hypothesis

Participants treated with the test agent will be less likely to develop any enamel decalcification than participants treated with the placebo comparator. Also, the probability of any ICDAS score greater than 0 and mean modified Gingival Index will be lower in the treatment group than in the comparator.

Recruitment/Consent:

The participants will be recruited as they begin treatment. The orthodontic graduate student will briefly present the study and ask if the child/teen and caregiver (parent, guardian) are willing to talk about the study and then, if the child/teen and caregiver are willing, a research assistant will further explain participation and gain informed assent from the child/teen and consent from the parent.

Intervention

Povi-One (10% povidone-iodine) will be applied topically by the graduate student to all tooth surfaces at the consultation appointment (baseline) before the placement of fixed appliances. Povi-one (or control) will be applied again at 3, 6, and 9 months after appliance placement by the graduate student.

Control

The placebo (double distilled water colored to match the Povidone-Iodine solution in color and taste) application procedure is identical to that of the test product. The manufacturer will provide the placebo.

Concomitant Treatment:

No change will be made in orthodontic treatment. Any application of fluorides or other dental treatment will be recorded from the EHR. The participant and/or caregiver will be asked whether the participant is using any OTC fluoride products or had any fluoride applied by their dentist.

Management of agents (Povi-One and placebo) Povi-One and placebo will be delivered to the clinic site by the manufacturer marked with the different treatment codes. Treatment codes will be retained by the manufacturer until after analysis. Fresh products will be supplied every 6 months and stored at room temperature in locked storage in the orthodontics clinic.

Retention

The drop-out rate of patients in the graduate orthodontic clinic once treatment begins is less than 5%

Sample size determination:

The sample size is based on recent data collected on adolescent patients in the UW graduate orthodontic clinic. Assuming a 50% incidence of any new white spot lesions, as identified by intra-oral photographs at 12 months in the placebo sample, and a reduction of 60% in the test sample, the sample size based on a two-sample chi-square test using a 0.05 significance level and 80% power is 39 participants per group (78 total) without accounting for attrition. Assuming 5% attrition at 12 months, the sample size required is 41 per group (82 total). Assuming an 80% acceptance rate and about 125 new patients in the required age range per year at the UW graduate orthodontic clinic, the sample of 80 patients can be accrued in one 1 year.

Data Management:

The demographic data, clinical evaluation data, and post-treatment reports will be recorded on paper forms precoded with the participant ID. These forms will be collected and kept in a locked file until entered into a computer database. The photographic images will be identified by participant ID and date and uploaded to a secure study computer.

Analysis

The analysis will be based on the intention-to-treat principle. Binary outcomes will be summarized for each study arm and time point by frequency and percentage and quantitative outcomes will be summarized by mean, standard deviation, median, interquartile range, and range. A chi-square test will be used to compare the percentage of patients in each group that develop at least one new white spot lesion. A chi-square will be also used to compare the incidence of any ICDAS score greater than 0 and a two-sample test will be used to compare the mean modified Gingival Index and Acceptability. If the distribution of the modified Gingival Index or Acceptability is skewed, a non-parametric Mann-Whitney U test will be used. Log-linear regression with robust standard errors will used to compare the number of new ICDAS scores greater than 0 if sufficient numbers of participants have more than 1 new lesion (Hardin et al., 2003). If the attrition is greater than 10% at 12 months, multiple imputation methods will be used to account for the missing data and maintain the intention-to-treat analysis (Rubin et al., 1987). All analysis will be performed using R Version 4.3.0 (R Core Team, 2023).