Povidone-Iodine for Preventing White Spots

Overseen By Sanghee Lee, DDS, MSc, MS

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: Antibiotics

Disqualifiers: Iodine allergy, Thyroid disease, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 9 months

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a thyroid disease or are using antibiotics regularly, you may not be eligible to participate.

What data supports the effectiveness of the treatment Povidone-Iodine for preventing white spots?

Research shows that povidone-iodine, a key ingredient in the treatment, is effective in reducing infections in various medical settings, such as preventing infections in sutured wounds and during eye surgeries. This suggests it may help prevent white spots by reducing bacterial presence. ^{1 2 3 4 5}

Is Povidone-Iodine safe for use in humans?

Povidone-Iodine is generally considered safe as a widely used antiseptic, but it can cause skin irritation or burns if used improperly, especially with prolonged exposure. It may also be absorbed into the body, potentially affecting thyroid function, so it should be used carefully. ^{1 6 7 8 9}

How is the drug Povidone-Iodine unique in preventing white spots?

Povidone-Iodine is unique because it is a broad-spectrum antiseptic that is applied topically, meaning it is used directly on the skin or affected area. It is known for its ability to kill a wide range of bacteria, which may help prevent white spots by reducing bacterial growth. ^{2 4 10 11 12}

What is the purpose of this trial?

The goal of this clinical trial is to learn if topical application on the all surface of 10% Povidone Iodine (Povi-One) in healthy participants in transitional or permanent dentition (10-17 y) prevents new white spot lesions in the maxillary anterior teeth at 1 year of follow-up. Researchers will compare Povi-One to a placebo to see if Povi-One works to prevent new white spot lesions. It will also learn about the safety of topical 10% Povidone Iodine. The main questions it aims to answer are: 1. Does Povi-One prevent the development of any white spot lesion on the surface of maxillary anterior teeth? 2. Does Povi-One lower the probability of any International Caries Detection and Assessment System (ICDAS) score greater than 0 and mean modified Löe-Silness Gingival Index (GI) in the intervention group? Researchers will 1. Score GI without cleaning participants teeth, then score ICDAS of maxillary and mandibular incisors after participants brush and floss their teeth and take a photograph of maxillary 6 anterior teeth 2. Apply Povi-one (or control) at the consultation appointment before placing fixed orthodontic appliances and 3, 6, and 9 months after appliance placement Researchers will 1. Recall using Zoom 24-48 hours after the first application of Povi-One and examine the participant's mouth for oral lesions using a structured paper checklist 2. Interview the caregiver to complete a paper questionnaire on adverse effects Researchers will 1. Score GI, and then score ICDAS of maxillary and mandibular incisors in 6, 12 months after appliance placement 2. Evaluate the development of white spot lesions on maxillary central and lateral incisors in 6, and 12 months after appliance placement

Research Team

Greg Huang, DMD, MSD, MPH

Principal Investigator

University of Washington

Eligibility Criteria

This trial is for healthy individuals aged 10-17 with transitional or permanent teeth, who are getting fixed orthodontic appliances. They should not have any existing white spot lesions on their maxillary anterior teeth.

Inclusion Criteria

I have at least 4 permanent front teeth in both my upper and lower jaws.

My braces are expected to be on for at least a year.

I am a healthy child or teenager aged between 10 and 17.

Exclusion Criteria

Allergies to iodine

I have been diagnosed with a thyroid condition.

Conditions that could impair routine oral hygiene procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline and Initial Treatment

Povi-One or placebo is applied topically to all tooth surfaces at the consultation appointment before the placement of fixed appliances

1 week

1 visit (in-person)

Treatment

Povi-One or placebo is applied at 3, 6, and 9 months after appliance placement. Participants are monitored for oral lesions and adverse effects.

9 months

3 visits (in-person), 1 visit (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of white spot lesions and gingival index

3 months

2 visits (in-person)

Treatment Details

Interventions

• Topical 10% Povidone-Iodine

Trial Overview The study tests if a topical solution called Povi-One (10% Povidone-Iodine) can prevent new white spot lesions on the front upper teeth over one year compared to a placebo. It involves applying the solution at specific times and monitoring through dental exams.

Participant Groups

Group I: Povidone-iodine solution Experimental Treatment 1 Intervention

10% Povidone and Iodine will be applied

Group II: Placebo Placebo Group 1 Intervention

Placebo (double distilled water matched in color and taste) will be applied

Topical 10% Povidone-Iodine is already approved in United States, European Union for the following indications:

Approved in United States as Povi-One for:

• Prevention of white spot lesions
• Caries prevention

Approved in European Union as Betadine for:

• Prevention of white spot lesions
• Caries prevention
• Oral antiseptic

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Findings from Research

The application of 5% povidone iodine (Betadine) to the eye significantly reduced visual acuity and contrast sensitivity in a study of 10 subjects, indicating potential negative effects on visual function.

Betadine also increased subjective complaints of discomfort and corneal staining, suggesting that while it may be effective for disinfection, it can compromise corneal integrity and overall eye comfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Povidone Iodine 5% on the Cornea, Vision, and Subjective Comfort. Ridder, WH., Oquindo, C., Dhamdhere, K., et al.[2018]

In a study involving 105 patients undergoing cataract surgery, 5% povidone-iodine (PI) was found to be significantly more effective than 1% PI in reducing bacterial colonies on the conjunctiva, especially when initial bacterial loads were high.

While in vitro studies suggested that lower concentrations of PI might be more effective, this in vivo study demonstrated that 5% PI resulted in a greater reduction in bacterial counts, indicating its superior efficacy as a preoperative antiseptic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of 5% povidone-iodine solution against 1% povidone-iodine solution in preoperative cataract surgery antisepsis: a prospective randomised double blind study. Ferguson, AW., Scott, JA., McGavigan, J., et al.[2019]

In a randomized controlled pilot study of adult patients with superficial skin abscesses, the addition of povidone-iodine (PVP-I) to standard incision and drainage (I&D) treatment did not significantly improve clinical cure rates, with 88.2% in the PVP-I group compared to 91.3% in the standard care group.

However, the PVP-I group experienced a significantly higher rate of adverse events (59.6%) compared to the standard care group (26.5%), primarily due to local skin irritation, indicating that while PVP-I may not enhance efficacy, it may increase the risk of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study to Evaluate the Adjunct Use of a Povidone-Iodine Topical Antiseptic in Patients with Soft Tissue Abscesses. Olson, AS., Rosenblatt, L., Salerno, N., et al.[2019]

In a study involving 150 patients undergoing cataract surgery, a new 5% povidone iodine preparation was found to be safe for the eye, with no harmful effects observed during a 60-day follow-up.

Microbiological tests on 60 patients showed a significant reduction in bacterial colonies in the eye after using the povidone iodine, indicating its effectiveness as an antiseptic before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Iodized polyvidone (betadine) and prevention of postoperative infection. A multicenter study]. Lagoutte, F., Fosse, T., Jasinski, M., et al.[2017]

In a study of 500 emergency department patients with traumatic lacerations, using a topical 1% povidone-iodine solution before suturing significantly reduced the infection rate compared to wounds treated with normal saline alone.

Only 5.4% of wounds treated with povidone-iodine became infected, compared to 15.46% of control wounds, indicating that povidone-iodine is an effective antiseptic for preventing infections in traumatic lacerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial of povidone-iodine in the prevention of infection in sutured lacerations. Gravett, A., Sterner, S., Clinton, JE., et al.[2019]

A study on Göttingen Minipigs® showed that daily application of 7.5% and 10% povidone-iodine (PVP-I) for up to 39 weeks was safe, with no skin irritation or thyroid dysfunction observed.

Despite increased serum iodine levels, the treatment did not lead to endocrine disruption, suggesting that PVP-I could provide antimicrobial benefits in humans without significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of dermal toxicity and toxicokinetics of povidone‑iodine in Göttingen minipigs. Eddy, EP., Shet, MS., Cataldo, M., et al.[2023]

A case study of a one-year-old boy revealed that prolonged exposure to 10% povidone-iodine (PVP-I) for 4 hours led to a chemical burn, highlighting the potential risks of extended use of this antiseptic.

Patch testing indicated that while PVP-I is generally safe, prolonged wet exposure can cause skin irritation or contact dermatitis, as shown by positive reactions in 16 out of 17 volunteers when tested with a wet chamber.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemical burn caused by povidone-iodine]. Nakano, S., Uchiyama, A., Ueyama, H., et al.[2017]

Povidone-iodine, while generally considered a low irritant antiseptic, can cause severe contact dermatitis when used improperly, particularly in areas where it pools or is occluded during surgery, as observed in 27 patients evaluated between 2011 and 2013.

The dermatitis typically appeared the day after surgery, and patch testing showed no allergic reaction to povidone-iodine, suggesting that the irritation was due to prolonged skin contact rather than an allergic response, highlighting the need for better drying practices to prevent this complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Povidone-iodine induced post-surgical irritant contact dermatitis localized outside of the surgical incision area. Report of 27 cases and a literature review. Borrego, L., Hernández, N., Hernández, Z., et al.[2017]

A survey of 28 pediatric surgical units in the UK revealed that most units prefer using Betadine for skin preparation in premature neonates, despite its use being outside the product license.

Evidence suggests that chlorhexidine is more effective than povidone iodine for preoperative skin antisepsis, but both can cause skin damage, and povidone iodine may lead to reactive hypothyroidism in neonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Antiseptic Use in Pediatric Surgical Units in the United Kingdom-Where Is the Evidence Base? Ng, AL., Jackson, C., Kazmierski, M.[2017]

The study found that while 10% Betadine solution effectively inhibited the growth of Staphylococcus aureus, it did not completely kill other tested bacteria, including Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter baumannii.

The research highlighted that using only the zone of inhibition assay is insufficient for assessing antimicrobial effectiveness; a colony-forming unit assay is necessary for a more accurate evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An in vitro Study of Betadine's Ability to Eliminate Live Bacteria on the Eye: Should It Be Used for Protection against Endophthalmitis? Nagle, A., Kopel, J., Reed, J., et al.[2022]

Diluted povidone-iodine remains stable for up to 28 days and demonstrates strong antibacterial efficacy against common ocular pathogens like Staphylococcus aureus and Pseudomonas aeruginosa, with effective concentrations as low as 0.078% and 0.3%, respectively.

While povidone-iodine is effective, it can cause mild ocular irritation, especially at higher concentrations, indicating a need for careful concentration management in ophthalmic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex vivo evaluation of the stability, safety and antibacterial efficacy of an extemporaneous povidone-iodine preparation for ophthalmic applications. Lee, S., Khun, D., Kumarasinghe, GL., et al.[2020]

Povidone-iodine solution (Betadine) is recognized as an effective antiseptic and disinfectant in colorectal surgeries, aimed at reducing postoperative infections and cancer recurrence.

Despite its widespread use, there is a lack of sufficient randomized controlled trials to fully establish the optimal application methods and potential side effects of povidone-iodine in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits of povidone-iodine solution in colorectal operations: science or legend. Pattana-arun, J., Wolff, BG.[2017]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effect of Povidone Iodine 5% on the Cornea, Vision, and Subjective Comfort. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Comparison of 5% povidone-iodine solution against 1% povidone-iodine solution in preoperative cataract surgery antisepsis: a prospective randomised double blind study. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Pilot Study to Evaluate the Adjunct Use of a Povidone-Iodine Topical Antiseptic in Patients with Soft Tissue Abscesses. [2019]

4. France pubmed.ncbi.nlm.nih.gov

[Iodized polyvidone (betadine) and prevention of postoperative infection. A multicenter study]. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

A trial of povidone-iodine in the prevention of infection in sutured lacerations. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Evaluation of dermal toxicity and toxicokinetics of povidone‑iodine in Göttingen minipigs. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

[Chemical burn caused by povidone-iodine]. [2017]

8. England pubmed.ncbi.nlm.nih.gov

Povidone-iodine induced post-surgical irritant contact dermatitis localized outside of the surgical incision area. Report of 27 cases and a literature review. [2017]

9. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Antiseptic Use in Pediatric Surgical Units in the United Kingdom-Where Is the Evidence Base? [2017]

10. Switzerland pubmed.ncbi.nlm.nih.gov

An in vitro Study of Betadine's Ability to Eliminate Live Bacteria on the Eye: Should It Be Used for Protection against Endophthalmitis? [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Ex vivo evaluation of the stability, safety and antibacterial efficacy of an extemporaneous povidone-iodine preparation for ophthalmic applications. [2020]

12. United States pubmed.ncbi.nlm.nih.gov

Benefits of povidone-iodine solution in colorectal operations: science or legend. [2017]