Povidone Iodine + Fluoride Varnish for Early Childhood Caries

(PIES Trial)

Overseen By Dorota T Kopycka-Kedzierawski, DDS, MPH

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Disqualifiers: Iodine allergy, Thyroid disease, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 24 months

246 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of povidone iodine (an antiseptic) and fluoride varnish can prevent new cavities in young children with severe early childhood caries, a serious form of tooth decay. The study compares this treatment to usual care, which uses a placebo with fluoride varnish. Eligible children have been diagnosed with severe early childhood caries and require dental treatment in an operating room. Participants will receive treatments at multiple points over approximately two years to assess the effectiveness of the new combination in preventing cavities. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important advancements in dental health.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications. However, if you are receiving or have received another investigational drug within 30 days of the baseline visit, you may not be eligible to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that 10% povidone iodine is generally safe for children. Studies have found it can reduce bacteria levels in the mouth, helping to prevent cavities. In one study, none of the children who used povidone iodine developed new cavities, while some who didn't use it did. This suggests the treatment is well-tolerated and benefits dental health. Although the study did not focus on side effects, the safety of povidone iodine in similar situations supports its use. Ongoing trials are expected to provide more detailed safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for early childhood caries involve fluoride applications to strengthen tooth enamel and prevent decay. However, this study treatment is unique because it combines 10% povidone iodine with fluoride varnish. Povidone iodine is an antiseptic that targets and reduces harmful bacteria in the mouth, which can help prevent cavities more effectively than fluoride alone. Researchers are excited about this treatment because it could offer a dual-action approach, enhancing both cavity prevention and bacterial control, which might lead to better oral health outcomes for young children.

What evidence suggests that this treatment might be an effective treatment for early childhood caries?

Research has shown that using 10% povidone iodine (PVPI) can help reduce cavities in children. Studies have found that applying PVPI controls cavities by lowering the amount of harmful bacteria, like Streptococcus mutans, which cause tooth decay. In this trial, one group of participants will receive PVPI combined with fluoride varnish. In one study, none of the children who received PVPI developed new cavities, while five out of 16 children who did not receive it did. This suggests that PVPI could be a promising way to prevent new cavities in children with severe early childhood caries (S-ECC). The treatment also shifts the balance of bacteria in the mouth to less harmful types, offering further protection against tooth decay. ^{1 2 4 5 6}

Who Is on the Research Team?

Dorota T Kopycka-Kedzierawski, DDS, MPH

Principal Investigator

University of Rochester

Are You a Good Fit for This Trial?

This trial is for children aged 24 to 71 months with severe early childhood caries needing treatment in the operating room. It's open to kids in good health and ASA I or II categories. Parents must consent, follow study procedures, and adhere to COVID-19 guidelines. Kids with iodine or seafood allergies, sensitivity to certain food colorings or tea, recent investigational drug use, or thyroid disease can't participate.

Inclusion Criteria

Provide signed and dated informed consent/permission form

My child has severe early tooth decay needing treatment in an OR, as defined by the AAPD.

I am between 2 and almost 6 years old, or I am the adult caregiver of someone in that age range.

Exclusion Criteria

You have allergies to iodine, seafood, red or yellow food coloring, or tea. You also have a history of thyroid disease or are hypersensitive to fluoride varnish.

You cannot have taken any other experimental drugs within the month leading up to the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 10% PVPI or placebo applied to their teeth, followed by fluoride varnish, at baseline and at 3, 6, 9, 12, 15, 18, and 21 months

24 months

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of caries lesions and oral microbiota

24 months

What Are the Treatments Tested in This Trial?

Interventions

• 10% Povidone Iodine

Trial Overview The trial tests if applying a topical solution of 10% povidone iodine plus fluoride varnish (PVPI + FV) prevents new cavities better than placebo plus fluoride varnish (Placebo + FV). Children will be randomly assigned treatments and followed for about two years with applications at several intervals post-baseline.

How Is the Trial Designed?

Group I: Povidone Iodine Experimental Treatment 1 Intervention

10% povidone iodine + fluoride varnish

Group II: Placebo Placebo Group 1 Intervention

Placebo (iced tea) + fluoride varnish

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

Approved in United States as Betadine for:

• Wound care
• Skin disinfection
• Oral care
• Preoperative skin preparation

Approved in European Union as Povidone-Iodine for:

• Wound care
• Skin disinfection
• Oral care
• Preoperative skin preparation
• Periodontal pocket disinfection

Approved in Canada as Povidone-Iodine for:

• Wound care
• Skin disinfection
• Oral care
• Preoperative skin preparation

Approved in Japan as Povidone-Iodine for:

• Wound care
• Skin disinfection
• Oral care
• Preoperative skin preparation

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Published Research Related to This Trial

Short exposure to povidone-iodine (PVP-I) at concentrations of 1:10 and higher significantly decreased osteoblast viability and differentiation, but lower dilutions (1:1000) allowed for recovery in cell proliferation.

The presence of bone-morphogenetic protein-2 (BMP-2) helped restore alkaline phosphatase activity to near control levels, and even undiluted PVP-I showed increased mineral deposition, indicating potential for enhanced bone formation despite initial toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of short-time povidone-iodine application on osteoblast proliferation and differentiation. Schmidlin, PR., Imfeld, T., Sahrmann, P., et al.[2021]

The combination of 10% povidone iodine (PVP-I) and 5% sodium fluoride (NaF) in a dental varnish was well tolerated by 16 healthy adult participants, with no adverse events reported, indicating its safety for use.

After application, serum levels of iodine and fluoride increased temporarily but remained within normal ranges after 24 hours, suggesting effective but controlled absorption of the active ingredients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Iodine and Fluoride following Application of an Anticaries Varnish in Adults. Lin, YS., Rothen, ML., Milgrom, P.[2020]

A 9-year-old boy with suspected PVP-I allergy experienced anaphylaxis after using a PVP-I solution, but skin prick tests were negative, highlighting the challenge in diagnosing PVP allergies.

The histamine release test (HRT) proved useful in confirming the allergy, as it showed histamine release when basophils were exposed to PVP in the presence of serum, suggesting that negative skin tests do not completely rule out PVP allergy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anaphylaxis to polyvinylpyrrolidone in povidone-iodine for impetigo contagiosum in a boy with atopic dermatitis. Yoshida, K., Sakurai, Y., Kawahara, S., et al.[2017]

A case report of a 13-year-old patient revealed that daily disinfection of fasciotomy wounds with povidone-iodine (PVP-I) may have led to iodide absorption, contributing to hypothyroidism and prolonged kidney injury after severe abdominal sepsis.

After stopping PVP-I exposure and starting thyroid hormone treatment, the patient's kidney function improved, suggesting that PVP-I toxicity and/or hypothyroidism could have played a role in the persistent renal failure, highlighting the need for careful monitoring of PVP-I use in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Povidone Iodine Disinfection Associated with Hypothyroidism and Potentially Contributing to Prolonged Kidney Failure. Vercammen, Y., Dauwe, D., De Vlieger, G., et al.[2022]

Liposomal formulations of povidone-iodine (PVP-I) are significantly less toxic to blood vessels compared to traditional aqueous PVP-I formulations, as demonstrated in a study using chick embryo models.

The study showed that liposomal PVP-I formulations reduced angiotoxic effects, such as coagulation and hemorrhages, indicating a safer option for local anti-infective treatments, especially in wound care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative testing of liposomal and aqueous formulations of povidone-iodine for their angioirritative potential at the chorioallantoic membrane of ex ovo cultivated chick embryos. Wutzler, P., Sauerbrei, A., Härtl, A., et al.[2017]

In a study involving 16 adults with periodontitis, subgingival irrigation with 10% PVP-iodine combined with scaling and root planing led to a significant 95% reduction in total pathogen counts in 44% of deep periodontal pockets, compared to only 6-13% reduction with other treatments.

The addition of PVP-iodine irrigation to mechanical therapy also resulted in a greater reduction in probing pocket depth (1.8 mm) compared to PVP-iodine alone (0.9 mm) or saline (0.9 mm), suggesting that PVP-iodine is most effective when used alongside traditional periodontal treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Povidone-iodine as a periodontal pocket disinfectant. Hoang, T., Jorgensen, MG., Keim, RG., et al.[2019]

A 5% povidone-iodine cream (PVP-I) demonstrated rapid antimicrobial activity, effectively killing a range of bacteria within 60 seconds, compared to over 15 minutes for a combination-antibiotic cream (Neosporin).

In clinical trials involving standardized wounds infected with Staphylococcus aureus, PVP-I cream showed significant reductions in bacterial counts and faster healing compared to no treatment, with minimal irritation reported during application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The comparative efficacy and safety of 5% povidone-iodine cream for topical antisepsis. Stahl-Bayliss, CM., Grandy, RP., Fitzmartin, RD., et al.[2017]

Povidone iodine (PVP-I) is widely used as a pre-operative antiseptic, but there are rare cases of allergic reactions, as demonstrated in two patients who developed allergic contact dermatitis after its use.

While PVP-I is generally considered a low sensitizer, this case highlights the need for further evaluation of its potential to cause allergic reactions, suggesting that pre-operative allergy testing for PVP-I may be worth considering in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unusual complication of late onset allergic contact dermatitis to povidone iodine in oral & maxillofacial surgery - a report of 2 cases. Reyazulla, MA., Gopinath, AL., Vaibhav, N., et al.[2017]

Citations

1. oss.jocpd.com oss.jocpd.com/files/article/20220808-954/pdf/JOCPD.34.3.233.pdf

Efficacy of 10% Povidone Iodine in Children Affected with ... Results revealed that application of 10% Povidone Iodine ... Effect of. Povidone- iodine on Streptococcus Mutans in children with Extensive. Dental Caries.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05272254

NCT05272254 | Povidone Iodine Efficacy Study To assess the efficacy of 10% PVPI in children with S-ECC to prevent new cavitated caries lesions that require follow-up restorative/surgical intervention ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20578661/

Efficacy of 10% Povidone Iodine in children affected with ... 10% Povidone Iodine application can be a good alternative to control dental caries in children affected with Early Childhood Caries (ECC).

4. aapd.org aapd.org/globalassets/media/publications/archives/amin-26-01.pdf

Effect of Povidone-iodine on Streptococcus Mutansin ... 15 While none of the children in the PVP-I group developed caries, 5 of the 16 in the placebo group had caries in 8 months. Long-term follow-up corroborated the ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2452231720300087

Adjunctive dental therapies in caries-active children We have determined that treatment with povidone iodine can shift the composition of the salivary cariogenic microbiome to include higher proportions of aerobic ...

6. jocpd.com jocpd.com/articles/10.17796/jcpd.34.3.l552816527xtv122

Efficacy of 10% Povidone Iodine in Children Affected with ... Results revealed that application of 10% Povidone Iodine caused a significant reduction in the rise of Streptococcus mutans levels from the baseline ...