# Phase III RCT of the Effectiveness of Silver Diamine Fluoride in Arresting Cavitated Caries Lesions

> **NIH NIH UH3** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $1,231,593

## Abstract

Summary
The proposed Cooperative Agreement is for support for a Phase III randomized clinical trial (RCT) to assess the
effectiveness of 38% silver diamine fluoride (SDF). SDF recently became available in the U.S., and is non-invasive,
inexpensive and simple to use for management of cavitated lesions exposing dentin clinically (i.e., holes) in primary teeth.
Early childhood caries (ECC) continues to be one of the most prevalent chronic conditions among U.S. children. It also is
one of the most common unmet healthcare needs of poor children (e.g., Head Start children). If allowed to progress
untreated for long periods of time, the disease can have broad dental, medical, social, and quality of life consequences.
ECC and severe-ECC (e.g., multiple cavitated lesions or at least one caries lesion in the anterior teeth, with onset at an
early age) is relatively inexpensive to prevent, yet becomes extremely burdensome on the children and families, and
expensive to treat once lesions cavitate (e.g., with stainless steel crowns, extractions, etc.). This is especially true in young
children who need extensive treatment, or are uncooperative and/or have immature cognitive functioning, disabilities, or
medical conditions, where treatment under general anesthesia, in most cases in hospital operating rooms, is the standard of
care. In 2016, the FDA issued a notice to health care providers that general anesthesia in young children can result in
permanent neurological damage and should be avoided. Thus, better strategies are needed to successfully manage
cavitated caries lesions in young children. The proposed RCT will be accomplished by targeting young children enrolled
in Head Start programs who have cavitated caries lesions that have exposed dentin clinically. Because of the
Breakthrough Therapy Status for SDF, FDA has been heavily involved in the design of this trial to ensure it will meet the
requirements for a cavitated caries lesion “arrest” drug claim, which is innovative in the U.S. The proposed protocol in
this application has been submitted by Advantage Silver Dental Arrest, LLC, holder of IND 124808, to the FDA as part of
our collaboration. In the first months of funding, we will work with NIDCR to review all relevant study documents and
manuals for the RCT, submit to IRBs, and calibrate all study examiners. Following this study preparation period, an
experienced research team will conduct a Phase III, multicenter, randomized, placebo-controlled superiority trial, with
two parallel groups involving a total of 1,040 children, 2-5 years old, who will be followed over a period of 8 months, to
assess: The tooth-Aim 1 (Primary study aim)- the impact of 38% SDF applied twice, 6 months apart, on arrest of cavitated
lesions in the primary dentition (assessed using the ICDAS II severity and activity criteria). Secondary aims will further
assess whether the provision of SDF impacts: the child-Aim 2 [effects of SDF on children's pain and pulpal infection],
and ...

## Key facts

- **NIH application ID:** 9999343
- **Project number:** 5UH3DE027372-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Margherita R Fontana
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,231,593
- **Award type:** 5
- **Project period:** 2017-09-12 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999343

## Citation

> US National Institutes of Health, RePORTER application 9999343, Phase III RCT of the Effectiveness of Silver Diamine Fluoride in Arresting Cavitated Caries Lesions (5UH3DE027372-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999343. Licensed CC0.

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