Cavities of TeethPhase 3NCT03649659
Effectiveness of Silver Diamine Fluoride (SDF) in Arresting Cavitated Caries Lesions
A Phase 3 study testing Silver Diamine Fluoride in people with Cavities of Teeth, run by University of Michigan at 3 sites in United States.
Trial summary
This trial is a Phase III, multisite, randomized, placebo-controlled trial, with two parallel groups. The groups are SDF or placebo and they are applied every 6 months. The primary hypothesis of the trial is that SDF is better than placebo for stopping cavities with dentin exposed in baby teeth when assessed at 6… Read more about this study
- Who is it for?
- Ages 12 to 71 months
- Conditions the study is for
- Cavities of Teeth
- What is being tested?
- Silver Diamine Fluoride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 830 participants
- Where
- 3 sitesUnited States
- Study dates
- 8 Oct 2018to 27 Apr 2023
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 71 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Child:
- Male or female, between 12-71 months of age at baseline, up to the day the child turns 6 years old.
- Must allow examination of the oral cavity and application of treatment by the examiners at baseline.
- Must have S-ECC [defined as: In children younger than age 3, any sign (non-cavitated or cavitated lesion) of caries in any tooth surface (i.e., most common for this age group will be on erupted smooth surfaces). From ages 3 through 5, ≥1 dmfs in maxillary anterior teeth; or a dmfs score of ≥4 (age 3), ≥5 (age 4), or ≥6 (age 5) constitutes S-ECC. Note: The "d" component of the dmfs index is defined as including cavitated and non-cavitated lesions, thus ICDAS>1].
- Have at least one SDF-target tooth with
- Soft cavitated caries lesions extending into dentin [ICDAS 5 or 6];
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- Cavitated lesion(s) that allow for direct hardness assessment and application of SDF (microbrush applicator must fit the cavity and be able to access all exposed dentin).
- Parent/Legal Guardian:
- Provide written informed consent for the child and her/himself prior to participation.
- Must be at least 18 years old, or an emancipated minor who provides documentation of emancipation.
- Must be willing and able to participate in trial activities.
Who cannot join
- Child:
- Hereditary generalized developmental dental defects such as Amelogenesis Imperfecta and Dentinogenesis Imperfecta.
- Known allergy/sensitivity to silver or other heavy metal ions.
- Presence of any gingival or peri-oral ulceration, abscess or stomatitis.
- Participating in the foster care system at trial initiation.
- Toothache pain at baseline (based on Dental Discomfort Questionnaire score of 1 or higher).
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- Note: If toothache pain occurs after baseline, the child remains eligible to continue in the trial as long as he/she has at least one trial tooth that meets tooth inclusion/exclusion criteria.
- Demonstrated inability to comply with trial protocol requirements (determination is at the Clinical Site Investigator's discretion).
- Rickets.
- Osteopenia or osteoporosis (e.g., Osteogenesis Imperfecta, Ehlers-Danlos Syndrome, Marfan Syndrome, etc.).
- Chronic diseases such as chronic kidney disease, leukemia, lymphoma, rheumatic disorders, etc.
- Metabolic bone disease (e.g., Galactosemia, Glycogen Storage Disease Type 1, etc.).
- Chronic glucocorticoid, anticonvulsants, chemotherapy, bisphosphonate administration.
- Hypothyroidism, hyperparathyroidism, impaired glucose tolerance, hypocalcemia or hypophosphatemia.
- Tooth:
- Pain due to caries (based on DDQ score of 1 or higher).
- Note: If toothache pain occurs after baseline, the tooth is removed from the study.
- Pulpal exposure, or signs of pulpal infection (abscess, fistula, swelling).
- Mobility not associated with expected exfoliation patterns.
- Parent/Legal Guardian:
- Demonstrated inability to comply with trial protocol requirements (determination is at the Clinical Site Investigator's discretion).
- Inability to read and comprehend the consent document or trial questionnaires in the translated languages available.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Michigan School of Dentistry
Ann Arbor, Michigan, 48109
University of Iowa College of Dentistry
Iowa City, Iowa, 52242
New York University College of Dentistry
New York, New York, 10010
About this study
Official title: Phase III RCT of the Effectiveness of Silver Diamine Fluoride in Arresting Cavitated Caries Lesions
This trial is a Phase III, multisite, randomized, placebo-controlled trial, with two parallel groups. The groups are SDF or placebo and they are applied every 6 months. The primary hypothesis of the trial is that SDF is better than placebo for stopping cavities with dentin exposed in baby teeth when assessed at 6 months after initial application.
Read the detailed description
This trial is a phase III, multicenter, randomized, placebo-controlled superiority trial, with two parallel groups (placebo vs. SDF applied to cavitated lesions) involving a total of 1144 children with the primary outcome assessed at 6 months after initial treatment.
One thousand one hundred forty four children, 12-71 months of age, from early childhood education programs, such as Head Start centers, Early Head Start centers, and equivalent city/state subsidized preschool programs, or children attending dental clinics associated with the clinical trial sites, will be randomized, in two cohorts. Trial visits will occur at baseline, 3 months, 6 months, and 8 months. SDF/placebo will be applied at baseline and 6 months. Parents/legal guardians will be called 24 to 48 hours after the SDF/placebo application to assess adverse events and unanticipated problems and in-person visits for safety exams will be available for all child participants approximately 24 to 48 hours after SDF/placebo application. This visit could happen before or after the 24- to 48-hour call with the parent or legal guardian, but every attempt will be made so that the call occurs prior to the 24- to 48-hour visit. Additionally, intermediate contacts at 1.5 months, 4.5 months, and 7 months will occur to determine if the child needs an additional visit to assess pain, lesion progression, etc. and to maintain contact with the participant.
Randomization to SDF application (treatment) or placebo (control) will be at the participant-level; all teeth within a participant that meet the inclusion criteria will receive the same trial product. Both treatment and control will be dispensed from identical unit-dose ampules coded and labeled to ensure masking of all trial personnel. The number of ampules required to treat all carious lesions in the participant's mouth will be recorded. No caries removal will be performed. Teeth will be cleaned with a toothbrush and will be dried with cotton/gauze, and the solution will be painted on the dentin of each targeted cavitated lesion using a standardized applicator. Following application, the tooth will be blotted dry with gauze.
At each clinical visit International Caries Detection and Assessment System (ICDAS) examinations, including cavitated lesion hardness assessments, soft tissue assessments and questionnaires on dental discomfort, family impact and treatment satisfaction and acceptability will be collected.
- Conditions
- Cavities of Teeth
- Being tested
- Silver Diamine Fluoride, Placebo
- Medical subject headings
- Dental Caries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Silver Diamine FluorideDrug
Also called Diammine Silver Fluoride
SDF will be applied twice during the study
PlaceboDrug
This is being compared to the SDF and will also be applied twice
| Study group | Role | What they receive |
|---|---|---|
| Silver Diamine Fluoride (SDF) | Experimental | SDF will be applied to the affected teeth twice during the study. Once at screening/baseline and again at the 6-month visit. Receives: Drug: Silver Diamine Fluoride |
| Placebo | Placebo comparator | The placebo will be applied to the affected teeth twice during the study. Once at screening/baseline and again at the 6-month visit. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Proportion of Arrested Trial Lesions Per Child in Each Treatment Arm After One Treatment With SDF or Placebo
Arrested trial lesions will be assessed by determining if the lesion is hard or soft by pressing on the lesion using a standard probe as assessed by calibrated examiners.
Measured: 6 months
Secondary outcomes (3)
The Proportion of Arrested Trial Lesions Per Child in Each Treatment Arm After Two Treatments With SDF or Placebo
Arrested trial lesions will be assessed by determining if the lesion is hard or soft after two SDF applications by pressing on the lesion using a standard probe as assessed by calibrated examiners.
Measured: 8 months
Proportion of Arrested Trial Lesions Per Child in Each Treatment Arm After One Treatment With SDF or Placebo
Proportion of arrested trial lesions will be assessed by determining if the lesion is hard or soft by pressing on the lesion using a standard probe as assessed by calibrated examiners. The effect of a single application will be assessed at 3-month follow-up post initial treatment.
Measured: 3 months
Proportion of Trial Lesions With Pain Prior to or at the 8-month Visit
The presence of pain associated with a trial lesion was screened at baseline a score of 1 or higher using the Dental Discomfort Questionnaire (DDQ). The DDQ is a validated tool assessing pain in children 5 and younger, as reported by parents/legal guardians, based on observation of toothache pain-related behaviors by the child. It consists of two parts: a question of the occurrence of toothache and when (if no pain DDQ score of 0,best), and 8 validated questions about behaviors associated with toothache or discomfort due to caries on a three-point scale: 0 'never', 1 'sometimes', and 2 'often'. Total score is the sum of the 8 questions in part two, ranging from 0 (no pain) to 16 (worst score). A DDQ score of 1 or higher may not be caused by pain in a trial tooth, so children with a DDQ score of 1 or higher were examined during a clinical visit to determine if the trial teeth had pain. Pain associated with a trial tooth at any time after baseline treatment counted as trial lesion pain.
Measured: Baseline, 24-48 hour call, 1.5 month, 3 month, 4.5 month, 6 month, 24-48 hours after 6 month, 7 month, 8 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2018
- Study start8 Oct 2018
- Primary completion11 Apr 2023
- Study completion27 Apr 2023
Why it stopped: The trial stopped early due to meeting interim analysis early stopping rules. Active participants at the time of the interim analyses results did complete their remaining study visits. No new participants were enrolled.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cavities of TeethStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 830 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- NYU Langone Health, University of Iowa, National Institute of Dental and Craniofacial Research (NIDCR)
- Responsible party
- Principal investigator, Margherita Fontana, University of Michigan
- Investigators
- Margherita Fontana, DDS, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03649659
- Sponsor's protocol ID
- HUM00147622
- Other IDs
- U01DE027372
- Status last verified
- Aug 2026
- First submitted
- 24 Aug 2018
- Last updated
- 12 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fontana M, Moursi A, Gonzalez-Cabezas C, Khera D, Levy SM, Eckert GJ, Katz BP, Tenuta LMA, Campos MS, Karl E, Boynton J, Chinn C, Sheen A, Kolker J, Warren J, Thorpe E. Efficacy of Silver Diamine Fluoride on Young Children With Severe Early Childhood Caries: A Randomized Clinical Trial. JAMA Pediatr. 2026 Jul 27:e262567. doi: 10.1001/jamapediatrics.2026.2567. Online ahead of print.
PubMed 42507437