Cavities of Teeth
Conditions
Brief 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 months after initial application.
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.
Interventions
DRUGSilver Diamine Fluoride
SDF will be applied twice during the study
DRUGPlacebo
This is being compared to the SDF and will also be applied twice
Sponsors
University of Michigan
NYU Langone Health
University of Iowa
National Institute of Dental and Craniofacial Research (NIDCR)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Months to 71 Months
Healthy volunteers
No
Inclusion criteria
* 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 \[ICDAS 5 or 6\]; * 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.
Exclusion criteria
* 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). * 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Arrested Trial Lesions Per Child in Each Treatment Arm After One Treatment With SDF or Placebo | 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Arrested Trial Lesions Per Child in Each Treatment Arm After Two Treatments With SDF or Placebo | 8 months | 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. |
| Proportion of Arrested Trial Lesions Per Child in Each Treatment Arm After One Treatment With SDF or Placebo | 3 months | 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. |
| Proportion of Trial Lesions With Pain Prior to or at the 8-month Visit | 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 | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMargherita Fontana, DDS, PhD
University of Michigan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Silver Diamine Fluoride (SDF) SDF will be applied to the affected teeth twice during the study. Once at screening/baseline and again at the 6-month visit.
Silver Diamine Fluoride: SDF will be applied twice during the study | 414 |
| Placebo The placebo will be applied to the affected teeth twice during the study. Once at screening/baseline and again at the 6-month visit.
Placebo: This is being compared to the SDF and will also be applied twice | 416 |
| Total | 830 |
Baseline characteristics
| Characteristic | Silver Diamine Fluoride (SDF) | Placebo | Total |
|---|---|---|---|
| Age, Customized Child Age 1 Years | 15 Participants | 19 Participants | 34 Participants |
| Age, Customized Child Age 2 Years | 56 Participants | 56 Participants | 112 Participants |
| Age, Customized Child Age 3 Years | 124 Participants | 107 Participants | 231 Participants |
| Age, Customized Child Age 4 Years | 155 Participants | 170 Participants | 325 Participants |
| Age, Customized Child Age 5 Years | 64 Participants | 64 Participants | 128 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 182 Participants | 183 Participants | 365 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 228 Participants | 219 Participants | 447 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 14 Participants | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 26 Participants | 24 Participants | 50 Participants |
| Race (NIH/OMB) Black or African American | 85 Participants | 86 Participants | 171 Participants |
| Race (NIH/OMB) More than one race | 24 Participants | 37 Participants | 61 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 138 Participants | 134 Participants | 272 Participants |
| Race (NIH/OMB) White | 138 Participants | 132 Participants | 270 Participants |
| Region of Enrollment United States | 414 participants | 416 participants | 830 participants |
| Sex: Female, Male Female | 228 Participants | 200 Participants | 428 Participants |
| Sex: Female, Male Male | 186 Participants | 216 Participants | 402 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 414 | 0 / 416 |
| other Total, other adverse events | 103 / 414 | 89 / 416 |
| serious Total, serious adverse events | 3 / 414 | 1 / 416 |
Outcome results
Primary
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.
Time frame: 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Silver Diamine Fluoride (SDF) | The Proportion of Arrested Trial Lesions Per Child in Each Treatment Arm After One Treatment With SDF or Placebo | 54 percentage of lesions arrested |
| Placebo | The Proportion of Arrested Trial Lesions Per Child in Each Treatment Arm After One Treatment With SDF or Placebo | 22.5 percentage of lesions arrested |
p-value: <0.000199.9% CI: [2.54, 6.48]Regression, Logistic
Secondary
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.
Time frame: 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Silver Diamine Fluoride (SDF) | Proportion of Arrested Trial Lesions Per Child in Each Treatment Arm After One Treatment With SDF or Placebo | 57.5 percentage of lesion arrest |
| Placebo | Proportion of Arrested Trial Lesions Per Child in Each Treatment Arm After One Treatment With SDF or Placebo | 18.8 percentage of lesion arrest |
p-value: <0.000199.9% CI: [3.59, 9.51]Regression, Logistic
Secondary
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.
Time frame: 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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Silver Diamine Fluoride (SDF) | Proportion of Trial Lesions With Pain Prior to or at the 8-month Visit | 2.7 percentage of trial lesions with pain |
| Placebo | Proportion of Trial Lesions With Pain Prior to or at the 8-month Visit | 2.8 percentage of trial lesions with pain |
p-value: 0.894299.9% CI: [0.25, 3.54]Regression, Logistic
Secondary
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.
Time frame: 8 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Silver Diamine Fluoride (SDF) | The Proportion of Arrested Trial Lesions Per Child in Each Treatment Arm After Two Treatments With SDF or Placebo | 50.2 percentage of lesions arrested |
| Placebo | The Proportion of Arrested Trial Lesions Per Child in Each Treatment Arm After Two Treatments With SDF or Placebo | 17.4 percentage of lesions arrested |
p-value: <0.000199.9% CI: [2.84, 8.05]Regression, Logistic