Dental Caries
Conditions
Keywords
Dental Caries, Dental Restorative Materials, Dental Composite, Bisphenol-A
Brief summary
The Composites and Urinary Bisphenol-A Study (CUBS) is a clinical study of dental composite for its effects on urinary bisphenol-A levels. The study will enroll approximately 139 children recruited from study-affiliated clinical sites in New England.The primary aim of CUBS is to test the hypothesis that urinary bisphenol-A (BPA) concentrations increase after composite restoration placement. BPA is a chemical used in the synthesis of matrix monomers and has been shown to have harmful effects in toxicological studies in laboratory animals. Currently it is unknown whether dental composite restorative materials containing monomers that are derived from BPA result in chronic low-dose BPA exposure in children.
Detailed description
Study subjects will be new or existing patients of the clinical sites who are in need of dental restorations, meet all eligibility criteria, and provide informed consent/assent to participate. Subjects will be asked to provide two pre-treatment urine samples and three post-treatment samples. Urine collections occur next-day and 14 days after treatment, with one final urine collected approximately 6 months later (marking the end of the subject's active study participation). Data will be collected from the clinician's standard oral examination (including new and existing dental treatments), the data collector's measurements of height and weight and interviews administered to the parents/guardians to assess sociodemographic and other relevant factors (e.g., recent food/beverage consumption). Confidentiality will be maintained by assigning each subject a unique number and using only this number or aggregate data in all study reports. All study records will be securely maintained with access limited to essential study personnel only.
Interventions
Dental Restoration (bisphenol A diglycidyl ether methacrylate based composite)
Sponsors
National Institute of Environmental Health Sciences (NIEHS)
Harvard School of Public Health (HSPH)
Carelon Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Aged 3-16 (\<17) years at enrollment. * 2+ posterior teeth with caries requiring restorations treatable by composite. * Toilet-trained (not using diapers, pull-ups, or training pants during day or night).
Exclusion criteria
* Medical conditions that would render the subject physically unable to provide urine samples. * Guardian is not proficient in spoken English or Spanish language * Child is aged 8.0 years or older and not proficient in spoken English or Spanish language * Living \>35 miles outside of the dental clinic or the NERI office (Watertown MA)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urinary Bisphenol A Level (BPA) From Baseline to 6 Months | From Baseline to 6 months | BPA was measured, corrected for specific gravity, in ng/mL. We corrected BPA for specific gravity (SG) using the formula: BPA \* \[(meanSG - 1)/(SG - 1)\], where meanSG is the mean of the SG for the samples examined. Urine samples were collected twice pre-treatment and the geometric mean of BPA at each pre-treatment visit was used as the baseline BPA. Change in BPA was computed using BPA at follow-up minus BPA at baseline. Analysis of change in BPA was done using the arithmetic mean. |
| Change in Urinary Bisphenol A Level (BPA) From Baseline to 1 Day After the First Dental Treatment | From Baseline to 1 day after the first dental treatment (The first dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically within a few weeks of baseline.) | BPA was measured, corrected for specific gravity, in ng/mL. We corrected BPA for specific gravity (SG) using the formula: BPA \* \[(meanSG - 1)/(SG - 1)\], where meanSG is the mean of the SG for the samples examined. Urine samples were collected twice pre-treatment and the geometric mean of BPA at each pre-treatment visit was used as the baseline BPA. Change in BPA was computed using BPA at 1 day after the first dental treatment minus BPA at baseline. The first dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically within a few weeks of baseline. Analysis of change in BPA was done using the arithmetic mean. |
| Change in Urinary Bisphenol A Level (BPA) From Baseline to 14 Days After the First Dental Treatment | From Baseline to 14 days after the first dental treatment (The first dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically within a few weeks of baseline.) | BPA was measured, corrected for specific gravity, in ng/mL. We corrected BPA for specific gravity (SG) using the formula: BPA \* \[(meanSG - 1)/(SG - 1)\], where meanSG is the mean of the SG for the samples examined. Urine samples were collected twice pre-treatment and the geometric mean of BPA at each pre-treatment visit was used as the baseline BPA. Change in BPA was computed using BPA at 14 days after the first dental treatment minus BPA at baseline. The first dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically within a few weeks of baseline. Analysis of change in BPA was done using the arithmetic mean. |
| Change in Urinary Bisphenol A Level (BPA) From Baseline to 1 Day After the Second Dental Treatment | From Baseline to 1 day after the second dental treatment (The second dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically 3-4 weeks after the first dental treatment.) | BPA was measured, corrected for specific gravity, in ng/mL. We corrected BPA for specific gravity (SG) using the formula: BPA \* \[(meanSG - 1)/(SG - 1)\], where meanSG is the mean of the SG for the samples examined. Urine samples were collected twice pre-treatment and the geometric mean of BPA at each pre-treatment visit was used as the baseline BPA. Change in BPA was computed using BPA at 1 day after the second dental treatment minus BPA at baseline. The second dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically 3-4 weeks after the first dental treatment. Analysis of change in BPA was done using the arithmetic mean. |
| Change in Urinary Bisphenol A Level (BPA) From Baseline to 14 Days After the Second Dental Treatment | From Baseline to 14 days after the second dental treatment (The second dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically 3-4 weeks after the first dental treatment.) | BPA was measured, corrected for specific gravity, in ng/mL. We corrected BPA for specific gravity (SG) using the formula: BPA \* \[(meanSG - 1)/(SG - 1)\], where meanSG is the mean of the SG for the samples examined. Urine samples were collected twice pre-treatment and the geometric mean of BPA at each pre-treatment visit was used as the baseline BPA. Change in BPA was computed using BPA at 14 days after the second dental treatment minus BPA at baseline. The second dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically 3-4 weeks after the first dental treatment. Analysis of change in BPA was done using the arithmetic mean. |
Countries
United States
Participant flow
Recruitment details
A total of 113 children aged 3-17 were enrolled in Composites and Urinary Bisphenol-A Study (CUBS) across 8 dental clinics in Massachusetts between February 2012 and December 2013. Follow-up visits were completed in June 2014.
Participants by arm
| Arm | Count |
|---|---|
| Composite Restoration of dental caries with dental composite: Dental Restoration (bisphenol A diglycidyl ether methacrylate based composite) | 98 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Difficulty with time commitment | 2 |
| Overall Study | Ineligible | 1 |
| Overall Study | Lost to Follow-up | 8 |
| Overall Study | No post-treatment urine sample collected | 10 |
| Overall Study | No pre-treatment urine sample collected | 1 |
Baseline characteristics
| Characteristic | Composite |
|---|---|
| Age, Continuous | 9.36 Years STANDARD_DEVIATION 3.75 |
| Race/Ethnicity, Customized Black - Non Hispanic | 19 participants |
| Race/Ethnicity, Customized Hispanic | 38 participants |
| Race/Ethnicity, Customized Other | 14 participants |
| Race/Ethnicity, Customized White - Non Hispanic | 27 participants |
| Sex: Female, Male Female | 46 Participants |
| Sex: Female, Male Male | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 91 |
| serious Total, serious adverse events | 0 / 91 |
Outcome results
Primary
Change in Urinary Bisphenol A Level (BPA) From Baseline to 14 Days After the First Dental Treatment
BPA was measured, corrected for specific gravity, in ng/mL. We corrected BPA for specific gravity (SG) using the formula: BPA \* \[(meanSG - 1)/(SG - 1)\], where meanSG is the mean of the SG for the samples examined. Urine samples were collected twice pre-treatment and the geometric mean of BPA at each pre-treatment visit was used as the baseline BPA. Change in BPA was computed using BPA at 14 days after the first dental treatment minus BPA at baseline. The first dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically within a few weeks of baseline. Analysis of change in BPA was done using the arithmetic mean.
Time frame: From Baseline to 14 days after the first dental treatment (The first dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically within a few weeks of baseline.)
Population: Of 91 subjects who had at least one pre-treatment and at least one post-treatment urine sample, 81 subjects who had BPA at 14 days after the first dental treatment were used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Composite | Change in Urinary Bisphenol A Level (BPA) From Baseline to 14 Days After the First Dental Treatment | -0.50 ng/mL | Standard Deviation 4.09 |
Comparison: One sample t-test was used to test whether the mean change from baseline was different from 0.p-value: 0.27t-test, 2 sided
Comparison: To see the association between composite exposure on all surfaces and change in BPA from baseline to 14 days after the first treatment, the linear model was used with the change in BPA outcome. Log-transformed BPA was used for the analysis. Composite exposure on all surfaces was used as the main predictor.p-value: 0.4895% CI: [-0.258, 0.123]Regression, Linear
Comparison: To see the association between composite exposure on posterior occlusal surfaces and change in BPA from baseline to 14 days after the first treatment, the linear model was used with the change in BPA outcome. Log-transformed BPA was used for the analysis. Composite exposure on posterior occlusal surfaces was used as the main predictor.p-value: 0.50195% CI: [-0.293, 0.145]Regression, Linear
Primary
Change in Urinary Bisphenol A Level (BPA) From Baseline to 14 Days After the Second Dental Treatment
BPA was measured, corrected for specific gravity, in ng/mL. We corrected BPA for specific gravity (SG) using the formula: BPA \* \[(meanSG - 1)/(SG - 1)\], where meanSG is the mean of the SG for the samples examined. Urine samples were collected twice pre-treatment and the geometric mean of BPA at each pre-treatment visit was used as the baseline BPA. Change in BPA was computed using BPA at 14 days after the second dental treatment minus BPA at baseline. The second dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically 3-4 weeks after the first dental treatment. Analysis of change in BPA was done using the arithmetic mean.
Time frame: From Baseline to 14 days after the second dental treatment (The second dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically 3-4 weeks after the first dental treatment.)
Population: Of 91 subjects who had at least one pre-treatment and at least one post-treatment urine sample, 15 subjects who had BPA at 14 days after the second dental treatment were used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Composite | Change in Urinary Bisphenol A Level (BPA) From Baseline to 14 Days After the Second Dental Treatment | -0.28 ng/mL | Standard Deviation 3.55 |
Comparison: One sample t-test was used to test whether the mean change from baseline was different from 0.p-value: 0.76t-test, 2 sided
Comparison: To see the association between composite exposure on all surfaces and change in BPA from baseline to 14 days after the second treatment, the linear model was used with the change in BPA outcome. Log-transformed BPA was used for the analysis. Composite exposure on all surfaces was used as the main predictor.p-value: 0.96895% CI: [-1.061, 1.025]Regression, Linear
Comparison: To see the association between composite exposure on posterior occlusal surfaces and change in BPA from baseline to 14 days after the second treatment, the linear model was used with the change in BPA outcome. Log-transformed BPA was used for the analysis. Composite exposure on posterior occlusal surfaces was used as the main predictor.p-value: 0.82295% CI: [-0.941, 0.775]Regression, Linear
Primary
Change in Urinary Bisphenol A Level (BPA) From Baseline to 1 Day After the First Dental Treatment
BPA was measured, corrected for specific gravity, in ng/mL. We corrected BPA for specific gravity (SG) using the formula: BPA \* \[(meanSG - 1)/(SG - 1)\], where meanSG is the mean of the SG for the samples examined. Urine samples were collected twice pre-treatment and the geometric mean of BPA at each pre-treatment visit was used as the baseline BPA. Change in BPA was computed using BPA at 1 day after the first dental treatment minus BPA at baseline. The first dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically within a few weeks of baseline. Analysis of change in BPA was done using the arithmetic mean.
Time frame: From Baseline to 1 day after the first dental treatment (The first dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically within a few weeks of baseline.)
Population: Of 91 subjects who had at least one pre-treatment and at least one post-treatment urine sample, 89 subjects who had BPA at 1 day after the first dental treatment were used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Composite | Change in Urinary Bisphenol A Level (BPA) From Baseline to 1 Day After the First Dental Treatment | 1.71 ng/mL | Standard Deviation 9.94 |
Comparison: One sample t-test was used to test whether the mean change from baseline was different from 0.p-value: 0.11t-test, 2 sided
Comparison: To see the association between composite exposure on all surfaces and change in BPA from baseline to 1 day after the first treatment, the linear model was used with the change in BPA outcome. Log-transformed BPA was used for the analysis. Composite exposure on all surfaces was used as the main predictor.p-value: 0.00395% CI: [0.105, 0.494]Regression, Linear
Comparison: To see the association between composite exposure on posterior occlusal surfaces and change in BPA from baseline to 1 day after the first treatment, the linear model was used with the change in BPA outcome. Log-transformed BPA was used for the analysis. Composite exposure on posterior occlusal surfaces was used as the main predictor.p-value: 0.00295% CI: [0.145, 0.585]Regression, Linear
Primary
Change in Urinary Bisphenol A Level (BPA) From Baseline to 1 Day After the Second Dental Treatment
BPA was measured, corrected for specific gravity, in ng/mL. We corrected BPA for specific gravity (SG) using the formula: BPA \* \[(meanSG - 1)/(SG - 1)\], where meanSG is the mean of the SG for the samples examined. Urine samples were collected twice pre-treatment and the geometric mean of BPA at each pre-treatment visit was used as the baseline BPA. Change in BPA was computed using BPA at 1 day after the second dental treatment minus BPA at baseline. The second dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically 3-4 weeks after the first dental treatment. Analysis of change in BPA was done using the arithmetic mean.
Time frame: From Baseline to 1 day after the second dental treatment (The second dental treatment was scheduled as per treatment needs and the schedules of the dentist and patient. It was typically 3-4 weeks after the first dental treatment.)
Population: Of 91 subjects who had at least one pre-treatment and at least one post-treatment urine sample, 26 subjects who had BPA at 1 day after the second dental treatment were used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Composite | Change in Urinary Bisphenol A Level (BPA) From Baseline to 1 Day After the Second Dental Treatment | -0.59 ng/mL | Standard Deviation 3.62 |
Comparison: One sample t-test was used to test whether the mean change from baseline was different from 0.p-value: 0.41t-test, 2 sided
Comparison: To see the association between composite exposure on all surfaces and change in BPA from baseline to 1 day after the second treatment, the linear model was used with the change in BPA outcome. Log-transformed BPA was used for the analysis. Composite exposure on all surfaces was used as the main predictor.p-value: 0.61295% CI: [-0.418, 0.254]Regression, Linear
Comparison: To see the association between composite exposure on posterior occlusal surfaces and change in BPA from baseline to 1 day after the second treatment, the linear model was used with the change in BPA outcome. Log-transformed BPA was used for the analysis. Composite exposure on posterior occlusal surfaces was used as the main predictor.p-value: 0.69695% CI: [-0.339, 0.495]Regression, Linear
Primary
Change in Urinary Bisphenol A Level (BPA) From Baseline to 6 Months
BPA was measured, corrected for specific gravity, in ng/mL. We corrected BPA for specific gravity (SG) using the formula: BPA \* \[(meanSG - 1)/(SG - 1)\], where meanSG is the mean of the SG for the samples examined. Urine samples were collected twice pre-treatment and the geometric mean of BPA at each pre-treatment visit was used as the baseline BPA. Change in BPA was computed using BPA at follow-up minus BPA at baseline. Analysis of change in BPA was done using the arithmetic mean.
Time frame: From Baseline to 6 months
Population: Of 91 subjects who had at least one pre-treatment and at least one post-treatment urine sample, 77 subjects who had BPA at 6 months were used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Composite | Change in Urinary Bisphenol A Level (BPA) From Baseline to 6 Months | 0.29 ng/mL | Standard Deviation 4.66 |
Comparison: One sample t-test was used to test whether the mean change from baseline to 6 months was different from 0.p-value: 0.58t-test, 2 sided
Comparison: To see the association between composite exposure on all surfaces and change in BPA from baseline to 6 months, the linear model was used with the change in BPA outcome. Log-transformed BPA was used for the analysis. Composite exposure on all surfaces was used as the main predictor.p-value: 0.40695% CI: [-0.206, 0.084]Regression, Linear
Comparison: To see the longitudinal association between composite exposure on all surfaces and change in BPA from baseline, the repeated measure model was used with all available follow-up BPA data. Log-transformed BPA was used for the analysis. Composite exposure on all surfaces was used as the main predictor.p-value: 0.69395% CI: [-0.101, 0.067]Mixed Models Analysis
Comparison: To see the association between composite exposure on posterior occlusal surfaces and change in BPA from baseline to 6 months, the linear model was used with the change in BPA outcome. Log-transformed BPA was used for the analysis. Composite exposure on posterior occlusal surfaces was used as the main predictor.p-value: 0.1695% CI: [-0.296, 0.05]Regression, Linear
Comparison: To see the longitudinal association between composite exposure on posterior occlusal surfaces and change in BPA from baseline, the repeated measure model was used with all available follow-up BPA data. Log-transformed BPA was used for the analysis. Composite exposure on posterior occlusal surfaces was used as the main predictor.p-value: 0.57495% CI: [-0.131, 0.073]Mixed Models Analysis