Prevention of Enamel Demineralization by Use of K18-smooth Surface Sealant

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT03306433
• Collaborator: University of Colorado School of Dental Medicine (Other)
• Enrollment: 16
• Location: 1
• Arms: 3
• Actual Duration (Months): 10.9
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

This study will evaluate effectiveness of a urethane dimethacrylate (UDMA)-quaternary ammonium methacrylate (K18) resin (UDMA-K18) smooth surface sealant to prevent biofilm attachment to tooth surfaces thereby eliminating the possibility for the tooth to be demineralized. The hypothesis is that UDMA-K18 containing smooth surface sealant will be more effective at reducing enamel demineralization than the UDMA control or no treatment.

Condition or Disease	Intervention/Treatment	Phase
Dental Caries	Device: UDMA-K18 smooth surface sealant	N/A

Detailed Description

Esthetics is a motivating factor to seek orthodontic treatment. However, if oral hygiene is inadequate during fixed appliance wear, unsightly white spot lesions (WSL) may develop. WSLs are areas of enamel demineralization that develop due to microbial assault that manifest as white, chalky opacity on the enamel. Urethane dimethacrylate (UDMA) can be modified to produce an antimicrobial compound, UDMA-K18, that has been proven to decrease microbial attachment in-vitro. (Sticker 2016) The use of a UDMA-K18 containing sealant may help to eliminate the development of WSLs around orthodontic brackets.

This study will place experimental or control smooth surface resins on teeth that are scheduled to be extracted for orthodontic reasons. These teeth are typically bicuspids that are to be extracted to create room for the orthodontic movement of teeth. These teeth are usually not extracted at the advent of first orthodontic bracket bonding but are extracted about 30 days later. The design of this study is to place sealants on those teeth (or as control, no sealant) and evaluate the teeth after they have been extracted.

Design: The study is a prospective, paired randomized control trial for which treatment (no sealant, UDMA-control, or UDMA-K18 sealant) will be applied clinically and evaluated on extracted teeth in laboratory conditions.

Procedures: Before bonding, one premolar per patient will be assigned to a group. The group each premolar is assigned to will be determined by a randomized, computer generated program. The allocation will be concealed in an opaque envelope that will be opened at the time of initial bonding. If a fourth premolar is planned for extraction, a random selection of the treatments will be selected in a 1:1:1 ratio and this treatment will be applied to the fourth premolar.

At the time of initial bonding, the UDMA and UDMA-K18 sealant will be applied to the selected premolar following manufacturer instructions. Briefly, the clinician will isolate the teeth using the NOLA Dry Field System and excess saliva will be removed by drying the teeth with an air-water syringe. In the treatment group, 37 % Phosphoric Acid will be applied to the entire buccal surface for 30 seconds, rinsed, and dried. Next, the assigned sealant will be evenly applied to the entire buccal surface of the premolar and light cured. The sealant which is adhesive will be applied to the bracket pad and the bracket pad will be pushed to place, excess cement will be removed and light cured.

In the control group, 37 % Phosphoric Acid will be applied for 30 seconds strictly to the area where the bracket will be bonded on the buccal surface, rinsed, and dried. No sealant will be applied. The adhesive sealant will be applied to the bracket pad and the bracket pad will be pushed to place, excess cement will be removed and light cured. After 3-6 weeks, the patient will have their premolars extracted. After extraction they will be placed in a Tooth Storage Solution (25 % ethanol, 75 % water with the addition of saturated hydroxyapatite, 20 mg of NaN3, and 40 mg Thymol) that is antimicrobial and does not alter the tooth surface. These teeth will be collected by the investigators for histologic study.

The collected, extracted teeth will be sectioned using a water-cooled, Buhler slow speed diamond saw in three 2mm sections through the bracket base. A polarized light microscopy (PLM) digitized photograph of the cross-sectional sample will be analyzed to determine the depth of lesions, if present. The mineral density profile will be analyzed using contact micro radiography (TMR).

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: prospective, paired randomized control trial for which treatment (no sealant, UDMA control, UDMA-K18 sealant) will be applied clinically and evaluated on extracted teeth in laboratory conditions.prospective, paired randomized control trial for which treatment (no sealant, UDMA control, UDMA-K18 sealant) will be applied clinically and evaluated on extracted teeth in laboratory conditions.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The trial design is triple-blinded. The manufacturer will deliver the blinded treatments in identical bottles labelled A and B, therefore, neither the patient nor the clinician will know which treatment is rendered to each tooth. However, the no sealant control will not be blinded. Blinding will continue to be present during the histological portion of the experiment as the assessors will not be aware of which sealant was used to treat each tooth. After a blinded assessment, blinds will be lifted when between-group analysis is performed.
• Primary Purpose: Prevention
• Official Title: Prevention of Enamel Demineralization in Fixed Appliance Orthodontic Patients Using UDMA-K18 Sealant to Prevent Microbial Attachment Compared to a UDMA Control and no Sealant, a Randomized Split Mouth Clinical Trial
• Actual Study Start Date: Jan 8, 2018
• Actual Primary Completion Date: Dec 7, 2018
• Actual Study Completion Date: Dec 7, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: UDMA-K18 UDMA-K18 smooth surface sealant	Device: UDMA-K18 smooth surface sealant; The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.; Other Names: UDMA-control
Placebo Comparator: UDMA-control UDMA smooth surface sealant without K18	Device: UDMA-K18 smooth surface sealant; The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.; Other Names: UDMA-control
No Intervention: Negative control No intervention to provide baseline

Outcome Measures

Primary Outcome Measures

1. Change in Mineral Density Determined by the Canary Caries Detection System [Visit Window: 3-4 weeks.]

   The mineral density immediately below the surface of the tooth will lower if left unprotected to some extent.

Secondary Outcome Measures

1. White Spot Lesion (WSL) Index [Visit Window: 3-4 weeks.]

   The WSL Index is from 0 (no lesion) to 4 (severe lesion)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 89 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Orthodontic patients at the Department of Orthodontics Clinic, School of Dental Medicine, University of Colorado who agree to consent to this study.

• Orthodontic treatment plans that include fixed appliances from the second premolar to second premolar in both arches.

• Orthodontic treatment plans that include extractions of at least 3 bicuspids at about 1 month after bracket placement.

• The patient has adequate oral hygiene

Exclusion Criteria:

• Evidence of decalcification or restorations on any of the premolars planned for extraction prior to orthodontic treatment,

• Pregnant women (self reported)

• Any condition that contraindicates orthodontic treatment,

• Not willing to consent to the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado, School of Dental Medicine	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver
• University of Colorado School of Dental Medicine

Investigators

• Principal Investigator: Clifton Carey, PhD, Professor, Dir Translational Research, University of Colorado, School of Dental Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 14, 2017

More Information

Publications

• Gong SQ, Niu LN, Kemp LK, Yiu CK, Ryou H, Qi YP, Blizzard JD, Nikonov S, Brackett MG, Messer RL, Wu CD, Mao J, Bryan Brister L, Rueggeberg FA, Arola DD, Pashley DH, Tay FR. Quaternary ammonium silane-functionalized, methacrylate resin composition with antimicrobial activities and self-repair potential. Acta Biomater. 2012 Sep;8(9):3270-82. doi: 10.1016/j.actbio.2012.05.031. Epub 2012 May 29.
• Liu SY, Tonggu L, Niu LN, Gong SQ, Fan B, Wang L, Zhao JH, Huang C, Pashley DH, Tay FR. Antimicrobial activity of a quaternary ammonium methacryloxy silicate-containing acrylic resin: a randomised clinical trial. Sci Rep. 2016 Feb 23;6:21882. doi: 10.1038/srep21882.
• Schmuck BD, Carey CM. Improved Contact X-Ray Microradiographic Method to Measure Mineral Density of Hard Dental Tissues. J Res Natl Inst Stand Technol. 2010 Apr 1;115(2):75-83. Print 2010 Mar-Apr.
• Wefel JS, Harless JD. Comparison of artificial white spots by microradiography and polarized light microscopy. J Dent Res. 1984 Nov;63(11):1271-5.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT03306433
• Other Study ID Numbers: 17-0633
• First Posted: Oct 11, 2017
• Last Update Posted: Oct 7, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by University of Colorado, Denver: dental caries; white spot lesion; prevention; smooth surface sealant
• Additional relevant MeSH terms: Dental Caries

Study Results

Participant Flow

Recruitment Details	Recruitment began in January 2018 and ended in October 2018. Participants were recruited from the patient pool at the University of Colorado School of Dental Medicine Department of Orthodontics. Eligible candidates were offered the opportunity to participate in the study.
Pre-assignment Detail	Participants were enrolled into the study if they met the inclusion criteria of having a planned orthodontic therapy that required extraction of at least 2 teeth and that those teeth were free of demineralization and did not have restorations.

Arm/Group Title	All Participants
Arm/Group Description	Participants were enrolled into the study if they met the inclusion criteria of having a planned orthodontic therapy that required extraction of at least 2 teeth and that those teeth were free of demineralization and did not have restorations. Enrolled participants were assigned to receive up to all three treatments. There were 16 participant total. Treatments included: UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface. The adhesive used to bond the orthodontic bracket to the tooth UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.
Period Title: Overall Study
STARTED	16
UDMA-K18	12
Adhesive Control	12
UDMA-control	9
COMPLETED	9
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Participants were enrolled into the study if they met the inclusion criteria of having a planned orthodontic therapy that required extraction of at least 2 teeth and that those teeth were free of demineralization and did not have restorations. All 16 participants had all three treatments. Thus there were 16 participant total. Treatments included: UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface. The adhesive used to bond the orthodontic bracket to the tooth UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.
Overall Participants	16
Age (Years) [Mean (Standard Deviation) ]
Age	13.8 (2.3)
Sex: Female, Male (Count of Participants)
Female	8 50%
Male	8 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 68.8%
Not Hispanic or Latino	5 31.3%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%
Canary Score (Canary Numbers) [Mean (Full Range) ]
Mean (Full Range) [Canary Numbers]	7

Outcome Measures

1. Primary Outcome

Title	Change in Mineral Density Determined by the Canary Caries Detection System
Description	The mineral density immediately below the surface of the tooth will lower if left unprotected to some extent.
Time Frame	Visit Window: 3-4 weeks.

Outcome Measure Data

Analysis Population Description

In this split mouth (same mouth) design all participants receive all treatments.

Arm/Group Title	UDMA-K18	UDMA-control	Adhesive Control
Arm/Group Description	UDMA-K18 smooth surface sealant UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.	UDMA smooth surface sealant without K18 UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.	The adhesive used to bond the orthodontic bracket to the tooth
Measure Participants	12	9	12
Mean (Standard Deviation) [Canary Number]	23.424 (3.288)	31.125 (4.275)	35.563 (7.378)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UDMA-K18, Adhesive Control
	Comments	Paired difference test within each participant.
	Type of Statistical Test	Equivalence
	Comments	The null hypothesis is that there are no significant paired differences between the groups. The power calculation is based on the observed variation and number of participants
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	Paired difference p value comparing UDMA-K18 vs Adhesive Control
	Method	Paired difference test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Paired difference t-test
	Estimated Value	-12.139
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 7.101
	Estimation Comments	There are 12 participants (pairs) for this comparison

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	UDMA-K18, UDMA-control
	Comments	Paired comparison
	Type of Statistical Test	Equivalence
	Comments	Null hypothesis was that there were no differences between the groups
Statistical Test of Hypothesis	p-Value	0.0063
	Comments	Paired differrnce between UDMA-K18 and UDMA control
	Method	Paired difference test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Paired difference t-test
	Estimated Value	-7.412
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 6.049
	Estimation Comments	There are 9 participant pairs for this comparison

2. Secondary Outcome

Title	White Spot Lesion (WSL) Index
Description	The WSL Index is from 0 (no lesion) to 4 (severe lesion)
Time Frame	Visit Window: 3-4 weeks.

Outcome Measure Data

Analysis Population Description

Split mouth design : All participants received all treatments

Arm/Group Title	UDMA-K18	UDMA-control	Adhesive Control
Arm/Group Description	UDMA-K18 smooth surface sealant UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.	UDMA smooth surface sealant without K18 UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.	The adhesive used to bond the orthodontic bracket to the tooth
Measure Participants	12	9	12
Median (Full Range) [White spot Index]	0	2	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UDMA-K18, Adhesive Control
	Comments	WSL Index is non-parametric
	Type of Statistical Test	Equivalence
	Comments	The Null hypothesis was that there would be no differences between the groups
Statistical Test of Hypothesis	p-Value	0.0033
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Chi Square on WSL Index frequency
	Estimated Value	15.77
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	UDMA-K18, UDMA-control
	Comments
	Type of Statistical Test	Equivalence
	Comments	The null hypothesis was that there would not be any differences between the groups
Statistical Test of Hypothesis	p-Value	0.1450
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Chi Square on WSL Index frequency
	Estimated Value	6.8321
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	10 Months, January 2018 to October 2018
Adverse Event Reporting Description	Study participants were provided with a 24-hour hot line to call if they experienced any discomfort associated with the placement of the sealant or orthodontic bracket.
Arm/Group Title	UDMA-K18		UDMA-control		Adhesive Control
Arm/Group Description	UDMA-K18 smooth surface sealant UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.		UDMA smooth surface sealant without K18 UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.		The adhesive used to bond the orthodontic bracket to the tooth
All Cause Mortality
	UDMA-K18		UDMA-control		Adhesive Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)
Serious Adverse Events
	UDMA-K18		UDMA-control		Adhesive Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	UDMA-K18		UDMA-control		Adhesive Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.