GC-WS: MI Varnish and MI Paste Plus in a Caries Prevention and Remineralization Study

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT02424097
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 41
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The objective of this clinical study is to evaluate the efficacy of multiple applications of MI Varnish in combination with MI Paste Plus in caries protection and remineralization in comparison to the use of a control (Crest 1,100ppm Fluoride tooth paste, Fluoride rinse recommendation) in orthodontic patients in a randomized, single blind, prospective, controlled clinical trial over 12 months.

The effect will be measured by white spot lesion regression and prevention as lesion count. Lesions will be scored using the Enamel Decalcification Index (EDI) area evaluation scheme (primary outcome), International Caries Detection and Assessment System (ICDAS), the caries lesion activity criteria (Nyvad criteria; Bente Nyvad, Scandinavian Researcher), and Quantitative Light Fluorescence (QLF, Inspektor Pro, Netherlands)/SOPROLIFE (SOPROLIFE fluorescence camera system, Acteon, France) evaluation in maxillary and mandibular anterior teeth with orthodontic brackets in treatment and control groups.

Condition or Disease	Intervention/Treatment	Phase
Dental White Spots; Dental Caries	Drug: CPP-ACP 5% sodium fluoride varnish & 900ppm fluoride paste; Drug: 1,100pm F-toothpaste and 0.5%NaF rinse	Phase 4

Detailed Description

The study is designed as randomized, single blind, prospective, clinical trial over 12 months. The subjects for this study will be recruited from the University of California at San Francisco UCSF, School of Dentistry, Orthodontic Clinic.

Participants in the study will be patients, who are in orthodontic treatment or will start orthodontic treatment; subjects must have full fixed appliances, with brackets bonded to the buccal surfaces of the maxillary and mandibular incisors, canines and first bicuspids. Subjects will be of moderate or high caries risk according to Caries Risk Assessment and ATP (Adenosine triphosphate) bacteria testing. Subjects will present with at least two active white spot lesions on his/her anterior teeth at the start of the study. The age limitation is ≥ 11 years.

The subjects will be randomly assigned to 1) Experimental group: MI Varnish and MI Paste Plus or 2) Control standard of care group: 1,100 ppm Fluoride tooth paste and recommendation to use OTC (Over-the-counter) Fluoride-rinse in the evening at home.

The clinical study investigator will evaluate the labial/buccal surfaces of upper and lower anterior teeth (first bicuspid to first bicuspid) for white spot lesions (WSL) at baseline and at the end of 3, 6, and 12 months. Newly formed lesions and changes in existing white spot lesions will be documented (using Enamel Decalcification Index (EDI), ICDAS II, light digital photographs and blue fluorescence photography SOPROLIFE and QLF- Quantitative Light Fluorescence).

All subjects will receive one professional tooth cleaning at baseline and at each other evaluation office visit to allow WSL evaluation (cleaning with ultrasonic device, and prophylaxis brush) and treatment application.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Prevention
• Official Title: MI Varnish and MI Paste Plus in a Caries Prevention and Remineralization Study
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MI Paste & MI Varnish MI past will be applied by the patient every night; MI varnish will be applied every three months in the office	Drug: CPP-ACP 5% sodium fluoride varnish & 900ppm fluoride paste; MI Paste & MI Varnish- in-office: varnish application once every 3 months; at baseline, at the end of month 3, 6, and 9 (4 applications) - at-home: brushing with regular 1,100ppm F-toothpaste, 2x per day and MI Paste Plus, home application after brushing in the evening; 3-5 minutes with in-home application tray
Active Comparator: Standard of Care Subjects will use at home regal toothpaste every night and F-mouth rinse as recommended	Drug: 1,100pm F-toothpaste and 0.5%NaF rinse; Standard of care at-home: Crest tooth brushing 2x per day - (recommendation OTC Fluoride-rinse in the evening at home 1x per day)

Outcome Measures

Primary Outcome Measures

1. Change in White Spot Lesions Count - Enamel Decalcification Index (EDI) [Baseline and 12-months]

   The area evaluation scheme of the Enamel Decalcification Index (EDI) divides the buccal surface of each tooth into 4 quadrants and then registers the possible existence of a white spot lesion (decalcification) in each of these 4 quadrants. For each quadrant the lesion can be scaled as: 0 = no decalcification, 1 = decalcification covering <50% of the area, 2 = decalcification covering > 50% of the area, 3 = decalcifications covering 100% of the area or severe decalcification with cavitation. Thus, for each tooth the value can range between 0 and 12. 16 teeth per subject were evaluated, for each subject the value of each tooth was added - thus the range per one subject can be between 0 and 192. A mean over all participants in one group was calculated. A higher score means a worse outcome.

Secondary Outcome Measures

1. Change in International Caries Detection and Assessment System (ICDAS II) to Score for Smooth Surfaces White Spot Lesions (WSL) [Baseline and 12-months]

   The International Caries Detection and Assessment System (ICDAS II) is a standardized method of caries lesion assessment.The score is based on apparent lesion severity, with scores from 0 to 6.The buccal surface of each tooth was divided into 4 quadrants, and for each quadrant a score was assigned with ICDAS scores: 0 = sound, 1 = first visual change in enamel, after air drying, 2 = distinct demineralization visual change in enamel, 3 = localized enamel breakdown due to caries with no visible dentin, 4 = surface with underlying dark shadow from dentin with or without enamel breakdown, 5 = distinct cavity with visible dentin, 6 = extensive cavity with visible dentin. The ICDAS scores were calculated as the sum of the highest ICDAS scores assigned to each examined tooth per subject. 16 teeth per subject were evaluated, thus, for each subject the value can range between 0 and 96. A mean over all participants in one group was calculated. A higher score means a worse outcome.

Other Outcome Measures

1. Change in Lesion Activity, Nyvad Criteria [Baseline and 12-months]

   WS lesion activity will be determined using the Nyvad criteria;

2. Change in SOPROLIFE [Baseline and 12-months]

   fluorescence measurements using blue light fluorescence make WSLs visible for scoring;

3. Change in Quantitative Light Fluorescence (QLF) [Baseline and 12-months]

   Quantitative Light Fluorescence will be used to evaluate the WSL

Eligibility Criteria

Criteria

• Ages Eligible for Study: 11 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• age 11 or older,

• good health,

• either gender

• present with at least two active white spot lesions on his/her anterior teeth at the start of the study

• have a moderate or high caries risk according to CAMBRA (Caries Management By Risk Assessment) rules

• require at least 12 additional months of full fixed appliance therapy from the time they are recruited for the study

• able to cooperate for treatment in the dental chair and follow at-home instructions

• have an understanding of the study

• willing to comply with all study procedures and protocols

• patient participant is able to provide written informed consent in English; if the participant is a minor, the parent/guardian is able to provide written informed consent in English and the patient participant is able to provide written assent in English

• patient participant or if a minor, the parent/guardian, is willing to sign the "Authorization for Release of Personal Health Information and Use of Personally Unidentified Study Data for Research" form; data will only be used for research

• verifiable records of bonding with Transbond Plus Self-Etching Primer (3M Unitek, Monrovia, CA) and Transbond Light Cure Adhesive or similar products

• verifiable records that "ProSeal" has not been applied at any time during the orthodontic treatment

Exclusion Criteria:

• untreated cavitated lesions

• extensive composite fillings on buccal surfaces of front teeth/first bicuspids or more than one dental crown on front teeth/first bicuspids

• has sealants or fluoride releasing cements on the buccal surface of the anterior teeth

• in-office fluoride treatment in the last three months

• history of using any products containing CCP-ACP (casein phosphopeptides and amorphous calcium phosphate; MI paste, chewing gums or candies, etc.), prescription Fluoride products, and Chlorhexidine use in the last three months

• intrinsic or extremely heavy extrinsic staining

• any signs of fluorosis in the dentition

• any signs of morphologic/anatomical/developmental deviations in the teeth

• previous history of in office bleaching treatment

• subject not willing to stop the use of any other oral hygiene product than those prescribed/suggested

• has underlying systemic disease which could alter enamel composition or formation

• suffering from systemic diseases, significant past or medical history with conditions that may affect oral health or oral flora (i.e. diabetes, HIV, heart conditions that require antibiotic prophylaxis)

• use of medication causing dry mouth (extreme high caries risk)

• subject is pregnant or lactating

• milk protein allergy

• any illness/condition that the investigator feels will affect the study outcome

• will leave the area and will not be available for recall visits

• subjects who are not willing to inform us about prospective visits of other dentist and will not allow us to discuss treatment with those dentist

• subjects who are not willing to refrain from any additional professional tooth cleaning or any additional Fluoride application.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF School of Dentistry - Dental Offices in Bay Area	San Francisco	California	United States	94143

Sponsors and Collaborators

• University of California, San Francisco

Investigators

• Principal Investigator: Peter Rechmann, DMD, PhD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02424097
• Other Study ID Numbers: GCAmerica-WS
• First Posted: Apr 22, 2015
• Last Update Posted: Apr 22, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of California, San Francisco: Prevention
• Additional relevant MeSH terms: Dental Caries; Listerine; Fluorides; Sodium Fluoride; Fluorides, Topical

Study Results

Participant Flow

Arm/Group Title	MI Paste & MI Varnish	Standard of Care
Arm/Group Description	MI past will be applied by the patient every night; MI varnish will be applied every three months in the office CPP-ACP 5% sodium fluoride varnish & 900ppm fluoride paste: MI Paste & MI Varnish- in-office: varnish application once every 3 months; at baseline, at the end of month 3, 6, and 9 (4 applications) - at-home: brushing with regular 1,100ppm F-toothpaste, 2x per day and MI Paste Plus, home application after brushing in the evening; 3-5 minutes with in-home application tray	Subjects will use at home regal toothpaste every night and F-mouth rinse as recommended 1,100pm F-toothpaste and 0.5%NaF rinse: Standard of care at-home: Crest tooth brushing 2x per day - (recommendation OTC Fluoride-rinse in the evening at home 1x per day)
Period Title: Overall Study
STARTED	20	20
COMPLETED	19	18
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	MI Paste & MI Varnish	Standard of Care	Total
Arm/Group Description	MI past will be applied by the patient every night; MI varnish will be applied every three months in the office CPP-ACP 5% sodium fluoride varnish & 900ppm fluoride paste: MI Paste & MI Varnish- in-office: varnish application once every 3 months; at baseline, at the end of month 3, 6, and 9 (4 applications) - at-home: brushing with regular 1,100ppm F-toothpaste, 2x per day and MI Paste Plus, home application after brushing in the evening; 3-5 minutes with in-home application tray	Subjects will use at home regal toothpaste every night and F-mouth rinse as recommended 1,100pm F-toothpaste and 0.5%NaF rinse: Standard of care at-home: Crest tooth brushing 2x per day - (recommendation OTC Fluoride-rinse in the evening at home 1x per day)	Total of all reporting groups
Overall Participants	20	20	40
Age (Count of Participants)
<=18 years	17 85%	17 85%	34 85%
Between 18 and 65 years	3 15%	3 15%	6 15%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.1 (3.8)	16.5 (3.8)	16.1 (3.8)
Sex: Female, Male (Count of Participants)
Female	11 55%	8 40%	19 47.5%
Male	9 45%	12 60%	21 52.5%
Region of Enrollment (participants) [Number]
United States	20 100%	20 100%	40 100%

Outcome Measures

1. Primary Outcome

Title	Change in White Spot Lesions Count - Enamel Decalcification Index (EDI)
Description	The area evaluation scheme of the Enamel Decalcification Index (EDI) divides the buccal surface of each tooth into 4 quadrants and then registers the possible existence of a white spot lesion (decalcification) in each of these 4 quadrants. For each quadrant the lesion can be scaled as: 0 = no decalcification, 1 = decalcification covering <50% of the area, 2 = decalcification covering > 50% of the area, 3 = decalcifications covering 100% of the area or severe decalcification with cavitation. Thus, for each tooth the value can range between 0 and 12. 16 teeth per subject were evaluated, for each subject the value of each tooth was added - thus the range per one subject can be between 0 and 192. A mean over all participants in one group was calculated. A higher score means a worse outcome.
Time Frame	Baseline and 12-months

Outcome Measure Data

Analysis Population Description

enamel decalcification index (EDI)

Arm/Group Title	MI Paste & MI Varnish	Standard of Care
Arm/Group Description	MI past will be applied by the patient every night; MI varnish will be applied every three months in the office CPP-ACP 5% sodium fluoride varnish & 900ppm fluoride paste: MI Paste & MI Varnish- in-office: varnish application once every 3 months; at baseline, at the end of month 3, 6, and 9 (4 applications) - at-home: brushing with regular 1,100ppm F-toothpaste, 2x per day and MI Paste Plus, home application after brushing in the evening; 3-5 minutes with in-home application tray	Subjects will use at home regal toothpaste every night and F-mouth rinse as recommended 1,100pm F-toothpaste and 0.5%NaF rinse: Standard of care at-home: Crest tooth brushing 2x per day - (recommendation OTC Fluoride-rinse in the evening at home 1x per day)
Measure Participants	19	18
Mean (Standard Deviation) [units on a scale]	40.2 (13.6)	41.3 (11.8)

2. Secondary Outcome

Title	Change in International Caries Detection and Assessment System (ICDAS II) to Score for Smooth Surfaces White Spot Lesions (WSL)
Description	The International Caries Detection and Assessment System (ICDAS II) is a standardized method of caries lesion assessment.The score is based on apparent lesion severity, with scores from 0 to 6.The buccal surface of each tooth was divided into 4 quadrants, and for each quadrant a score was assigned with ICDAS scores: 0 = sound, 1 = first visual change in enamel, after air drying, 2 = distinct demineralization visual change in enamel, 3 = localized enamel breakdown due to caries with no visible dentin, 4 = surface with underlying dark shadow from dentin with or without enamel breakdown, 5 = distinct cavity with visible dentin, 6 = extensive cavity with visible dentin. The ICDAS scores were calculated as the sum of the highest ICDAS scores assigned to each examined tooth per subject. 16 teeth per subject were evaluated, thus, for each subject the value can range between 0 and 96. A mean over all participants in one group was calculated. A higher score means a worse outcome.
Time Frame	Baseline and 12-months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MI Paste & MI Varnish	Standard of Care
Arm/Group Description	MI past will be applied by the patient every night; MI varnish will be applied every three months in the office CPP-ACP 5% sodium fluoride varnish & 900ppm fluoride paste: MI Paste & MI Varnish- in-office: varnish application once every 3 months; at baseline, at the end of month 3, 6, and 9 (4 applications) - at-home: brushing with regular 1,100ppm F-toothpaste, 2x per day and MI Paste Plus, home application after brushing in the evening; 3-5 minutes with in-home application tray	Subjects will use at home regal toothpaste every night and F-mouth rinse as recommended 1,100pm F-toothpaste and 0.5%NaF rinse: Standard of care at-home: Crest tooth brushing 2x per day - (recommendation OTC Fluoride-rinse in the evening at home 1x per day)
Measure Participants	19	18
Mean (Standard Deviation) [score on a scale]	22.3 (5.9)	22.6 (4.9)

3. Other Pre-specified Outcome

Title	Change in Lesion Activity, Nyvad Criteria
Description	WS lesion activity will be determined using the Nyvad criteria;
Time Frame	Baseline and 12-months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Change in SOPROLIFE
Description	fluorescence measurements using blue light fluorescence make WSLs visible for scoring;
Time Frame	Baseline and 12-months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Change in Quantitative Light Fluorescence (QLF)
Description	Quantitative Light Fluorescence will be used to evaluate the WSL
Time Frame	Baseline and 12-months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	1 year, 8 months
Arm/Group Title	MI Paste & MI Varnish		Standard of Care
Arm/Group Description	MI past will be applied by the patient every night; MI varnish will be applied every three months in the office CPP-ACP 5% sodium fluoride varnish & 900ppm fluoride paste: MI Paste & MI Varnish- in-office: varnish application once every 3 months; at baseline, at the end of month 3, 6, and 9 (4 applications) - at-home: brushing with regular 1,100ppm F-toothpaste, 2x per day and MI Paste Plus, home application after brushing in the evening; 3-5 minutes with in-home application tray		Subjects will use at home regal toothpaste every night and F-mouth rinse as recommended 1,100pm F-toothpaste and 0.5%NaF rinse: Standard of care at-home: Crest tooth brushing 2x per day - (recommendation OTC Fluoride-rinse in the evening at home 1x per day)
All Cause Mortality
	MI Paste & MI Varnish		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Serious Adverse Events
	MI Paste & MI Varnish		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	MI Paste & MI Varnish		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.