MI Varnish and MI Paste Plus in a Caries Prevention and Remineralization Study

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.

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.