SmartMouth Advanced Clinical Formula Clinical Research Design Protocol

Study Population A 10 week double-blinded, randomized clinical study will be conducted on 80
subjects diagnosed with plaque induced gingivitis and/or chronic periodontitis. The study
will take place at Saint Louis University Center for Advanced Dental Education and Southern
Illinois University School of Dental Medicine.

Research Design and Methods Visit 1 Subjects who sign the informed consent and medical
history forms and meet the preliminary entrance criteria will be examined at baseline. All
participants will be informed of the nature of the study, its purpose, and any possible
risks. Subjects will also be informed as to the length of the study and the specific
procedures that will be carried out. Subjects will be informed that this is a voluntary study
and that they are free to withdraw from the study at any time.

Clinical measurements of plaque and gingival indices will be taken. A gingival bleeding score
will be determined. Examiners will be standardized for scoring.

Gingival index (GI) will be measured using the Loe and Silness method (Loe and Silness 1963).
The gingiva will be scored at six sites of each tooth (distobuccal, buccal, mesiobuccal,
distolingual, lingual, mesiolingual) and given a score from 0 - 3. By adding the scores and
dividing by the total number of sites, the GI for the patient will be obtained. The following
criteria will be used for scoring:

0 - Absence of inflammation

1. - Mild inflammation: slight change in color, slight edema; no bleeding upon probing

2. - Moderate inflammation: Redness, edema, and glazing; bleeding upon probing

3. - Severe inflammation: Marked redness and edema; ulceration; tendency to spontaneous
bleeding Sites with GI scores of 2 or 3 will be counted as bleeding. A whole mouth total
gingival bleeding score will be calculated by summing the number of bleeding sites and
dividing by the number of teeth.

Plaque will be scored based on the Turesky modification of the Quigley—Hein Plaque Index (PI)
(Turesky 1970). A score of 0 - 5 will be assigned to six sites of each tooth (distobuccal,
buccal, mesiobuccal, distolingual, lingual, mesiolingual) following the use of a disclosing
solution. The following criteria will be used:

0 - No plaque

1. - Isolated areas of plaque at gingival margin

2. - Thin continuous band of plaque at gingival margin (up to 1 mm)

3. - Band of plaque ˃ 1 mm and ˂ 1/3 of the tooth surface

4. - Plaque covering 1/3 to ˂ 2/3 of tooth surface

5. - Plaque covering ≥ 2/3 of tooth surface The Plaque Index for the entire mouth will be
determined by dividing the total score by the number of surfaces examined.

The Gingival Index will be measured prior to the Plaque Index. Teeth with gross caries and
third molars will not be scored with either index.

Extrinsic tooth stain will be scored on the facial surfaces of the 8 incisor teeth using a
modification of the Lobene tooth stain index (SI) (Lobene 1968). Each incisor will be scored
for stain area on a scale of 0-3. The sum of the stain scores for the subject will be used as
that subject's stain score. Scores will be recorded from 0 to 3 as follows:

0: no stain detected, only tooth color

1. stain over 1/3 of the surface

2. stain over 2/3 of the surface

3. stain over more than 2/3 of the surface Supragingival calculus on the lingual surfaces
of the six mandibular anterior teeth will be scored using the Volpe-Manhold calculus
index (CI) (Volpe et al. 1965). The supragingival calculus in three defined planes on
the lingual surface of each tooth will be measured using a periodontal probe. The
measurements will be added and a mean subject score will be calculated.

A complete periodontal examination will be performed for all subjects that meet the inclusion
criteria. A panoramic radiograph will be taken for all subjects that do not have full mouth
radiographs within the last year.

Safety assessments will be made at each measurement visit. Assessment of the oral soft
tissues will be conducted at each visit by visual examination of the oral cavity. All areas
will be assessed and reported as normal or abnormal.

Subject compensation: all subjects entered into the study will be given a gift card at the
end of visit 2, visit 3 and visit 4.

Visit 2 Visit 2 will occur within 4 weeks of Visit 1. Subjects entered into the study will be
randomly assigned to three groups: Group 1 (Smart Mouth ACF), Group 2 (0.12% chlorhexidine)
or Group 3 (placebo). All subjects will be given a complete dental prophylaxis to remove
plaque, calculus, and stain. Written and verbal oral hygiene instructions will be given that
include a regular regimen of brushing twice daily and flossing daily. All subjects will be
assigned a commercially available ADA accepted toothbrush and dental floss. They will be
given a 3 week supply of the assigned mouthrinse with written and verbal instructions for
use. Subjects will be instructed not to have their teeth professionally cleaned prior to
study completion.

All mouthrinses will be in a plain package and dispensed by the faculty investigators. The
package will be labeled with a code to indicate the product. Only the faculty investigators
will have access to the code information. Directions for use will be contained in the
package. The examiners will not see the product. The examiners will give instructions for
mouthrinse use, but they will not be aware which rinse the subjects are using. Each product
will contain two solutions which are mixed prior to use.

Visit 3 Subjects will be examined 3 weeks after visit 2. All clinical measurements will be
repeated. Each subject will return with any unused rinse or two empty bottles of rinse.
Compliance will be determined by regulating the amount of rinse dispensed on a 3 week basis
and by the measurement of any unused rinse at the end of two 3 week periods. Additional rinse
will be given to each subject after visit 3 for use until the final visit.

Visit 4 Subjects will be examined 3 weeks after visit 3 (6 weeks from visit 2). Clinical
measurements will be repeated. Each subject will return with any unused rinse or two empty
bottles of rinse. Compliance will be determined by the measurement of any unused rinse at the
end of the study.

Subjects will be given a survey to answer questions about their experience with the
mouthrinse. Prophylaxis may be performed at this visit.

Following the study, the subjects will be treated by their provider's discretion.

Inclusion Criteria:

- Subjects between the ages of 18 to 80

- Subjects with a diagnosis of gingivitis or chronic periodontitis

- Entry levels of gingival inflammation and plaque accumulation will be present (mean
Gingival Index ≥ 0.4 and Plaque Index ≥ 1.0)

- Subjects that are in good medical health at time of the study

- At least 20 permanent natural teeth

Exclusion Criteria:

- Use of local or systemic antibiotics during the course of the study

- Subjects that are pregnant or nursing mothers

- Subjects undergoing orthodontic therapy

- Subjects wearing removable prostheses

- Subjects taking medication which is altering the gingiva or causing inflammation

- Gingival overgrowth

- History of sensitivity or suspected allergies following the use of oral hygiene
products

- Subjects taking anti-inflammatory or anticoagulant medications that would alter the
gingiva and promote bleeding

- Subjects that require antibiotic prophylaxis prior to dental treatment

- Subjects that have acute dental problems requiring immediate treatment