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Clinical Studies -
Tooth Whitening
ADA
Seal of Acceptance Certification Study for
Discus Dental, Inc.
Efficacy of NITE WHITE with ACP® Whitening Gel: A Clinical Trial Final Report,
March 22, 1997
Investigation:
Susham Nachnani, MS
Lawrence E. Wolinsky, Ph.D., D.M.D.
Edmaond R. Hewlett, D.D.S.
Eric Kuo, D.D.S.
Todd C. Snyder, D.D.S.
Herman Choi, B.S.
University of California, Los Angeles UCLA
School of Dentistry
Clinical Research Center, CHS 33-064 Los Angeles, California 90095
PURPOSE
The
purpose of this study was to evaluate the clinical efficacy and
the duration of the efficacy of NITE WHITE with ACP® (NW) 10% carbamide peroxide
tooth whitening formulation, marketed by Discus Dental, against
placebo. This study followed the guidelines for testing peroxide-containing
oral hygiene products which were established by the ADA's Council
on Dental Therapeutics. A total of 47 subjects, each with a minimum
rating of A3 on the Vita® shade guide (n=24 for placebo group, n=23
for active group) were enrolled in this parallel, double-blinded,
two cell, randomized clinical trail. Subjects were directed by this
dentist to use the regimen for a minimum of 5 hours every night
for two weeks. Subjects were examined at baseline, day 1, day 7,
and day 14 during the active phase of the study. There were also
a 2 follow-up examinations of all subjects at approximately 3 months
and 6 months to assess the duration of efficacy. The data from baseline
to month 6 is being presented in this abstract. Enamel shade changes,
plaque index, gingival index, soft tissue effects, attached gingiva,
sensitivity, vitality and adverse events (gingival irritations)
were evaluated at all visits. Shade changes were evaluated using
both no statistically significant difference between the two groups
baseline shade values for teeth # 6, 7, 8, 9, 10, and 11. A statistically
significant difference between the two groups was found upon analysis
using the Fisher's exact test for the percentage of subjects who
experienced at least a 2 value decrease in shade between baseline
and two weeks and between baseline and 6 months. For teeth # 6,
7, 8, 9, 10, and 11,96% of the subjects in the active group experienced
at least a 2 value decrease in shade between baseline and 6 months,
while 29% of the subjects in the placebo group experienced a 2 value
decrease in shade. There was no statistically significant difference
between the placebo and active groups at baseline and day 14 between
baseline and 6-months for the measurement of pupal vitality, gingival
index, soft tissue evaluation and attached gingiva. This clinical
trial was supported by Discus Dental, Inc.
INTRODUCTION
Simplified procedures for dentist-prescribed, home -administered
vital teeth bleaching have heightened the public's interest in cosmetic
whitening. A wide range of tooth whitening products, both dentist-dispensed
and over-the-counter, has proliferated and flooded the market. Night
guard vital bleaching involves a custom mouth guard tray, which
is fabricated to keep a peroxide preparation or whitening agent
in intimate contact with the tooth surfaces. Dentist-prescribed
home teeth-whitening generally involves the use of 10% - 15% carbamide
peroxide or 1% - 10% hydrogen peroxide material. Ten percent carbamide
peroxide is roughly equivalent to 3% hydrogen peroxide and 7% urea.
Hydrogen peroxide is absorbed into the enamel and oxidezes the discolored
bodies within The tooth, causing a lightening effect.1-3
The clinical efficacy of these products is variable and depends
on the specific formulations. Thicker bleaching materials are retained
in the custom tray for longer periods of time. The presence of thickeners
such as Carbopol allows for a longer action which seems more advantageous
both in material conservation and efficacy. Some concern has been
expressed about the drying effects of the glycerin base on the enamel,
and taste has been a major deterrent for continued treatment for
some groups.
The purpose of this parallel, double-blinded, two cell, randomized
clinical study was to evaluate the clinical efficacy and the duration
of the efficacy of the tooth whitening formulation, NITE WHITE with ACPâ
marketed by Discus Dental, Inc., against a placebo gel.
MATERIAL AND METHODS
The
protocol for this research study and the subject informed consent
(IFC) were submitted to the human subject committee at UCLA. Study
was commenced, after the IRB approval was obtained. (Attached is
a copy of approved informed consent form.)
A total of 50 subjects, each with a minimum rating of A3 on the
Vita® shade guide and were enrolled for this double-blinded, parallel,
two-cell, randomized clinical trial. The study permitted enrolling
a sufficient number of subjects (25) in each of the two groups to
enable a minimum of 20 subjects in each group to complete the study.
After the initial screening, the subjects (25 each) were assigned
to one of the two groups of the study. In Group one, 25 subjects
will be using NITE WHITE with ACP® regimen as directed by the manufacturers
for minimum of 5 hours every night for 2 weeks. In Group two, 25
subjects will use the placebo regimen 5 hours every night for two
weeks. There are also 2 follow-up examinations of all patients at
approximately three months and six months after the baseline visit.
The patients were accepted based on the following criteria:
Inclusion Criteria
 | Age range between 18 and 65
| Availability of the subject in the area
for nine to twelve months
| Minimum of 20 natural teeth including
at least 4 molars (excluding third molars)
| Subject must be in good general health
| Subjects need to be clinically diagnosed
as not having generalized gingivitis or periodontitis
| At the screening examination, subjects
must complete a questionnaire to ensure qualification for participation
in the study
| Subjects must agree to not have professional
oral prophylaxis or use anti-microbial mouthwashes during the
study period
| Subjects must have maxillary anterior
enamel shade of at least Vita A-3 shade or darker based on a Vita
shade guide arranged in order of value
| Willingness to avoid tobacco, coffee,
dark cola, and red wine during the period of the clinical investigation.
| | | | | | | | |
Exclusion Criteria
| Systemic medications or disease
| Serious oral pathology (e.g. extensive
dental caries, peridontal disease)
| Pregnant or lactating women
| Prophylactic antibiotic coverage for routine
dental therapy
| Orthodontic devices or appliances
| Antibiotic drug therapy
| Crowns on maxillary anterior teeth
| Previous bleaching treatment
| Gingival inflammation
| Participation in other clinical or investigational
trials
| Extreme tetracycline stains or any stain
know to be of tetracycline origin
| | | | | | | | | | |
A
stratified, blocked randomization approach were used to assign subjects
the whitening agent in which the stratification factors will be age,
gender, and oral status.
The product usage was a minimum of 5-6 hours during the night for
a period of 14 days. Each subject were assigned a coded test or placebo
product and instructed on the product usage according to the manufacturer's
directions. Each subject were given a toothpaste (Colgate Tartar Control)
and a soft bristled toothbrush (Colgate Classic) to maintain oral
hygiene.
Subjects were asked to brush and floss twice daily, after breakfast
and before bedtime for at least one minute using their tooth brushing
techniques. Subjects were seen after 7 and 14 days of total treatment
to evaluate enamel shade change gingival index, soft tissue effects,
and concerns of the patient. Shade changes were evaluated using both
Vita shade guide and intra-oral photography. Active bleaching was
discontinued at the end of 14 treatment days. The log was collected
and the patient was told to discontinue the whitening process. Subjects
were seen at 3 and 6 months post-treatment to evaluate their perception
of the Night Guard Vital Bleaching procedure.
At the screening appointment, maxillary alginate impression (Jeltrate
Plusâ ) of the subjects were taken and a stone cast was generated.
A bleaching tray was fabricated from the stone cast using a pressure
molding machine, having a 0.5 mm facial reservoir on teeth #5-12,
and trimmed as described in the manufacturer's instructions. Only
the maxillary arch (teeth # 6, 7, 8, 9, 10, and 11) was evaluated
for bleaching.
A Stratified, blocked randomization approach was used to assign subjects
to the two study groups in which the stratification factors were gender,
age, oral health, and shade of teeth. Each subject received an oral
prophylaxis at least two weeks prior to the beginning of the active
bleaching phase of the study. Subjects were asked to brush and floss
twice daily for one minute. At the baseline appointment, which was
a minimum of two weeks after the oral prophylaxis, the bleaching guard
was delivered and adjusted according to the guidelines provided by
Discus Dental, Inc. A baseline enamel shade for teeth #6, 7, 8, 9
10, and 11 was determined by Vitaâ shade tabs and the results were
recorded. Intra-oral color slides were taken to record enamel shade
with the appropriate Vitaâ shade tab using Yashicaâ Dental-Eye 2 camera,
1:1 magnification with the Kodakâ 64 professional grade color transparency
film. A color corrected light was used to take picture slides and
patients were examined in the same location and at the same time of
the day during the period of the study.
Information about the bleaching procedure and written instructions
were given to each subjects as well as a daily diary card to record
perceived enamel changes, tooth sensitivity irritation, and other
comments regarding the study.
Subjects were examined at baseline, Day 1, Day 7, and Day 14 during
the active phase of the study to evaluate enamel shade change, gingival
index, oral soft tissue, and adverse events. Measurements were also
conducted at 3 month and 6 month follow-up visits.
Subjects were instructed to refrain from routine dental treatments
to the study investigator. Subjects were told that removal from the
study was mandatory if they receive emergency dental treatment that
could influence the plaque growth or if loss of antibiotics or antibacterial
agents during this study were dropped. Any of the above mentioned
scenarios were reported to the study sponsor. Subjects who were excluded
from the analysis.
RESULTS
Two product containers were dispensed to subjects.
The identity of the products was concealed and neither the subjects
nor the investigators had the knowledge of the type of products
dispensed to the subjects. Fifty two subjects were randomized to
placebo or agent. Of these, 47 subjects completed data collection
at 6 months. Since the retention rate of subjects completing the
trial was 90%,only efficacy-analyzable analyses were performed.
No attempt was made to impute the missing data for the five subjects
who were excluded from the analysis.
For the subjects who completed the trial, 24 were randomized to
placebo and 23 to agent. Fifty-three percent were Caucasian and
32% were Asian. Forty-seven percent were female. Sixty-four percent
had no allergies. The average age of the subjects was 34.4 years
(s=10.8yrs) and ranged from 18.5 to 57.1. There was no statistically
significant difference in the mean age of the subjects randomized
to the two groups (p=0.68) or in length of time between dispensing
and return of the product (p=0.43).
For the analysis of shade, descriptive statistics as well as graphs
for the placebo and agent groups are provided for the baseline,
one-week, two-week, three-month, and six-month data collection time
as well as possible changes between successive time points. These
descriptive statistics are given by tooth as well as for the average
of the 6 anterior teeth.
The averaged shade value was analyzed using weighted least squares
approach for a repeated measures analysis of variance (PROC CATMOD,
SAS) which is a more appropriate model than a parametric repeated
measure ANOVA since the shade values are ordinal in nature. This
approach analyzes the mean response functions and partitions the
variation in shade scores among the possible sources of time (baseline,
two weeks, and 6 months), treatment group (placebo and active agent),
and time by treatment interaction (the pattern of change over time
for the two bleaching groups). Contrast within treatments over time
and between treatments at baseline, two weeks, and six months were
performed within the general linear model using the design matrix
from the repeated measures procedure.
There was significant interaction between time and treatment indicating
that the change in averaged shade score from baseline to two weeks
to six months was not the same in the placebo and active agent groups
(p=0.0000). In the placebo group, the averaged shade scores did
change significantly over time (p=0.0002). From baseline two weeks,
the averaged shade change in the placebo group was statistically
significant (p=0.0001) with the mean shade change being 1.7 units.
The change from two weeks to 6 months was not statistically different
(p=0.25).
For the active agent group, the averaged shade scores also changed
significantly over time (p=0.0000). In the active agent group, the
baseline averaged shade scores were significantly different from
the two-week and 6-month scores (p=0.0000 and 0.0000, respectively),
but the two-week scores were not significantly different from the
6-months scores (p=0.11). The active group mean decreased from a
baseline shade unit of 11.4 to 5.1 at 6 months 4.6 at two weeks
see (Table 1) and from a baseline shade unit of 11.4 to 5.1 at 6
months (see Table 2). On average, the placebo and active agent groups
did not differ at baseline in averaged shade scores (p=0.77). The
two groups did differ significantly at two weeks (p=0.0000) and
at six months (p=0.0000).
In terms of the ADA criteria of maintenance of a 2 shade unit decrease,
the two groups also were significantly different in the proportion
of subjects who showed at least a 2 shade unit change. Shade unit
is also defined as shade value. By two weeks, 12 subjects (50%)
of the placebo group had a minimum of a 2 shade unit change (p<0.0001).
All 23 subjects in the active group had a minimum of a s shade unit
change (p<0.0001). At six months, only 7 subjects (29%) of the placebo
group had maintained the two unit decrease while 22 subjects (96%)
of the active group had a minimum two unit decrease in shade (p<0.0001).
For the measurements of sensitivity, vitality, plaque index, gingival
index, and attached gingival, descriptive statistics as well as
graphs are provided for all baseline, one week, two week, three
month, and six month data as well as the changes at occurred in
each of these measures over time. The Savage test, a non-parametric
test, analyzes Savage scores which are the expected order statistics
for the exponential distribution. This test was chosen for the comparison
of the placebo and agent groups at baseline, two weeks, six months
for these measurements since the data tended to cluster at a single
score with only a small percentage of subjects with scores in between
the minimum and the maximum. This distribution of values closely
approximates an exponential distribution.
There were no statistically significant differences between the
placebo and active agent groups at baseline for any measure. At
two weeks, the sensitivity and plaque scores of the two groups were
significantly different (p=0.03 and p=0.009, respectively). None
of the other scores differed at two weeks. Although statistically
different, the median difference between the two groups at two weeks
for plaque was only 0.11 units and the median changes scores from
baseline to two weeks were identical for the two groups. For sensitivity,
the median two-week values were identical, but the active group
had more patients who were experiencing sensitivity on at least
one tooth at two weeks. There was no statistically significant difference
between the placebo group and agent group at six months for any
measure.
Table 1. Comparison of median Baseline
2 Week Shade Differences of Teeth # 6, 7, 8, 9, 10,
and 11 for the placebo group (n=24) and the active group (n=23).
| Teeth
# |
Placebo
Group |
Active
Group |
| 6 |
0.0 |
7.0 |
| 7 |
0.0 |
7.0 |
| 8 |
1.0 |
7.0 |
| 9 |
0.0 |
7.0 |
| 10 |
0.0 |
7.0 |
| 11 |
0.0 |
7.0 |
Table 2. Comparison of median Baseline
6 Month Shade Differences of Teeth # 6, 7, 8, 9, 10,
and 11 for the placebo group (n=24) and the active group (n=23).
| Teeth
# |
Placebo
Group |
Active
Group |
| 6 |
0.0 |
7.0 |
| 7 |
0.0 |
7.0 |
| 8 |
0.0 |
7.0 |
| 9 |
0.0 |
7.0 |
| 10 |
0.0 |
7.0 |
| 11 |
0.0 |
7.0 |
DISCUSSION
The purpose of this study was to determine the clinical efficacy
and the duration of teeth whitening effect of Nite-Whiteâ manufactured
by Discus Dental Inc, at 6 months post-treatment. Each tooth (tooth
#6-11) in the active group displayed a significant decrease in shade
units from baseline t 2-week and from baseline t 6-month. (Tables
1,2). In addition, there was no significant difference between the
2-week shade and the 6 month shade. (Table 1,2) Thus, effect of
teeth-whitening was sustained for at least 6 months after baseline.
Since all the teeth showed the same degree of whitening, anatomical
or morphological and canines did not affect the overall whitening
process. At two weeks, the sensitivity and plaque scores of the
two groups were significantly different (p=0.03 and p=0.009, respectively).
None of the other scores differed at two weeks for sensitivity,
the median two-week values were identical, but the active group
had more patients who were experiencing sensitivity on at least
one tooth at two weeks.
Based on our findings regarding gingival index, attached gingival,
soft tissue evaluation, sensitivity, and pulpal vitality, there
appears to be significant concern for patient safety, as no statistically
significant differences were observed for these indices at baseline
and two weeks whitening and at baseline and six months post-treatment
(p<0.05).
CONCLUSION
A study of 23 subjects in the active group and 24 subjects in the
placebo group given a carbamide peroxide bleaching gel or placebo
for 14 consecutive nights gave the following results:
1. At the end of 6 months, the teeth in the active group had a statistically
signficantly greater mean shade change than in the placebo group.
2. No significant changes resulting from treatment were found in pulpal
vitality, attached gingival, soft tissue evaluation, or gingival index
measurements.
The active 10% carbamide peroxide whitening agent was effective in
whitening teeth and this effect was sustained for 6 months after treatment.
There were no significant adverse events reported between the active
and the placebo group.
REFERENCES:
1. Ouellet, D., Los, S., Case, H., Healy,
R. double-Blind Whitening Night Guard Study Using Ten Percent Carbamide
Peroxide. Journal of Esthetic Dentistry. 1992; 4(30): 79-83
2. Roseentiel, S.F., Gegauff, A.G., Johnson,
W.M. Randomized Clinical Trial of the Efficacy and Safety of a Home
Bleaching Procedure. Quintessencs International. 1996; 27(6): 413-424
3. Settembrini, L., LoPresti, J., Scherer,
W. Removal of Enamel Surface Stains with At-Home Vital Bleaching.
American Journal of Dentistry. 1995; 8(2): 73-74
4. Guidelines for Acceptance of Peroxide
containing Oral Hygiene Products JADA Vol 125, 1140-1142 August,
1994
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