Tooth whitening clinical trials: A global perspective
Robert W. Gerlach,
dds, mph
Abstract: Tooth whitening has been the
subject of extensive clinical trials research since the
introduction of the first hydrogen-peroxide whitening strips
in 2000. Availability of digital image analysis, an
unambiguous and reproducible method for assessing color
change, has contributed to global clinical research and
product development on whitening strips. The research has
included a series of global randomized controlled trials in
distinct sites and cultures, involving 6-6.5% hydrogen
peroxide whitening strips used for 7-21 days. These studies,
conducted at research hospitals, dental schools, and private
dental practice, demonstrated significant color improvement
with whitening strips relative to baseline and/or various
controls without serious adverse events. This integrated
clinical trials research provides important evidence of
long-term safety and effectiveness of tooth whitening with
6-6.5% hydrogen peroxide whitening strips. (Am J Dent
2007;20:3A-6A).
Clinical significance: Randomized
controlled trials, conducted in diverse populations worldwide,
provide evidence of initial tooth color improvement,
post-treatment color stability, and extended safety for
peroxide-containing whitening strips.
Address: Dr. Robert W. Gerlach, The
Procter & Gamble Company, 8700 Mason-Montgomery Road, Mason,
OH 45040-8006 USA. E-:
gerlach.rw@pg.com
Application of digital imaging in tooth whitening randomized
controlled trials
Paul A. Sagel,
bsche
& Robert W. Gerlach,
dds,
mph
Abstract: Purpose: The development of
novel peroxide-based bleaching systems during the last several
years has prompted the need for robust clinical methods to
evaluate whitening response. Advances in digital camera
technology and image analysis software provided the basis for
an instrumental method to assess tooth color closely following
a technique previously used to quantify plaque on tooth
surfaces. In vitro and in vivo research was
conducted to determine reproducibility of color measurements
using this objective, digital imaging method. Methods:
Each of the 16 tabs in a standard shade guide system was
mounted in a jig, and measurement reproducibility was assessed
in vitro from paired digital images collected over a
2-day period. Separately, clinical measurement reproducibility
was assessed in vivo from paired images of 14 healthy
adult volunteers collected over a 2-day period. From these
digital images, mean L*, a*, and b* color values were derived
for each of the 16 individual shade tabs (in vitro
study), or the facial surfaces of the maxillary six anterior
teeth (in vivo study) of the 14 subjects. For each data
set, variability was determined using ANOVA, and between-visit
color measurement reliability was determined from intra-class
correlation coefficients (ICCs). Results: In the in
vitro study, shade tab yellowness (b*) ranged from
9.0-18.6, lightness (L*) ranged from 63.4-76.2, and redness
(a*) ranged from 0.9-3.6. Overall daily means differed by 0.08
units or less, and intra-class correlations for the image
pairs were 0.998 for L*, 0.996 for a* and 0.998 for b*. In the
in vivo assessment, the 14 volunteers exhibited
considerable range in tooth color. Yellowness (b*) ranged from
13.5-21.3, lightness (L*) ranged from 69.2-78.0, and redness
(a*) ranged from 5.2-8.8. Clinical measurement of mean tooth
color from digital images was highly reproducible across
visits. Intra-class correlations for the image pairs were
0.989 for b*, 0.970 for L* and 0.979 for a*. (Am J Dent
2007;20:7A-14A).
Clinical significance: Digital image
analysis, which demonstrated high in vitro and in
vivo color measurement reproducibility, may be broadly
applied in whitening clinical trials or other applications
requiring instrumental and objective assessment of tooth
color.
Address: Paul A.
Sagel, The Procter & Gamble Company, 8700 Mason-Montgomery
Road, Mason, OH 45040 USA. E-:
sagel.pa@pg.com
Professional whitening strips in a university population
Juan Carlos Hernández Guerrero, dds, msc,
phd,
Maria Dolores Jiménez-Farfán, dds, phd,
Armando Lopez-Salgado, dds, Matthew L. Barker, phd
& Robert W. Gerlach, dds, mph
Abstract: Purpose: To evaluate the
clinical response of a professional whitening strip system
used by a university-based population residing in Mexico City,
Mexico. Methods: A randomized, double-blind,
placebo-controlled study was conducted to evaluate the safety
and efficacy of 6.5% hydrogen peroxide whitening strips used
over a 3-week period. A total of 30 volunteer students and
staff at the National Autonomous University of México (Mexico
City) were randomly assigned to the peroxide or placebo strip
groups. Strips were worn for 30 minutes two times a day for 3
weeks. Efficacy was evaluated using digital image analysis to
assess change in L* a* b* tooth color, while safety was
assessed by oral examination and subject interview. Results:
Relative to placebo, the 6.5% hydrogen peroxide strip group
experienced nearly a 4-unit color improvement (Δb*). Treatment
groups differed significantly (P< 0.0001) with respect to
yellowness (Δb*), lightness (ΔL*) and redness (Δa*). Adjusted
mean (SE) overall color improvement (ΔW*) was -4.76 (0.27) for
the peroxide strips, compared to the near zero, -0.21 (0.28)
for the placebo control. Strip use was well tolerated. Minor,
transient tooth sensitivity occurred more frequently in the
peroxide group, and overall, no subjects modified or
discontinued treatment early because of adverse events. (Am
J Dent 2007;20:15A-18A).
Clinical significance: This double-blind
clinical trial in a university population demonstrated highly
significant and appreciable L*a*b* color improvement for the
professional 6.5% hydrogen peroxide whitening strips after 3
weeks use.
Address:
Dr. Juan Carlos Hernández Guerrero, Universidad Nacional
Autónoma de México, Circuito Institutos Sin Número, Cd.
Universitaria, C.P. 04510, Mexico City, Mexico. E-:
jcarlosh@servidor.unam.mx
Daytime use of a custom bleaching tray or whitening
strips:
Initial and
sustained color improvement
Marco Ferrari,
md, dds, phd,
Maria Crysanti Cagidiaco,
md, dds, phd,
Francesca Monticelli,
dds, phd,
Gerard Kugel,
dmd, ms, phd,
Matthew L. Barker,
phd
& Robert W. Gerlach,
dds, mph
Abstract: Purpose: To compare the
clinical response of 6% hydrogen peroxide whitening strips and
a 10% carbamide peroxide custom tray system under common
daytime usage conditions, in an Italian dental research
center. Methods: Informed consent and baseline
measurements were collected, and 43 healthy adults were
randomly assigned to 6% hydrogen peroxide whitening strips
(Crest Whitestrips) or the 10% carbamide peroxide custom tray
(Opalescence 10%). The maxillary arch was treated twice daily
for 30 minutes at-home. Treatment was discontinued after 2
weeks, and subjects were monitored for an additional 4 weeks.
Efficacy (initial and sustained) was measured objectively from
standard digital images of the maxillary facial tooth surfaces
using the international CIELAB system. Safety was assessed
from interview and examination. Treatments were compared after
2 weeks (end-of-treatment) and 6 weeks (4 weeks
post-treatment) using analysis of covariance methods.
Results: Both groups exhibited color improvement at the
Week 2 end-of-treatment visit. For yellowness, mean (SD) Δb*
at Week 2 was -2.10 (0.70) for the strip group and -1.61
(1.03) for the tray group. For lightness, mean (SD) ΔL* at
Week 2 was 1.25 (0.92) for the strip group and 1.17 (1.19) for
the tray group. Compared to Week 2, the strip group retained
89-92% of the initial ∆b* and ∆L* color improvement at Week 6
(4 weeks post-treatment), while the tray group had 80-90%.
Groups differed significantly (P< 0.05) on end-of-treatment
and post-treatment ∆b*, favoring the strips. Both daytime
treatments were well-tolerated, with minor tooth sensitivity
and oral irritation representing the most common findings. (Am
J Dent 2007;20:19A-22A).
Clinical significance: Daytime use of a
6% hydrogen peroxide strip and a 10% carbamide peroxide tray
both resulted in tooth whitening, with significant reduction
in yellowness favoring the strip system initially after 2
weeks and sustained over a 4-week post-treatment period.
Address: Prof. Dr. Marco Ferrari, The
Research Center for Dentistry, Piazza Attias, 19, 57125
Livorno, Italy. E-:
ferrarimar@unisi.it
Clinical trial of long-term color stability of hydrogen
peroxide strips
and sodium percarbonate
film
Mozhgan Bizhang,
dr
med dent, Mario
Müller, dds,
Jin-Ho Phark,
dds, dr
med dent,
Matthew L. Barker,
phd
& Robert W. Gerlach,
dds, mph
Abstract: Purpose: To compare initial
and sustained clinical response of 6% hydrogen peroxide
whitening strips and a 19% sodium percarbonate film in a
randomized controlled trial. Methods: Informed consent
was obtained, after which 72 subjects were randomized to 6%
hydrogen peroxide whitening strips (Crest Whitestrips), 19%
sodium percarbonate brush-applied gel that dries as a film
(Crest Night Effects), or placebo brush-applied gel without
peroxide. Efficacy (digital imaging) and safety (clinical
examination and interview) were assessed after 2 weeks
treatment, and again at up to eight post-treatment timepoints
over an 18-month post-treatment period. Results: For
∆b* (yellowness), end-of-treatment adjusted means ± standard
errors (SE) were -2.37 ± 0.088 for the strip group, -1.36 ±
0.091 for the film group, and -0.08 ± 0.090 for the placebo
group. For ∆L* (brightness), end-of-treatment adjusted means ±
SE were 2.40 ± 0.121 for the strip group, 1.47 ± 0.125 for the
film group, and 0.06 ± 0.122 for the placebo group. Groups
differed significantly (P< 0.02) at end-of-treatment and
throughout post-treatment. All treatments were well-tolerated,
both peroxide-containing systems exhibited appreciable color
retention throughout the 18-month post-treatment period, and
there were no meaningful, persistent adverse events seen with
long-term follow-up. (Am J Dent 2007;20:23A-27A).
Clinical significance: This randomized
controlled trial provided evidence of initial tooth color
improvement, post-treatment color stability, and extended
safety for two peroxide-containing systems (strip and film)
evaluated over an 18-month period.
Address: Dr. Mozhgan Bizhang, Department
of Operative and Preventive Dentistry and Endodontics,
Heinrich-Heine University, Moorenstr. 5, 40225 Düsseldorf,
Germany. E-:
mozhgan.bizhang@med.uni-duesseldorf.de
Randomized clinical trial comparing whitening strips, paint-on
gel
and negative control
Xiao Xu,
dds,
Lingyi Zhu,
dds,
Yu Tang,
dds, Yi Wang,
dds,
Ken Zhang,
dds, phd,
Sarah Li,
bsn,
Lisa C. Bohman,
ms
& Robert W. Gerlach,
dds, mph
Abstract: Purpose: To evaluate efficacy
and safety of peroxide-containing whitening strips and a
paint-on gel relative to a non-peroxide experimental control.
Methods: After informed consent, 52 healthy adults in
Shanghai, China were randomized to one of three treatment
groups: 6% hydrogen peroxide whitening strips (Crest
Whitestrips), 5.9% hydrogen peroxide paint-on gel (Colgate
Simply White), or water rinse which served as a negative
experimental control. Strip use was twice daily over 7 days,
while the paint-on gel and rinse were used twice daily over 14
days. Efficacy was measured from standard digital images of
the maxillary anterior teeth, and safety was assessed from
interview and intraoral examination. Results: Whitening
strips provided the greatest end-of-treatment reduction in
yellowness (b*),
with adjusted means ± standard errors of -1.72 ± 0.18 for the
strip group, -0.48 ± 0.10 for the paint-on gel group, and 0.13
± 0.09 for the water rinse group. For ∆L* (lightness),
end-of-treatment adjusted means ± standard errors were 1.88 ±
0.21 for the strip group, 0.60 ± 0.15 for the paint-on gel,
and -0.10 ± 0.18 for the negative control. Groups differed
significantly (P< 0.007) with respect to ∆b* and ∆L* at
end-of-treatment, as well as other color parameters. All
treatments were well-tolerated. (Am J Dent
2007;20:28A-31A).
Clinical significance: This clinical
study demonstrated that 7 days use of a 6% hydrogen peroxide
strip-based bleaching system provided superior and meaningful
whitening compared to 14-day use of a 5.9% hydrogen peroxide
paint-on gel.
Address: Dr. Xiao Xu, School of
Medicine, No. 9 People’s Hospital, Shanghai Jiao Tong
University, Shanghai 200011 China. E-:
xuxiao@smmail.cn
Clinical trial of tooth whitening with 6% hydrogen
peroxide whitening strips and two whitening dentifrices
Rafael Yudhira,
dds,
Marleen Peumans,
dds, phd,
Matthew L. Barker,
phd
& Robert W. Gerlach,
dds, mph
Abstract: Purpose:
To compare tooth whitening with 6% hydrogen peroxide whitening
strips and two whitening dentifrices in a 12-week randomized
controlled trial at a Belgian dental school. Methods:
After informed consent, 46 healthy adults were randomly
assigned to one of three strip + dentifrice treatment groups.
Subjects received either 6% hydrogen peroxide whitening strips
(Crest Whitestrips) and an anticavity toothpaste (Crest Cavity
Protection), placebo strips and a sodium fluoride (NaF)
whitening dentifrice (Mentadent Whitening Toothpaste) or
placebo strips and a sodium monofluorophosphate (MFP)
whitening dentifrice (Rembrandt Low Abrasion Whitening
Toothpaste). Strip use (peroxide or placebo) was for 30
minutes, twice daily for 2 weeks, while dentifrice use was at
least twice daily for 12 weeks. Efficacy was measured from
standardized digital images of the maxillary facial tooth
surfaces, while safety was evaluated from oral examination and
interview. Treatments were compared after 2 weeks (strip use)
and 12 weeks (dentifrice use) using analysis of covariance.
Results: All subjects completed the 12-week evaluation.
Adjusting for baseline and age, the peroxide strip group had
-2.45 ∆b*, 2.39 ∆L*, and -0.96 ∆a* at Week 2. Between-group
comparisons demonstrated significant (P< 0.0001) reductions in
yellowness and redness, and increased brightness favoring the
peroxide strip group. The peroxide strip group demonstrated
95%+ color retention (∆b* & ∆L*) at Week 12, differing
significantly (P< 0.0001) versus either of the
continuously used whitening dentifrices. There were no
significant (P> 0.18) differences between the whitening
dentifrice groups at any timepoints. All treatments were
well-tolerated, with minor tooth sensitivity and oral
irritation representing the most common findings. (Am J
Dent 2007;20:32A-36A).
Clinical significance:
Twice daily use of 6% hydrogen peroxide whitening strips
for 14 days resulted in initial and sustained superior
improvement in tooth color compared to either of the whitening
dentifrices used continuously for a 3-month period.
Address: Prof. Rafael Yudhira, The
Catholic University of Leuven, Departement Tandheelkunde,
Mondziekten en Kaakchirurgie, UZ Sint-Rafael, Kapucijnenvoer
7, B-3000 Leuven, Belgium. E-*:
Rafael.Yudhira@med.kuleuven.be
