multi pantothanoic

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Special Issue Article_______________________________________________________________________________________________________________________________________________________________

A randomized clinical study to assess the extrinsic staining profiles of stannous- and triclosan-containing dentifrices

TAO HE, DDS, PHD, JOHN M. DUNAVENT, BS, SUSAN K. FIEDLER, BS & ROBERT A. BAKER, MS

ABSTRACT: Purpose: To evaluate the extrinsic stain profiles of two experimental stannous-containing dentifrice prototypes compared to two marketed control dentifrices. Methods: This was a 5-week, randomized, four-treatment, parallel group, double-blind clinical trial of healthy adults. Following a baseline Lobene Stain Index evaluation, subjects received a prophylaxis limited to the 12 anterior teeth to remove surface stain and calculus. They were randomly assigned based on stain scores to one of the four treatment groups: one of two experimental stannous-containing sodium fluoride dentifrices; a non-staining marketed triclosan dentifrice (Colgate Total); or a 0.454% stannous fluoride dentifrice (Crest Gum Care). Subjects brushed for 1 minute twice daily at home with their assigned dentifrice. Stain examinations were repeated at Week 3 and Week 5 to assess treatment differences. Results: For the 96 subjects completing the study, Lobene stain composite mean scores as well as extent (area) and intensity average scores were significantly lower in the two experimental stannous-containing dentifrice groups and the Colgate Total group when compared to Crest Gum Care (P< 0.0001) at both Weeks 3 and 5. There were no statistically significant differences (P> 0.145) in stain accumulation at either time point between the experimental stannous groups and the Colgate Total group by any Lobene stain measure (composite, extent, intensity). All dentifrices were well-tolerated. (Am J Dent 2010;23 Sp Is B:22B-26B).

CLINICAL SIGNIFICANCE: The two experimental stannous-containing multi-benefit dentifrices were associated with no statistically significantly greater extrinsic stain than a leading marketed non-staining control dentifrice after 5 weeks of twice daily use.

: Dr. Tao He, Procter & Gamble Health Care Research Center, 8700 Mason-Montgomery Road, Mason, OH 45040, USA. E-: [email protected]

Introduction

It is widely recognized that todays youth- and appearance-oriented culture prizes an attractive smile and white teeth, with sales of whitening products rising dra-matically in the past decade.1 Not all consumers are content with a single-benefit toothpaste, however. As multi-functional dentifrices have debuted on store shelves, many patients have become aware of, and are seeking out, these value-laden toothpastes which combine the requisite dental caries pro-tection with anti-gingivitis, plaque control, and potentially other benefits conveniently delivered in one tube.

Stannous-containing dentifrices have been used for years for the control of caries, plaque, gingivitis, and tooth sensi-tivity,2-6 however, stannous has historically been perceived to contribute to undesirable staining with long-term use.7,8 Some patients are reticent to accept higher levels of surface stain as the price to pay for better gum health and cleaner teeth, and compliance may suffer.9 Oral hygiene products with the broadest appeal will thus control extrinsic stains, or at a minimum not promote the formation of surface discoloration.

A novel dentifrice prototype has recently been formulated containing sodium fluoride (1450 ppm F-) and stannous chloride. It uses a polychelation technology to stabilize the stannous-fluoride complex and prevent stain.10 Clinical testing has demonstrated multiple benefits for this dentifrice formulation relative to various controls, as reported separately in this issue.11-13 Of continuing interest was the relative surface stain accumulation profile of this formulation in a randomized and controlled clinical trial when compared with other dentifrices; particularly positive (staining) and negative

(non-staining) controls. Crest Gum Carea is a dentifrice containing 0.454% stabilized stannous fluoride. Numerous published reports have documented its efficacy in reducing gingival bleeding and plaque,14-16 but some subjects developed objectionable stain. Crest Gum Care served as a positive control in this clinical study to evaluate the extrinsic stain profiles of two experi-mental stannous-containing sodium fluoride dentifrice proto-types compared to two marketed control dentifrices over a 5-week period.

Materials and Methods

This randomized and controlled, four-treatment, parallel group, double-blind clinical trial was conducted at The Procter & Gamble Oral Health Sciences Center in Mason, Ohio in late 2007. The study was conducted in accordance with the Institutional Review Board human study approval system. At baseline and Weeks 3 and 5, the stain accumulation potential of two experimental dentifrices and two marketed controls were compared:

1. Experimental dentifrice #1 Prototype for dentifrice marketed as Crest Pro-Health in China and blend-a-med Pro-Expert in parts of Europe, containing sodium fluoride (1450 ppm F-) as the active ingredient and stannous chloride as a key excipient.a

2. Experimental dentifrice #2 containing sodium fluoride (1450 ppm F-) as the active ingredient and stannous chloride as a key excipient (minor variations relative to experimental dentifrice #1)a

3. Negative control: Colgate Totalb 0.243% sodium fluoride/

American Journal of Dentistry, Vol. 23, Sp Is B, September, 2010 Dentifrices and extrinsic staining profiles 23B

Fig. 1. The Lobene Stain Index23 measures the intensity and extent (area) of extrinsic dental stain on the facial and lingual surfaces of the twelve anterior teeth; these surfaces are divided into two regions: the gingival and the body region. Figure reproduced courtesy of the Journal of Contemporary Dental Practice.

0.30% triclosan/2% Gantrez copolymer dentifrice. Clinical trials demonstrate Colgate Totals gingival health and plaque control efficacy,17,18 but data do not suggest a propensity for Total or triclosan to promote extrinsic stain;19,20 it was thus included as a negative control in the clinical study reported herein.

4. Positive control: Crest Gum Care 0.454% stannous fluoride dentifrice - formerly marketed in the United States. The product has been reported to produce minor extrinsic stain.21,22

Qualified subjects were defined as those who were generally healthy and at least 18 years of age, possessing at least six anterior teeth suitable for scoring (without crowns, bridge abutments, veneers or large composite restorations). Subjects could not be enrolled if they required antibiotic premedication prior to dental procedures or had severe periodontitis. In addition, individuals who had received a prophylaxis in the preceding 30 days were excluded. After enrollment and until study completion, subjects were monitored for continuing adherence to the entrance criteria. Participants were prohibited from using any non-assigned oral hygiene products or undergoing elective dentistry (including prophylaxis). Subjects gave their written informed consent at the baseline visit. Existing tooth stain was measured for each participant using the Lobene stain evaluation.23 All clinical study evaluations were performed by a single, experienced dental examiner. The Lobene index measures the intensity and extent of extrinsic dental stain on the facial and lingual surfaces of the 12 anterior teeth (Fig. 1). These surfaces of each anterior tooth are divided into two regions: the gingival and the body region. The gingival region is a crescent-shaped band of the labial surface about 2 mm wide, adjacent to the free margin of the gingiva and extending to the crest of the interdental papillae of the adjacent teeth. The remainder of the labial surface is designated as the body region. The gingival and body regions are scored separately for both intensity and

extent using the criteria noted in Fig. 1. Non-gradable and missing sites are not included in the statistical analyses. The Lobene index has two summary variables: the intensity score (sum of all intensity scores divided by all sites graded) and the extent score (sum of all extent scores divided by all sites graded). Additionally, a composite score is calculated for each subject by averaging the product of the intensity and extent scores.

Following the Lobene stain examinations, subjects received a partial prophylaxis by a registered dental hygienist. The purpose of this prophylaxis limited to each subjects anterior teeth (up to 12) was to remove all supragingival plaque, calculus and surface stain prior to test dentifrice use. Subjects were stratified by baseline mean Lobene stain composite score into two groups: (1) equal to or less than 0.65; and (2) greater than 0.65. Separately within strata, subjects were then randomly assigned in blocks of seven to the Colgate Total, experimental stannous dentifrice #1, experimental stannous dentifrice #2, and Crest Gum Care dentifrice test groups at a ratio of 2:2:2:1. The positive control group was one-half the size of the remaining groups as historical data indicated the reduced base size would be sufficient to statistically separate from the negative control group. Subjects in the same household were assigned to the same treatment group. The random assignment process, as well as the test product distribution procedures, was per-formed in a distinct location not permissible to the clinical examiner and data recorders during assignments and distribution. To further maintain the double-blind nature of the trial, the marketed test dentifrices were over-tubed and/or over-labeled (as applicable) in plain white tubes, and then packaged in identical subject kit boxes.

The randomization sequence was prepared by the Clinical Supplies Logistics Department. Study subjects were enrolled and dispensed product by the Oral Health Science Center staff. Subjects were assigned to a kit box number according to the randomization schedule.

24B He et al

Table 1. Baseline subject demographics. Randomized subjects. ____________________________________________________________________________________________________

Experim Experim Colgate Crest Gum Sn #1 Sn #2 Total Care Total Characteristic n=28 n=28 n=28 n=14 n=98 ____________________________________________________________________________________________________

Mean Age (SD)a 42.0 (8.7) 43.1 (10.5) 41.5 (7.8) 40.6 (7.4) 42.0 (8.8) Age Range 26-58 22-62 25-61 26-51 22-62 Female (n, %)b 15 (54%) 20 (71%) 21 (75%) 10 (71%) 66 (67%) Male (n, %)b 13 (46%) 8 (29%) 7 (25%) 4 (29%) 32 (33%)

Race (n, %)c Asian Indian 0 (0%) 1 (4%) 0 (0%) 0 (0%) 1 (1%) Asian Oriental 1 (4%) 0 (0%) 2 (7%) 1 (7%) 4 (4%) Black 1 (4%) 2 (7%) 0 (0%) 0 (0%) 3 (3%) Caucasian 26 (93%) 24 (86%) 25 (89%) 13 (93%) 88 (90%) Hispanic 0 (0%) 1 (4%) 0 (0%) 0 (0%) 1 (1%) Multi-Racial 0 (0%) 0 (0%) 1 (4%) 0 (0%) 1 (1%) ____________________________________________________________________________________________________

Experim. Sn = experimental stannous-containing dentifrice; SD = standard deviation; n = number. a ANOVA was used to compare between-group mean age (P= 0.833). b,c Fishers Exact test was used to compare between-group gender balance (P= 0.353) and between-group racial balance (P= 0.737).

American Journal of Dentistry, Vol. 23, Sp Is B, September, 2010

Table 2. Lobene stain composite index results. Evaluable subjects (n= 96). ____________________________________________________________________________________________________

Treatment comparison P-values

_________________________________

Baseline Crest mean Adjusted Exp. Exp. Gum (SE)a Mean (SE) Sn #1 Sn #2 Care ____________________________________________________________________________________________________

Week 3 Colgate Total (n=27) 0.56 (0.083) 0.23 (0.080) 0.692 0.470


Table 3. Lobene stain intensity index results. Evaluable subjects (n= 96). ____________________________________________________________________________________________________

Treatment comparison P-values

_________________________________

Baseline Crest mean Adjusted Exp. Exp. Gum (SE)a Mean (SE) Sn #1 Sn #2 Care ____________________________________________________________________________________________________

Week 3 Colgate Total (n=27) 0.45 (0.061) 0.22 (0.076) 0.635 0.637

26B He et al

daily unsupervised use, there was no statistically significant difference in Lobene stain formation following a prophylaxis between the two experimental, stannous-containing denti-frices and Colgate Total after both 3 and 5 weeks of brushing. Use of these three dentifrices did, however, result in signifi-cantly less surface staining compared to brushing with the positive control Crest Gum Care, validating the study design model via the Total versus Gum Care expected staining disparities.29 The outcomes were consistent whether analyzed by Lobene composite, intensity or extent scores. The experimental dentifrices tested in this study incorpo-rated both sodium fluoride (1450 ppm F-) and a stannous source (stannous chloride), the synergistic combination of which, during toothbrushing, produces a bioavailable stannous-fluoride complex which would appear to provide similar wide-ranging oral health benefits as previous stannous dentifrices, as reported throughout this issue. The formula uses polychelation technology to prevent stain and stabilize the stannous-fluoride complex, yielding a stain prevention effect comparable to that seen with the non-staining negative control. The significance of this is substantial, given that this novel stannous technology shows a wide range of benefits within a single dentifrice: protection against hypersensitivity, malodor, plaque, tartar, caries, and gingivitis; all without undo extrinsic staining.10 This will give patients seeking an all-inclusive dentifrice who have previously shied away from stannous products an attractive stannous dentifrice that meets a broad range of therapeutic and cosmetic needs, without sacrificing whiter teeth.

a. Procter & Gamble, Cincinnati, OH, USA. b. Colgate-Palmolive Company, New York, NY, USA.

Acknowledgement: To Shelly Campbell for writing assistance.

Disclosure statement: All authors are employees of The Procter & Gamble Company. The study was supported by The Procter & Gamble Company.

Dr. He is a Principal Clinical Scientist, Mr. Dunavent is a Principal Researcher, Ms. Fiedler is a Manager in the Oral Care Clinical Department, and Mr. Baker is a Section Head in Biostatistics at The Procter & Gamble Company Health Care Research Center, Mason, OH, USA.

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