Exploratory randomised controlled clinical study to evaluate the comparative efficacy of two occluding toothpastes – a 5% calcium sodium phosphosilicate toothpaste and an 8% arginine/calcium carbonate toothpaste – for the longer-term relief of dentine hypersensitivity

Abstract

Objective

To compare the longer-term clinical efficacy of two occlusion-technology toothpastes — a 5% calcium sodium phosphosilicate (CSPS) toothpaste and a commercially available 8% arginine/calcium carbonate toothpaste — in relieving dentine hypersensitivity (DH). Efficacy was also compared with that of a regular fluoride toothpaste control.

Methods

This was an exploratory, randomised, examiner-blind, parallel-group, 11-week, controlled study in healthy adults with self-reported and clinically diagnosed DH. After an acclimatisation period, subjects were randomised to one of three study treatments with which they brushed their teeth twice daily. Sensitivity was assessed at baseline and after 1, 2, 4, 6 and 11 weeks treatment in response to evaporative (air) and tactile stimuli (measured by the Schiff Sensitivity Scale/visual analogue scale and tactile threshold, respectively).

Results

A total of 135 subjects were randomised to treatment. The two occlusion-technology toothpastes performed similarly over the 11-week treatment period. All study treatments showed statistically significant reductions from baseline in DH at all timepoints for all measures ( p < 0.05). Statistically significant and clinically relevant sensitivity relief was observed for both occluding formulations compared with the regular fluoride toothpaste: for evaporative (air) sensitivity within 1 week and for tactile sensitivity at Week 11. No significant differences were detected between the two occluding formulations at any timepoint, for any endpoint. Study treatments were generally well tolerated.

Conclusions

In this exploratory study, a 5% CSPS occluding toothpaste was effective in relieving DH compared with a regular fluoride toothpaste; an 8% arginine/calcium carbonate anti-sensitivity toothpaste provided similar benefits. Improvements in DH continued throughout the 11-week study.

Clinical significance

Dentine hypersensitivity (DH) is a common and painful condition. Twice-daily use of a 5% calcium sodium phosphosilicate toothpaste reduces DH within 1–2 weeks of initiating use. Ongoing, twice daily use of the sensitivity toothpastes evaluated in this study was associated with continued, clinically significant improvements in DH.

Introduction

Gingival recession, or the gradual loss of enamel by tooth wear, can lead to exposed dentine and dentine hypersensitivity (DH) . DH typically presents as a short, sharp pain in response to an external chemical, thermal, tactile or osmotic stimulus that cannot be ascribed to any other dental defect or disease . According to the widely accepted hydrodynamic theory , DH arises when such a stimulus comes into contact with exposed dentine, causing movement of fluid within patent dentinal tubules. This movement is believed to stimulate nerve terminals at the pulpal end of the tubule, resulting in pain .

Based on this hypothesis, there are currently two accepted treatment approaches for DH: (i) direct diffusion of depolarising agents, such as potassium ions, to reduce intra-dental nerve activity ; and (ii) physical blockage of the open dentinal tubules with occluding agents. Agents employed in the latter approach include stannous, strontium or oxalate salts; arginine; silicas and bioactive glasses, all of which act by forming precipitates over the dentine surface and within the tubules, thereby reducing dentinal fluid movement and nerve activation in response to external stimuli .

Calcium sodium phosphosilicate (CSPS) is a particulate bioactive glass incorporated into oral care products for the treatment of DH . Laboratory and clinical in situ studies have shown that CSPS binds preferentially to exposed dentine thereby physically occluding the tubules . On exposure to the aqueous oral environment, CSPS undergoes a series of reactions that promote the formation of a hydroxycarbonate apatite-like layer on the dentine surface and within the tubules . At least thirteen published clinical studies have shown that toothpaste formulations containing CSPS are effective for the treatment of DH , the majority of which used similar longitudinal clinical trial designs .

Toothpastes formulated with 8% arginine (an amino acid) and calcium carbonate (a source of calcium ions) have also been shown to provide relief from the pain of DH in similarly designed clinical studies . In vitro studies report occlusion of dentinal tubules following treatment; the association of arginine and calcium carbonate is described as creating the alkaline conditions that encourage calcium and phosphate ions from saliva to deposit onto dentine .

As recommended by consensus guidelines , the clinical study design for testing dentifrice efficacy in the relief of DH assesses product performance after a period of use, typically after weeks, to allow sufficient time for product effectiveness to become apparent. Since these consensus guidelines were established in 1997, very few DH dentifrice studies that utilise longer treatment periods beyond 8 weeks have been published. For example, a recent systematic review and meta-analysis of clinical studies of desensitizing toothpaste versus placebo included only three studies of 12 weeks duration in its selected data set of 31 studies . The remaining 28 studies were of 8 weeks duration or less. Of the three 12 week studies selected, two were published in the 1990s and one in 2005 and all evaluated dentifrice containing a nerve depolarisation technology, 5% potassium nitrate, not occlusion based dentifrice technologies.

The aim of this program of studies was therefore to evaluate and compare the efficacy of a toothpaste containing 5% CSPS and a commercially available anti-sensitivity toothpaste containing 8% arginine/calcium carbonate bushed twice daily over an extended treatment period and with frequent clinical assessments (1, 2, 4, 6 and 11 weeks).

A regular fluoride toothpaste with no known anti-sensitivity properties was included as a control. To the best of the authors’ knowledge, no studies directly comparing the clinical DH efficacy of these two technologies (when administered as a daily use toothpaste) had been reported in the scientific literature at the time of conducting this study.

This study (Study 1) was exploratory in nature and was not formally powered to detect between-treatment differences, its main purpose being to inform the design of a second, formally powered pivotal study (Study 2, to be reported separately).

Materials and methods

Study design

This was an 11-week, single-centre, randomised, controlled, examiner-blind, three-treatment, parallel-group, exploratory study in healthy adult volunteers with self-reported and clinically diagnosed DH. The study was conducted at the School and Hospital of Stomatology, Wuhan University, Wuhan, PR China. It was approved by the university’s independent ethics committee (IRB number ECB201107) before initiation and conducted in accordance with the Declaration of Helsinki.

Eligible subjects were required to attend the study site on seven occasions: screening, baseline, and 1, 2, 4, 6 and 11 weeks after the baseline visit. At the screening visit, each subject provided written informed consent to participate in the study. Demographic characteristics, medical history and use of concomitant medications were recorded and an oral soft tissue (OST) examination was completed. To determine eligibility, each subject’s dentition was evaluated sequentially for evidence of erosion, abrasion or facial/cervical gingival recession (EAR); gingival health; tooth mobility; and sensitivity to an air-blast stimulus (as indicated by a ‘yes’ response when the subject was questioned about discomfort following stimulation ). Subjects with at least two eligible sensitive teeth were supplied with a regular fluoride toothpaste (Colgate ® Strengthen Fresh containing 1400 ppm fluoride as sodium monofluorophosphate [SMFP]; Colgate-Palmolive [China] Co. Ltd, Guangzhou, China) to use twice daily (morning and evening) for a minimum of 4 weeks between the screening and baseline visits. The purpose of this acclimatisation period was to standardise oral hygiene habits in the study population.

At the baseline visit, subjects were assessed for continuing eligibility. Each was instructed in use of a visual analogue scale (VAS) and asked to complete a VAS training exercise. Following an OST examination, the sensitivity of all clinically eligible teeth identified at the screening visit was evaluated, first by the subject’s response to a tactile stimulus (administered by a constant-pressure force-sensing Yeaple probe ), and then to an evaporative (air) stimulus (assessed by examiner-based Schiff sensitivity score and a subject-completed VAS). There was a minimum of 5 min delay between the end of the tactile assessment and the start of the evaporative (air) assessment to allow the tooth to recover. From those teeth that met a qualifying tactile threshold of ≤20 g and had a Schiff sensitivity score ≥2, the investigator selected two ‘test teeth’ for each eligible subject to be assessed for the remainder of the study.

Eligible subjects were randomly assigned (1:1:1) to receive one of the three study toothpastes: (i) a toothpaste containing 5% (w/w) CSPS and 1450 ppm fluoride as SMFP (an experimental formulation at the time of the study, but later commercially available as Sensodyne ® Repair & Protect, GSKCH); (ii) a commercially available anti-sensitivity toothpaste containing 8% (w/w) arginine, calcium carbonate and 1450 ppm fluoride as SMFP (UK Colgate ® Sensitive Pro-Relief; Colgate-Palmolive Company, Guildford, Surrey, UK) or (iii) a regular fluoride toothpaste containing 1400 ppm fluoride as SMFP (Colgate Triple Protection; Colgate-Palmolive [China] Co. Ltd, Guangzhou, China) as a negative control. Details of all toothpaste ingredients are in Table 1 .

Table 1
List of ingredients for study toothpastes.
5% CSPS Glycerol, polyethylene glycol, silicon dioxide, hydrated silica, CSPS (5%), sodium lauryl sulfate, tegobetain, sodium methyl cocoyl taurate, SMFP (1450 ppm F), titanium dioxide, carbopol, acesulfame potassium, sodium saccharin, flavour
8% arginine/CaCO 3 Arginine (8%), calcium carbonate, aqua, sorbitol, bicarbonate, sodium lauryl sulfate, SMFP (1450 ppm F), aroma, cellulose gum, sodium bicarbonate, tetrasodium pyrophosphate, titanium dioxide, benzyl alcohol, sodium saccharin, xanthan gum, limonene.
Negative control Calcium phosphate, water, sorbitol, hydrated silica, sodium laurel sulfate vinegar, SMFP (1400 ppm F), cellulose gum, aluminium magnesium silicate, essence, saccharin sodium salt, sodium phosphate, sodium ammonium hydrogen phosphate, methylparaben, propyl hydroxybenzoate

Randomisation was stratified, based on the maximum baseline Schiff score (either 2 or 3) of the two selected test teeth. The randomisation schedule was computer generated by the Biostatistics Department of GSKCH; randomisation numbers within each stratum were allocated sequentially by site staff. Individuals who performed the efficacy assessments or who could have influenced the study outcomes were blinded to study treatment. The toothpastes evaluated in this study were completely over-wrapped to mask their identity, but it was not possible to fully blind study treatments. It is rarely possible to ensure identical appearance, taste and packaging for the products evaluated in oral care studies to achieve true double blinding. Maintenance of the blind was confirmed by inspection of product supplies returned by the subjects and by checking that the emergency-use randomisation list with individually masked treatment-allocation details had not been accessed.

Study toothpastes were applied with a manual toothbrush (Crest ® 35 toothbrush; Procter & Gamble, Weybridge, UK). Subjects were instructed to brush with their assigned study toothpaste for 1 min twice daily (morning and evening). To facilitate compliance, the subject’s first brushing was carried out under supervision at the baseline visit. Further supervised brushings were carried out at the end of the 1-, 2-, 4- and 6-week visits. Compliance with toothpaste usage instructions was assessed by review of subject-completed diaries, and visual inspection of the returned toothpaste tubes. Non-compliance issues were evaluated for potential impact on study outcomes on a case-by-case basis.

The sensitivity of the two test teeth selected at baseline was re-assessed in response to evaporative (air) (Schiff sensitivity score and VAS) and tactile (tactile threshold) stimuli after 1, 2, 4, 6 and 11 weeks treatment. Subjects underwent an OST examination at each visit before the clinical assessments of sensitivity.

During the study, subjects were not permitted to use any oral care products other than those provided or any dental products (including home remedies) intended for treating sensitive teeth; they were only permitted to use dental floss for the removal of impacted food. Subjects were requested not to have any non-emergency dental treatment (including prophylaxis) during the course of the study. Subjects were asked to refrain from excessive alcohol consumption for 24 h before each scheduled assessment visit; from all oral hygiene procedures and from chewing gum for at least 8 h; and from eating, drinking and smoking for at least 2 h.

Subjects

Eligible subjects were 18–60 years old, in good general health with no clinically significant and relevant abnormalities of medical history or oral examination. They were required to have a self-reported history of DH lasting more than 6 months but not more than 10 years. At the screening visit, eligible subjects had a minimum of 20 natural teeth, and at least two accessible non-adjacent teeth (incisors, canines or premolars) with: signs of EAR; a gingival index (GI) score ≤1; a clinical mobility score ≤1 and a positive response to a qualifying evaporative (air) assessment of sensitivity. At the baseline visit, subjects were required to have at least two non-adjacent teeth (incisors, canines or premolars) demonstrating signs of sensitivity as determined by qualifying tactile threshold and evaporative (air) assessments.

General exclusion criteria included: pregnancy or breastfeeding; any known or suspected intolerance or hypersensitivity to the study materials or ingredients; participation in another clinical study or receipt of an investigational drug within 30 days, or participation in a desensitising-treatment study within 8 weeks of the screening visit; use of a sensitivity toothpaste within 8 weeks of screening; presence of chronic debilitating disease that could have affected study outcomes; any condition or daily use of medication that was causing xerostomia and daily use of any medication or traditional herbal ingredients or treatments that could have interfered with the perception of pain. General oral exclusions included: dental prophylaxis within 4 weeks of screening; presence of dental implants; tongue or lip piercings; gross periodontal disease or treatment of periodontal disease (including surgery) within the past 12 months; scaling or root planing within 3 months of screening and teeth bleaching within 8 weeks of screening. Specific dentition exclusions at screening included: teeth with current or recent caries, or reported treatment of decay in the past 12 months; teeth with exposed dentine but with deep, defective or facial restorations; teeth used as abutments for fixed or removable partial dentures; teeth with full crowns or veneers, orthodontic bands or cracked enamel and sensitive teeth with contributing aetiologies other than EAR.

Assessments

At screening, gingival health was assessed for teeth with signs of EAR using the 4-point GI . Tooth mobility was assessed for all teeth with a score ≤1, based on a modification to the Miller Index , scored as: 0 = no movement, or mobility of the crown of the tooth <0.2 mm in a horizontal direction; 1 = mobility of the crown of the tooth 0.2–1 mm in a horizontal direction; 2 = mobility of the crown of the tooth >1 mm in a horizontal direction; 3 = mobility of the crown of the tooth in a vertical direction as well.

As recommended by consensus guidelines , two independent stimulus-based efficacy measures were used to assess DH: tactile and evaporative (air) sensitivity. Two examiners performed the clinical assessments; one conducted the evaporative (air) sensitivity evaluation and the other performed the tactile threshold assessment throughout the study.

Tactile sensitivity was assessed using an electronic constant-pressure force-sensing (Yeaple) probe that allowed application of a known force to the dentine surface, starting at 10 g and rising in increments of 10 g. The gram setting that elicited two consecutive “yes” responses from the subject (where “yes” indicated that the stimulus caused pain) was recorded as the tactile threshold (g). At baseline, the maximum force used was 20 g; at all subsequent visits, it was 80 g. The greater the tactile threshold, the less sensitive the tooth. The Yeaple probe was calibrated daily.

Evaporative (air) sensitivity was evaluated after tactile sensitivity (with at least 5 min between assessment types to allow for tooth recovery time). The examiner directed a maximum 1-s air blast from a triple air dental syringe onto the exposed dentine surface of each test tooth in turn, having first isolated the test tooth surface to prevent adjacent teeth or surrounding soft tissue being exposed to the stimulus. The examiner assessed the subject’s observable responses to the stimulus using the 4-point Schiff Sensitivity Scale (on which 0 = subject does not respond to air stimulus; 1 = subject responds to air stimulus but does not request discontinuation; 2 = subject responds to air stimulus and requests discontinuation or moves from stimulus; 3 = subject responds to stimulus, considers stimulus to be painful, and requests discontinuation of the stimulus) . Subjects also rated the intensity of their response to the air stimulus using a 100 mm VAS (from 0 = ‘no pain’ to 100 = ‘worst pain imaginable’).

Safety

Spontaneously-reported adverse events (AEs) and any abnormalities in the OST examination were recorded from the first supervised brushing with the acclimatisation toothpaste at the screening visit until 5 days after the last administration of study product. The investigator assessed the relationship between investigational product and the occurrence of each AE using clinical judgment, and graded the intensity of the AE as mild, moderate or severe. Treatment-emergent AEs were reported for the safety population, which included all randomised subjects who received the study treatment.

Data analysis

This study was not formally powered to detect between-treatment differences. A sufficient number of subjects were screened to randomise a maximum of 135 subjects (approximately 45 to each treatment group), with the aim of approximately 40 subjects per treatment group completing the study. Data were analysed for the intent-to-treat (ITT) population, which comprised all subjects who were randomised, who received at least one study treatment during the study and who provided at least one post-baseline assessment of efficacy. The evaporative (air) sensitivity (Schiff sensitivity and VAS scores) and tactile threshold outcomes were calculated as the subject-level mean change from baseline for the two selected test teeth at 1, 2, 4, 6 and 11 weeks. All significance tests were conducted at the two-sided 5% significance level without adjustment for multiple testing. An analysis of covariance (ANCOVA) model was used for analysis of each efficacy endpoint, with treatment as a fixed effect and baseline value as covariate. For analyses of VAS and tactile-threshold outcomes, the baseline Schiff stratification value was also included in the ANCOVA model as a fixed effect. Data are presented as the adjusted mean subject-level change from baseline (with 95% confidence interval [CI] and p -value) within each treatment group, and the difference in mean subject-level changes between groups (with 95% CI and p -value).

Materials and methods

Study design

This was an 11-week, single-centre, randomised, controlled, examiner-blind, three-treatment, parallel-group, exploratory study in healthy adult volunteers with self-reported and clinically diagnosed DH. The study was conducted at the School and Hospital of Stomatology, Wuhan University, Wuhan, PR China. It was approved by the university’s independent ethics committee (IRB number ECB201107) before initiation and conducted in accordance with the Declaration of Helsinki.

Eligible subjects were required to attend the study site on seven occasions: screening, baseline, and 1, 2, 4, 6 and 11 weeks after the baseline visit. At the screening visit, each subject provided written informed consent to participate in the study. Demographic characteristics, medical history and use of concomitant medications were recorded and an oral soft tissue (OST) examination was completed. To determine eligibility, each subject’s dentition was evaluated sequentially for evidence of erosion, abrasion or facial/cervical gingival recession (EAR); gingival health; tooth mobility; and sensitivity to an air-blast stimulus (as indicated by a ‘yes’ response when the subject was questioned about discomfort following stimulation ). Subjects with at least two eligible sensitive teeth were supplied with a regular fluoride toothpaste (Colgate ® Strengthen Fresh containing 1400 ppm fluoride as sodium monofluorophosphate [SMFP]; Colgate-Palmolive [China] Co. Ltd, Guangzhou, China) to use twice daily (morning and evening) for a minimum of 4 weeks between the screening and baseline visits. The purpose of this acclimatisation period was to standardise oral hygiene habits in the study population.

At the baseline visit, subjects were assessed for continuing eligibility. Each was instructed in use of a visual analogue scale (VAS) and asked to complete a VAS training exercise. Following an OST examination, the sensitivity of all clinically eligible teeth identified at the screening visit was evaluated, first by the subject’s response to a tactile stimulus (administered by a constant-pressure force-sensing Yeaple probe ), and then to an evaporative (air) stimulus (assessed by examiner-based Schiff sensitivity score and a subject-completed VAS). There was a minimum of 5 min delay between the end of the tactile assessment and the start of the evaporative (air) assessment to allow the tooth to recover. From those teeth that met a qualifying tactile threshold of ≤20 g and had a Schiff sensitivity score ≥2, the investigator selected two ‘test teeth’ for each eligible subject to be assessed for the remainder of the study.

Eligible subjects were randomly assigned (1:1:1) to receive one of the three study toothpastes: (i) a toothpaste containing 5% (w/w) CSPS and 1450 ppm fluoride as SMFP (an experimental formulation at the time of the study, but later commercially available as Sensodyne ® Repair & Protect, GSKCH); (ii) a commercially available anti-sensitivity toothpaste containing 8% (w/w) arginine, calcium carbonate and 1450 ppm fluoride as SMFP (UK Colgate ® Sensitive Pro-Relief; Colgate-Palmolive Company, Guildford, Surrey, UK) or (iii) a regular fluoride toothpaste containing 1400 ppm fluoride as SMFP (Colgate Triple Protection; Colgate-Palmolive [China] Co. Ltd, Guangzhou, China) as a negative control. Details of all toothpaste ingredients are in Table 1 .

Table 1
List of ingredients for study toothpastes.
5% CSPS Glycerol, polyethylene glycol, silicon dioxide, hydrated silica, CSPS (5%), sodium lauryl sulfate, tegobetain, sodium methyl cocoyl taurate, SMFP (1450 ppm F), titanium dioxide, carbopol, acesulfame potassium, sodium saccharin, flavour
8% arginine/CaCO 3 Arginine (8%), calcium carbonate, aqua, sorbitol, bicarbonate, sodium lauryl sulfate, SMFP (1450 ppm F), aroma, cellulose gum, sodium bicarbonate, tetrasodium pyrophosphate, titanium dioxide, benzyl alcohol, sodium saccharin, xanthan gum, limonene.
Negative control Calcium phosphate, water, sorbitol, hydrated silica, sodium laurel sulfate vinegar, SMFP (1400 ppm F), cellulose gum, aluminium magnesium silicate, essence, saccharin sodium salt, sodium phosphate, sodium ammonium hydrogen phosphate, methylparaben, propyl hydroxybenzoate

Randomisation was stratified, based on the maximum baseline Schiff score (either 2 or 3) of the two selected test teeth. The randomisation schedule was computer generated by the Biostatistics Department of GSKCH; randomisation numbers within each stratum were allocated sequentially by site staff. Individuals who performed the efficacy assessments or who could have influenced the study outcomes were blinded to study treatment. The toothpastes evaluated in this study were completely over-wrapped to mask their identity, but it was not possible to fully blind study treatments. It is rarely possible to ensure identical appearance, taste and packaging for the products evaluated in oral care studies to achieve true double blinding. Maintenance of the blind was confirmed by inspection of product supplies returned by the subjects and by checking that the emergency-use randomisation list with individually masked treatment-allocation details had not been accessed.

Study toothpastes were applied with a manual toothbrush (Crest ® 35 toothbrush; Procter & Gamble, Weybridge, UK). Subjects were instructed to brush with their assigned study toothpaste for 1 min twice daily (morning and evening). To facilitate compliance, the subject’s first brushing was carried out under supervision at the baseline visit. Further supervised brushings were carried out at the end of the 1-, 2-, 4- and 6-week visits. Compliance with toothpaste usage instructions was assessed by review of subject-completed diaries, and visual inspection of the returned toothpaste tubes. Non-compliance issues were evaluated for potential impact on study outcomes on a case-by-case basis.

The sensitivity of the two test teeth selected at baseline was re-assessed in response to evaporative (air) (Schiff sensitivity score and VAS) and tactile (tactile threshold) stimuli after 1, 2, 4, 6 and 11 weeks treatment. Subjects underwent an OST examination at each visit before the clinical assessments of sensitivity.

During the study, subjects were not permitted to use any oral care products other than those provided or any dental products (including home remedies) intended for treating sensitive teeth; they were only permitted to use dental floss for the removal of impacted food. Subjects were requested not to have any non-emergency dental treatment (including prophylaxis) during the course of the study. Subjects were asked to refrain from excessive alcohol consumption for 24 h before each scheduled assessment visit; from all oral hygiene procedures and from chewing gum for at least 8 h; and from eating, drinking and smoking for at least 2 h.

Subjects

Eligible subjects were 18–60 years old, in good general health with no clinically significant and relevant abnormalities of medical history or oral examination. They were required to have a self-reported history of DH lasting more than 6 months but not more than 10 years. At the screening visit, eligible subjects had a minimum of 20 natural teeth, and at least two accessible non-adjacent teeth (incisors, canines or premolars) with: signs of EAR; a gingival index (GI) score ≤1; a clinical mobility score ≤1 and a positive response to a qualifying evaporative (air) assessment of sensitivity. At the baseline visit, subjects were required to have at least two non-adjacent teeth (incisors, canines or premolars) demonstrating signs of sensitivity as determined by qualifying tactile threshold and evaporative (air) assessments.

General exclusion criteria included: pregnancy or breastfeeding; any known or suspected intolerance or hypersensitivity to the study materials or ingredients; participation in another clinical study or receipt of an investigational drug within 30 days, or participation in a desensitising-treatment study within 8 weeks of the screening visit; use of a sensitivity toothpaste within 8 weeks of screening; presence of chronic debilitating disease that could have affected study outcomes; any condition or daily use of medication that was causing xerostomia and daily use of any medication or traditional herbal ingredients or treatments that could have interfered with the perception of pain. General oral exclusions included: dental prophylaxis within 4 weeks of screening; presence of dental implants; tongue or lip piercings; gross periodontal disease or treatment of periodontal disease (including surgery) within the past 12 months; scaling or root planing within 3 months of screening and teeth bleaching within 8 weeks of screening. Specific dentition exclusions at screening included: teeth with current or recent caries, or reported treatment of decay in the past 12 months; teeth with exposed dentine but with deep, defective or facial restorations; teeth used as abutments for fixed or removable partial dentures; teeth with full crowns or veneers, orthodontic bands or cracked enamel and sensitive teeth with contributing aetiologies other than EAR.

Assessments

At screening, gingival health was assessed for teeth with signs of EAR using the 4-point GI . Tooth mobility was assessed for all teeth with a score ≤1, based on a modification to the Miller Index , scored as: 0 = no movement, or mobility of the crown of the tooth <0.2 mm in a horizontal direction; 1 = mobility of the crown of the tooth 0.2–1 mm in a horizontal direction; 2 = mobility of the crown of the tooth >1 mm in a horizontal direction; 3 = mobility of the crown of the tooth in a vertical direction as well.

As recommended by consensus guidelines , two independent stimulus-based efficacy measures were used to assess DH: tactile and evaporative (air) sensitivity. Two examiners performed the clinical assessments; one conducted the evaporative (air) sensitivity evaluation and the other performed the tactile threshold assessment throughout the study.

Tactile sensitivity was assessed using an electronic constant-pressure force-sensing (Yeaple) probe that allowed application of a known force to the dentine surface, starting at 10 g and rising in increments of 10 g. The gram setting that elicited two consecutive “yes” responses from the subject (where “yes” indicated that the stimulus caused pain) was recorded as the tactile threshold (g). At baseline, the maximum force used was 20 g; at all subsequent visits, it was 80 g. The greater the tactile threshold, the less sensitive the tooth. The Yeaple probe was calibrated daily.

Evaporative (air) sensitivity was evaluated after tactile sensitivity (with at least 5 min between assessment types to allow for tooth recovery time). The examiner directed a maximum 1-s air blast from a triple air dental syringe onto the exposed dentine surface of each test tooth in turn, having first isolated the test tooth surface to prevent adjacent teeth or surrounding soft tissue being exposed to the stimulus. The examiner assessed the subject’s observable responses to the stimulus using the 4-point Schiff Sensitivity Scale (on which 0 = subject does not respond to air stimulus; 1 = subject responds to air stimulus but does not request discontinuation; 2 = subject responds to air stimulus and requests discontinuation or moves from stimulus; 3 = subject responds to stimulus, considers stimulus to be painful, and requests discontinuation of the stimulus) . Subjects also rated the intensity of their response to the air stimulus using a 100 mm VAS (from 0 = ‘no pain’ to 100 = ‘worst pain imaginable’).

Safety

Spontaneously-reported adverse events (AEs) and any abnormalities in the OST examination were recorded from the first supervised brushing with the acclimatisation toothpaste at the screening visit until 5 days after the last administration of study product. The investigator assessed the relationship between investigational product and the occurrence of each AE using clinical judgment, and graded the intensity of the AE as mild, moderate or severe. Treatment-emergent AEs were reported for the safety population, which included all randomised subjects who received the study treatment.

Data analysis

This study was not formally powered to detect between-treatment differences. A sufficient number of subjects were screened to randomise a maximum of 135 subjects (approximately 45 to each treatment group), with the aim of approximately 40 subjects per treatment group completing the study. Data were analysed for the intent-to-treat (ITT) population, which comprised all subjects who were randomised, who received at least one study treatment during the study and who provided at least one post-baseline assessment of efficacy. The evaporative (air) sensitivity (Schiff sensitivity and VAS scores) and tactile threshold outcomes were calculated as the subject-level mean change from baseline for the two selected test teeth at 1, 2, 4, 6 and 11 weeks. All significance tests were conducted at the two-sided 5% significance level without adjustment for multiple testing. An analysis of covariance (ANCOVA) model was used for analysis of each efficacy endpoint, with treatment as a fixed effect and baseline value as covariate. For analyses of VAS and tactile-threshold outcomes, the baseline Schiff stratification value was also included in the ANCOVA model as a fixed effect. Data are presented as the adjusted mean subject-level change from baseline (with 95% confidence interval [CI] and p -value) within each treatment group, and the difference in mean subject-level changes between groups (with 95% CI and p -value).

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Jun 19, 2018 | Posted by in General Dentistry | Comments Off on Exploratory randomised controlled clinical study to evaluate the comparative efficacy of two occluding toothpastes – a 5% calcium sodium phosphosilicate toothpaste and an 8% arginine/calcium carbonate toothpaste – for the longer-term relief of dentine hypersensitivity
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