This 24-week, non-comparative clinical study was conducted across two sites at a clinical research facility in Cheshire, UK (Clinicaltrials.gov: NCT02752958). The protocol was approved by the South-Central Hampshire B Research Ethics Committee (Reference: 15/SC/0612). The study was conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use and local laws and regulations. Minor amendments were made to the protocol including addition of a second study site to increase participant recruitment.
Participants
Participants were aged 18–55 yrs, in good general health, with a self-reported history of DH between 0.5–10 yrs. At the screening visit, eligible participants had at least 20 natural teeth and at least two accessible, non-adjacent teeth (incisors, canines, or pre-molars) with signs of erosion, abrasion or facial/cervical gingival recession (EAR), a modified gingival index score of 0 adjacent to the test area [26], clinical tooth mobility of ≤1 [27], and a positive response to a qualifying evaporative (air) assessment. At the baseline visit, eligible participants had a minimum of two accessible non-adjacent teeth exhibiting sensitivity, as determined by evaporative (air) assessment (Schiff sensitivity score of ≥2) [5].
Excluding factors included: a chronic debilitating disease that could affect study outcomes; any condition causing dry mouth; tongue/lip piercings; dental implants; treatments that could interfere with pain perception or cause dry mouth or use of antibiotics during the study/within 2 weeks of baseline; pregnancy; breastfeeding; a known/suspected allergy/intolerance to study materials/ingredients; dental prophylaxis or participation in a study or investigational drug use within 4 weeks, desensitizing treatment, tooth bleaching or use of a DH-indicated oral care product within 8 weeks, scaling or root planning within 3 months or gross periodontal disease or treatment of such within 12 months of screening.
Specific dentition exclusions for test teeth included evidence of current/recent caries or treatment of decay within 12 months of screening; exposed dentine with deep, defective, or facial restorations; teeth used as abutments for partial dentures; full crowns or veneers; orthodontic bands; cracked enamel; sensitive teeth with contributing aetiologies other than EAR; or sensitive teeth not expected to respond to treatment with over-the-counter toothpaste.
Clinical procedures
At the screening visit, participants gave written informed consent and their demographic characteristics, medical history and concomitant medications were recorded. Participants underwent oral soft tissue (OST) and oral hard tissue (OHT) examinations and an evaporative (air) sensitivity test to identify clinically eligible teeth.
Participants who met eligibility criteria were supplied with a regular fluoride toothpaste (1450 ppm fluoride as sodium monofluorophosphate; UK Signal® Family Protection, Unilever plc, Leatherhead, UK) and a toothbrush (Aquafresh® Clean Control [Everyday Clean]; GSK Consumer Healthcare, Brentford, UK) to use twice daily during the acclimatization period between screening and baseline visits; first use was carried out under supervision. Treatment adherence was assessed through participant-completed diaries. Participants stopped using their regular oral care products throughout the study and were could not use any products, including home remedies, for treating sensitive teeth. Routine use of dental floss is normally excluded from dentine hypersensitivity clinical studies however in this 24-week clinical trial dental floss was permitted for impacted food removal only. Throughout the study participants could not chew gum and had to delay non-emergency elective dental treatment/prophylaxis. Before the baseline visit and subsequent treatment visits, participants refrained from all oral hygiene procedures and analgesics for ≥8 h, from eating and drinking for ≥4 h, and from excessive alcohol consumption for ≥24 h. Small sips of water were permitted within 4 h (but not 1 h) of each visit.
At the baseline visit, ongoing eligibility was assessed, any adverse events, incidents and medication changes were recorded and acclimatisation toothpaste adherence was evaluated. Participants completed DHEQ Sections 1 and 2 [14] and underwent an LMS training exercise. DHEQ Section 1 Questions (Q)1–6 was to gather information about pre-treatment DH only; results are not presented. Following OST/OHT examinations, sensitivity of all clinically eligible teeth identified was evaluated by an evaporative (air) test. From the teeth that met the qualifying sensitivity assessments, the investigator selected two non-adjacent teeth (‘test teeth’) to be evaluated throughout the study.
To confirm the clinical response to the study toothpaste, and allow benchmarking with previously reported studies, the evaporative (air) sensitivity (Schiff) measure was selected. Yeaple (tactile) measures were not undertaken, maximising participants focus on self-assessment responses. Evaporative (air) sensitivity was assessed by directing a 1 s air blast onto the exposed dentine surface of each test tooth in turn, having first isolated the tooth surface to prevent adjacent teeth or surrounding soft tissue being exposed to the stimulus. The examiner assessed the participant’s observable stimulus response using the 4-point Schiff Sensitivity Scale [5]. In addition, participants also used self-assessment, Label Magnitude Scales (LMS) for dentin hypersensitivity where they rated the intensity, duration, tolerability and descriptive quality of their response to the evaporative (air) stimulus using100 mm LMS [23]. Each LMS is anchored at 0 mm with ‘no pain’ and incorporates perceived magnitude of specific descriptors for pain: Intensity (‘dim’, ‘dull’, ‘sharp’, ‘stabbing’); Duration (‘temporary’, ‘quick’, ‘lingering’, ‘chronic’); Tolerability (‘tolerable’, ‘uncomfortable’, ‘unnerving’, ‘unbearable’); Description (‘twinge’, ‘ache’, ‘throbbing’, ‘shooting’).
Eligible participants were supplied with the test toothpaste: 0.454% w/w SnF2 (1100 ppm fluoride) (Sensodyne® Repair and Protect Daily Repair Toothpaste, GSK Consumer Healthcare, German marketplace product), with packaging overwrapped in white vinyl to mask identity. Participants applied a full ribbon of toothpaste to the provided toothbrush (replaced at Baseline and Week 12) and brushed for 1 min, twice daily, for 24 weeks, recording each brushing in a provided diary.
First test toothpaste use was carried out under site supervision. At subsequent visits (Weeks 4, 8, 12, 16, 20 and 24), usage adherence was examined based on participant diaries and participants undertook supervised toothbrushing. Participants completed Section 1 (Q7–9 only) and Section 2 of the DHEQ, followed by OST/OHT examinations. The sensitivity of the two test teeth was assessed by response to evaporative (air) stimuli (Schiff Sensitivity Scale and LMS). The sensitivity of any other eligible teeth was assessed using the Schiff Sensitivity Scale.
Safety
The safety population included all participants who received at least one study treatment dose. OST abnormalities and adverse events (AEs) were reported from first use of acclimatization toothpaste until 5 d after last test treatment administration, with intensity graded as mild, moderate or severe. Clinical judgement was exercised to assess any treatment/AE occurrence relationship.
Statistical analysis
Approximately 75 eligible participants were allocated to the study to ensure approximately 60 completed. This number, based on a previous DHEQ study (unpublished findings), was expected to have at least 90% power to detect significant changes to Week 24 for each DHEQ variable, with a significance level (alpha) of 0.05 using a two-sided one-sample t-test.
Efficacy analyses were performed on a modified intent-to-treat (mITT) population, defined as all randomised participants who received at least one treatment dose and had at least one post-baseline efficacy assessment. The per protocol (PP) population additionally included all participants with no efficacy-affecting protocol deviation. There were no formal success criteria.
Several DHEQ measures were analysed as separate endpoints: Section 1: Q7, Q8, Q9; Section 2: Total score (Q1–34); individual domains assessing Restrictions (Q1–4), Adaptation (Q5–16), Social Impact (Q17–21), Emotional Impact (Q22–29) and Identity (Q30–34); Global Oral Health rating (Q35) and Effect on Life Overall (Q36–39). Each endpoint was analysed using a mixed effect analysis of variance (ANOVA), with visit and site as fixed effects and participant as a random effect. Adjusted means were computed for each visit. Post-baseline visits were compared with the baseline visit, with difference of effect calculated along with 95% confidence intervals (CIs) and p-values. Visit by site interaction was included as a term and was found significant at the 10% level; therefore, this was included in the model and all model estimates for within and between visits were reported separately for each site and based on results from visit by site interaction. Due to the study’s exploratory nature, no correction for multiple testing was performed.
At each time point, the mean Schiff sensitivity score (two test teeth, all qualifying teeth) and mean LMS scores (test teeth only) as well as change from baseline were calculated. Analysis was performed as above. Assumption of normality and homogeneity of variance in the ANOVA model were investigated and deemed acceptable.