The Efficacy of an Occluding Dentifrice in Providing Relief From Dentinal Hypersensitivity (DH)

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02924350
• Collaborator: (none)
• Enrollment: 205
• Location: 1
• Arms: 2
• Actual Duration (Months): 4.3
• Patients Per Site Per Month: 48

Study Details

Study Description

Brief Summary

This single center study will investigate the efficacy of an experimental stannous fluoride containing dentifrice in relieving DH compared with a standard fluoride dentifrice after short term use.

Condition or Disease	Intervention/Treatment	Phase
Dentin Sensitivity	Other: Stannous fluoride; Other: Sodium monofluorophosphate	N/A

Detailed Description

This was a single centre, 3 day, randomised, examiner blind, two treatment arm, parallel design, stratified (by maximum baseline Schiff sensitivity score of the two selected test teeth), controlled study in participants with at least two sensitive teeth that met the study criteria at the Screening and Baseline visits. Study participants were in good general health, with pre-existing self-reported and clinically diagnosed tooth sensitivity at screening. Participants were assessed at Baseline (pre-treatment), immediately after first treatment, and after 3 days twice daily treatment, to monitor clinical efficacy and safety. At the Screening visit, participants gave their written informed consent to participate in the study. Demography, medical history and concomitant medications were recorded, followed by an oral examination which included an oral soft tissue (OST) examination and assessments to determine eligible teeth. Eligible participants were supplied with a regular fluoride dentifrice (containing 1450 parts per million (ppm) fluoride as sodium monofluorophosphate) to use twice daily (morning and evening) during the acclimatisation period (4-8 weeks) between Screening and Baseline. Each brushing occasion was recorded in a product use diary. First use of the acclimatisation dentifrice was carried out under supervision at the study site. At Baseline (Day 0, pre-treatment), eligibility to continue was assessed. Following an OST examination, tooth sensitivity was assessed (first to a tactile stimulus [Yeaple probe, maximum 20 grams (g) pressure], and then to an evaporative air stimulus [Schiff sensitivity scale]), and the inclusion/exclusion criteria were reviewed. Eligible participants were stratified and randomised to treatment. First use of allocated study treatment was by direct application to the 2 selected test teeth, and was carried out under supervision at the study site. The sensitivity of the 2 test teeth was reassessed immediately post-treatment, first to a tactile stimulus (Yeaple probe, maximum 80g pressure), and then to an evaporative air stimulus (Schiff sensitivity scale). Participants completed a supervised whole mouth brushing with their allocated study treatment prior to leaving the study site. Sensitivity was re-assessed after 3 days twice daily treatment. Each use of study treatment was recorded in a product use diary. Adverse events (AEs) were documented from completion of the first use of acclimatisation dentifrice until 5 days following last administration of study product. Incidents were documented from completion of the first use of investigational product until 5 days following last administration of study product.

Study Design

• Study Type: Interventional
• Actual Enrollment: 205 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Clinical Study Investigating the Efficacy of an Occluding Dentifrice in Providing Relief From Dentinal Hypersensitivity
• Actual Study Start Date: Nov 7, 2016
• Actual Primary Completion Date: Mar 17, 2017
• Actual Study Completion Date: Mar 17, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Test dentifrice containing stannous fluoride All the participants in the test arm applied test dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using test dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).	Other: Stannous fluoride; Supervised direct application (Day 0): Participants applied a pea-sized dose of test dentifrice to each of the 2 qualifying test teeth using their washed and clean finger to gently rub the dentifrice into the tooth's cervical margin for 60 sec. No rinsing was permitted after treatment. Supervised brushing (Day 0, before leaving the site) and Home use (3 days): after dosing a dry toothbrush with a full strip of dentifrice, participants brushed each of the 2 qualifying test teeth first, followed by their whole mouth for at least 60 sec. Participants were permitted to rinse with 5 mL tap water (room temperature) for 5 sec. maximum after brushing on supervised brushing (Day 0) and were also permitted to rinse with tap water after brushing on home use (3 days).
Active Comparator: Control dentifrice containing sodium monofluorophosphate All the participants in the control arm applied control dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using control dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).	Other: Sodium monofluorophosphate; Supervised direct application (Day 0): participants applied a pea-sized dose of control dentifrice to each of the 2 qualifying test teeth using their washed and clean finger to gently rub the dentifrice into the tooth's cervical margin for 60 sec. No rinsing was permitted after treatment. Supervised brushing (Day 0, before leaving the site) and home use (3 days): after dosing a dry toothbrush with a full strip of dentifrice, participants brushed their whole mouth thoroughly for at least 60 sec. Participants were permitted to rinse with 5mL tap water (room temperature) for 5 sec. maximum after brushing in supervised brushing on Day 0 and were also permitted to rinse with tap water after brushing on home use (3 days).

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Schiff Sensitivity Score on Day 3 [Baseline, Day 3]

   The examiner indicated the participant's response to the evaporative air stimulus, after the stimulation of each individual tooth, using the Schiff Sensitivity Scale as follows: 0=Participant does not respond to air stimulation, 1=Participant responds to air stimulus but does not request discontinuation of stimulus, 2=Participant responds to air stimulus and requests discontinuation or moves from stimulus, 3=Participant responds to stimulus, considers stimulus to be painful and requests discontinuation of the stimulus. A reduction in Schiff Sensitivity score indicates improvement in sensitivity.

Secondary Outcome Measures

1. Change From Baseline (Day 0 Pre-treatment) in Schiff Sensitivity Score on Day 0 (After 60 Seconds of Single Direct Application) [At Baseline (Day 0 pre-treatment) and after 60 seconds of single direct application on Day 0]

   The examiner indicated the participant's response to the evaporative air stimulus, after the stimulation of each individual tooth, using the Schiff Sensitivity Scale as follows: 0=Participant does not respond to air stimulation, 1=Participant responds to air stimulus but does not request discontinuation of stimulus, 2=Participant responds to air stimulus and requests discontinuation or moves from stimulus, 3=Participant responds to stimulus, considers stimulus to be painful and requests discontinuation of the stimulus. A reduction in Schiff Sensitivity score indicates improvement in sensitivity.

2. Change From Baseline (Day 0 Pre-treatment) in Tactile Threshold on Day 0 (After 60 Seconds of Single Direct Application) and Day 3 [At Baseline (Day 0 pre-treatment), after 60 seconds of single direct application on Day 0 and Day 3]

   The examiner assessed the response to tactile sensitivity using a Yeaple probe which allowed the application of a known force to the dentin surface, starting at 10gram (g) and raised in increments of 10g until the tactile threshold or maximum force was reached. The tactile threshold for each tooth was determined by asking the participant whether the sensation caused discomfort. The pressure setting at which the participant gave two consecutive 'yes' responses were recorded as the tactile threshold. Higher tactile threshold means less sensitive tooth. At baseline, the maximum force used was 20g; at all subsequent visits, it was 80g.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Consent: Demonstrates understanding of the study procedures, restrictions and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form

• Aged 18-65 years inclusive

• Understands and is willing, able and likely to comply with all study procedures and restrictions

• Good general and mental health with, in the opinion of the investigator or medically qualified designee: a) No clinically significant and relevant abnormalities of medical history or oral examination. b) Absence of any condition that would impact on the participants safety or wellbeing or affect the individual's ability to understand and follow study procedures and requirements

• At Visit 1 (Screening): a) Self-reported history of DH lasting more than six months but not more than 10 years. b) Minimum of 20 natural teeth. c) Minimum of 2 accessible non-adjacent teeth (incisors, canines, pre-molars), preferably in different quadrants, that meet all of the following criteria: -Signs of facial/cervical gingival recession and/or signs of erosion or abrasion (EAR). -Tooth with modified gingival index (MGI) score =0 adjacent to the test area (exposed dentine) only [Lobene, 1986] and a clinical Tooth with signs of sensitivity measured by qualifying evaporative air assessment (Y/N response) mobility of ≤1, -Tooth with signs of sensitivity measured by qualifying evaporative air assessment (Y/N response)

• At Visit 2, Baseline (Pre-treatment):Minimum of two, non-adjacent accessible teeth (incisors, canines, pre-molars), that meet all of the following criteria:-Tooth with signs of sensitivity, measured by qualifying tactile stimulus (Yeaple ≤ 20g) and evaporative air assessment (Schiff sensitivity score ≥ 2)

• Teeth which meet the EAR, MGI and mobility inclusion criteria and none of the dentition exclusion criteria at Screening should be assessed by tactile stimulus at Visit 2. Those teeth which meet the required tactile threshold (Yeaple ≤ 20g) should then be assessed by evaporative air stimulus. When two teeth that meet the study criteria are identified, no further testing is necessary

Exclusion Criteria:

• A woman who is known to be pregnant or who is intending to become pregnant over the duration of the study

• A woman who is breast-feeding

• Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients

• Participation in another clinical study (including cosmetic studies) or receipt of an investigational drug within 30 days of the screening visit

• Previous participation in this study

• Participation in study 205084

• Recent history (within the last year) of alcohol or other substance abuse

• An employee of the sponsor or the study site or members of their immediate family The site for this protocol is the Clinical trials Unit in the Bristol Dental School and Hospital. Employees of the Bristol Dental School and Hospital not associated with the Clinical Trials unit are eligible to participate

• Presence of chronic debilitating disease which, in the opinion of the investigator, could affect study outcomes

• Any condition which, in the opinion of the investigator, causes xerostomia

• Dental prophylaxis within 4 weeks of Screening

• Tongue or lip piercing or presence of dental implants on the selected Test Teeth

• Gross periodontal disease, treatment of periodontal disease (including surgery) within 12 months of Screening, scaling or root planning within 3 months of Screening

• Vital teeth bleaching within 8 weeks of Screening

• Desensitizing treatment within 8 weeks of Screening (professional sensitivity treatments and non-dentifrice sensitivity treatments)

• Tooth with evidence of current or recent caries, or reported treatment of decay within 12 months of Screening

• Tooth 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. Sensitive teeth with contributing aetiologies other than erosion, abrasion or recession of exposed dentine

• Sensitive tooth not expected to respond to treatment with an over-the-counter dentifrice in the opinion of the investigator

• Use of an oral care product indicated for the relief of dentine hypersensitivity within 8 weeks of screening (participants will be required to bring their current oral care products to the site in order to verify the absence of known anti-sensitivity ingredients)

• Daily doses of medication/treatments which, in the opinion of the investigator, could interfere with the perception of pain. Examples of such medications include analgesics, anticonvulsants, antihistamines that cause marked or moderate sedation, sedatives, tranquilisers, anti-depressants, mood-altering and anti-inflammatory drugs

• Currently taking antibiotics or has taken antibiotics within 2 weeks of Baseline

• Daily dose of a medication which, in the opinion of the investigator, is causing xerostomia

• Any participants who, in the judgment of the investigator, should not participate in the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Bristol		United Kingdom	BS1 2LY

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Aug 28, 2016
• Statistical Analysis Plan - Apr 26, 2017

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02924350
• Other Study ID Numbers: 207212
• First Posted: Oct 5, 2016
• Last Update Posted: Aug 20, 2018
• Last Verified: Feb 1, 2018

• Additional relevant MeSH terms: Dentin Sensitivity; Hypersensitivity; Fluorides; Tin Fluorides; Fluorophosphate

Study Results

Participant Flow

Recruitment Details	Participants were recruited at one center in the United Kingdom.
Pre-assignment Detail	A total of 246 participants were screened, out of which 205 participants enrolled in the study. 41 of screened participants were not enrolled because of screening failure. Of 205 enrolled participants, 204 were randomized in study, one participant was not randomized due to lost to follow up.

Arm/Group Title	Test Dentifrice Containing Stannous Fluoride	Control Dentifrice Containing Sodium Monofluorophosphate
Arm/Group Description	All the participants in the test arm applied test dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using test dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).	All the participants in the control arm applied control dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using control dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).
Period Title: Overall Study
STARTED	102	102
COMPLETED	102	100
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Test Dentifrice Containing Stannous Fluoride	Control Dentifrice Containing Sodium Monofluorophosphate	Total
Arm/Group Description	All the participants in the test arm applied test dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using test dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).	All the participants in the control arm applied control dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using control dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).	Total of all reporting groups
Overall Participants	102	102	204
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22.8 (6.61)	22.2 (5.12)	22.5 (5.91)
Sex: Female, Male (Count of Participants)
Female	65 63.7%	74 72.5%	139 68.1%
Male	37 36.3%	28 27.5%	65 31.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	11 10.8%	5 4.9%	16 7.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 4.9%	4 3.9%	9 4.4%
White	85 83.3%	90 88.2%	175 85.8%
More than one race	1 1%	3 2.9%	4 2%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Schiff Sensitivity Score on Day 3
Description	The examiner indicated the participant's response to the evaporative air stimulus, after the stimulation of each individual tooth, using the Schiff Sensitivity Scale as follows: 0=Participant does not respond to air stimulation, 1=Participant responds to air stimulus but does not request discontinuation of stimulus, 2=Participant responds to air stimulus and requests discontinuation or moves from stimulus, 3=Participant responds to stimulus, considers stimulus to be painful and requests discontinuation of the stimulus. A reduction in Schiff Sensitivity score indicates improvement in sensitivity.
Time Frame	Baseline, Day 3

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population, defined as all participants who were randomized, received study treatment at least once & provided at least one post-baseline (post treatment) assessment of efficacy. Number of participants analyzed is from ITT population evaluated at specific time points for each treatment arms respectively.

Arm/Group Title	Test Dentifrice Containing Stannous Fluoride	Control Dentifrice Containing Sodium Monofluorophosphate
Arm/Group Description	All the participants in the test arm applied test dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using test dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).	All the participants in the control arm applied control dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using control dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).
Measure Participants	102	100
Mean (Standard Deviation) [score on a scale]	-1.37 (0.520)	-0.45 (0.443)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test Dentifrice Containing Stannous Fluoride, Control Dentifrice Containing Sodium Monofluorophosphate
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA: change from baseline in Schiff sensitivity score as response and treatment as a factor and baseline Schiff sensitivity score as a covariate
Method of Estimation	Estimation Parameter	Least square (LS) mean difference
	Estimated Value	-0.924
	Confidence Interval	(2-Sided) 95%; -1.0547 to -0.7927
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is first named dentifrice minus second named dentifrice such that a negative difference favors first named dentifrice.

2. Secondary Outcome

Title	Change From Baseline (Day 0 Pre-treatment) in Schiff Sensitivity Score on Day 0 (After 60 Seconds of Single Direct Application)
Description	The examiner indicated the participant's response to the evaporative air stimulus, after the stimulation of each individual tooth, using the Schiff Sensitivity Scale as follows: 0=Participant does not respond to air stimulation, 1=Participant responds to air stimulus but does not request discontinuation of stimulus, 2=Participant responds to air stimulus and requests discontinuation or moves from stimulus, 3=Participant responds to stimulus, considers stimulus to be painful and requests discontinuation of the stimulus. A reduction in Schiff Sensitivity score indicates improvement in sensitivity.
Time Frame	At Baseline (Day 0 pre-treatment) and after 60 seconds of single direct application on Day 0

Outcome Measure Data

Analysis Population Description

ITT population, defined as all participants who were randomized, received study treatment at least once & provided at least one post-baseline(post treatment) assessment of efficacy. Number of participants analyzed is the ITT population evaluated at specific time points for each treatment arms respectively.

Arm/Group Title	Test Dentifrice Containing Stannous Fluoride	Control Dentifrice Containing Sodium Monofluorophosphate
Arm/Group Description	All the participants in the test arm applied test dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using test dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).	All the participants in the control arm applied control dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using control dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).
Measure Participants	102	102
Mean (Standard Deviation) [score on a scale]	-0.63 (0.536)	-0.38 (0.413)

3. Secondary Outcome

Title	Change From Baseline (Day 0 Pre-treatment) in Tactile Threshold on Day 0 (After 60 Seconds of Single Direct Application) and Day 3
Description	The examiner assessed the response to tactile sensitivity using a Yeaple probe which allowed the application of a known force to the dentin surface, starting at 10gram (g) and raised in increments of 10g until the tactile threshold or maximum force was reached. The tactile threshold for each tooth was determined by asking the participant whether the sensation caused discomfort. The pressure setting at which the participant gave two consecutive 'yes' responses were recorded as the tactile threshold. Higher tactile threshold means less sensitive tooth. At baseline, the maximum force used was 20g; at all subsequent visits, it was 80g.
Time Frame	At Baseline (Day 0 pre-treatment), after 60 seconds of single direct application on Day 0 and Day 3

Outcome Measure Data

Analysis Population Description

ITT population, defined as all participants who were randomized, received the study treatment at least once and provided at least one post-baseline (post treatment) assessment of efficacy. Number of participants analyzed is from ITT population evaluated at specific time points for each treatment arms respectively.

Arm/Group Title	Test Dentifrice Containing Stannous Fluoride	Control Dentifrice Containing Sodium Monofluorophosphate
Arm/Group Description	All the participants in the test arm applied test dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using test dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).	All the participants in the control arm applied control dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using control dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).
Measure Participants	102	102
Change from baseline on Day 0	15.10 (14.229)	8.14 (9.823)
Change from baseline on Day 3	32.79 (17.257)	10.45 (11.149)

Adverse Events

Time Frame	up to 64 days (from completion of the first use of acclimatisation dentifrice until 5 days following last administration of study product on Visit 3)
Adverse Event Reporting Description	The time frame for adverse event (AE) reporting was calculated as 64 days including maximum (max.) 56 days of acclimatization period (minimum 28 days and max of 56 days of regular fluoride dentifrice use in acclimatization period, in between of screening and baseline visit), followed by 3 study days and 5 follow up days.
Arm/Group Title	Test Dentifrice Containing Stannous Fluoride		Control Dentifrice Containing Sodium Monofluorophosphate
Arm/Group Description	All the participants in the test arm applied test dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using test dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).		All the participants in the control arm applied control dentifrice on their two test teeth using their finger, followed by brushing these test teeth, followed by brushing the whole mouth using control dentifrice. Participants brushed their teeth for 3 days twice daily (morning /evening).
All Cause Mortality
	Test Dentifrice Containing Stannous Fluoride		Control Dentifrice Containing Sodium Monofluorophosphate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/102 (0%)		0/102 (0%)
Serious Adverse Events
	Test Dentifrice Containing Stannous Fluoride		Control Dentifrice Containing Sodium Monofluorophosphate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/102 (0%)		0/102 (0%)
Other (Not Including Serious) Adverse Events
	Test Dentifrice Containing Stannous Fluoride		Control Dentifrice Containing Sodium Monofluorophosphate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/102 (8.8%)		11/102 (10.8%)
Ear and labyrinth disorders
Ear Pain	1/102 (1%)	1	0/102 (0%)	0
Gastrointestinal disorders
Toothache	1/102 (1%)	1	0/102 (0%)	0
Abdominal pain upper	0/102 (0%)	0	1/102 (1%)	1
Dyspepsia	0/102 (0%)	0	1/102 (1%)	1
Immune system disorders
Seasonal Allergy	1/102 (1%)	1	0/102 (0%)	0
Infections and infestations
Nasopharyngitis	0/102 (0%)	0	2/102 (2%)	2
Musculoskeletal and connective tissue disorders
Pain in extremity	1/102 (1%)	1	0/102 (0%)	0
Neck Pain	0/102 (0%)	0	1/102 (1%)	1
Nervous system disorders
Headache	2/102 (2%)	2	6/102 (5.9%)	6
Dizzines	1/102 (1%)	1	0/102 (0%)	0
Migraine	1/102 (1%)	1	0/102 (0%)	0
Reproductive system and breast disorders
Dysmenorrhoea	1/102 (1%)	1	0/102 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.