Comparative Effects of 1.5% Oxalate Strips Versus 5% Potassium Nitrate Dentifrice on Dentin Hypersensitivity

Pejmon Amini, DDS; Melanie Miner, BS, BA; Paul A. Sagel, BSChE; and Robert W. Gerlach, DDS, MPH

A randomized controlled trial was conducted to evaluate the safety and efficacy of a novel 1.5% oxalate sensitivity strip. Healthy adults with dentin hypersensitivity after a cool-air challenge were randomly assigned either three sensitivity strips (Crest® Sensi-Stop™ Strips, Procter & Gamble) plus regular toothpaste (experimental group) or 5% potassium nitrate dentifrice for twice-daily use (control group). First use was supervised, and response was measured immediately after first treatment and again 30 days later after direct provocation with air and tactile stimuli. A total of 79 subjects (mean age 37 years) were randomized and treated. After the first treatment, only the 1.5% oxalate strip group exhibited significant (P < .0001) immediate sensitivity relief to both air and tactile stimulation. Repeated use improved response and, over 30 days, both treatments were effective. Between-group comparisons favored the episodic strips versus the daily-use dentifrice, with a majority of oxalate strip users having no measured air sensitivity at Day 30. Both treatments were well tolerated. A randomized clinical trial showed immediate and durable sensitivity relief for 1.5% oxalate strips and superior response when compared head-to-head versus a potassium nitrate dentifrice.

Dentin hypersensitivity is typically experienced as an exaggerated painful response elicited from one or more teeth after a normal stimulus.1 Prevalence is common, affecting more than 10% of dentate adults in one US practice-based survey.² Individuals typically present with clinical evidence of exposed tooth dentin associated with periodontal diseases, oral hygiene practices, erosion, or other factors, plus open dentin tubules. The mechanism is primarily attributed to stimulus-driven fluid movement within these open dentin tubules (the so-called “hydrodynamic theory”), which activates interdentin receptors.³ The resulting pain response from behaviors as routine as daily oral hygiene or eating/drinking can be varied and profound and may be sufficiently intense to impact on specific quality-of-life assessments.⁴

Dozens of treatment options have been identified.⁵ Of these, the most common approach involves at-home use of dentifrices containing potassium nitrate, which cause local nerve desensitization. In clinical trials, twice-daily use of 5% potassium nitrate in a fluoride-containing dentifrice has been reported to reduce existing sensitivity with a few weeks of regular use.⁶ Other in-office or at-home approaches use topical applications of occluding or precipitating agents episodically to treat exposed dentin.⁷ One such agent, oxalate (a naturally occurring substance from vegetables), has a history of use in dental care for the treatment of dentin hypersensitivity dating from the 1970s. When applied topically, oxalates contribute to the deposition of oxalate-based crystals in dentin tubules, restricting the dentin fluid flow associated with stimuli, thereby relieving dentin hypersensitivity. The mechanism has been demonstrated in laboratory research using fluid dynamics and microscopy, while clinical research has identified a specific role for topical oxalate application in reducing established dentin hypersensitivity.^8-11

Various delivery approaches have been marketed for the treatment of dentin hypersensitivity, including the introduction of liquids and gels that contain oxalates at varying pH levels.^12,13 Recently, a novel oxalate-based device leveraging the ease-of-use found with whitening strips was developed.¹⁴ This new option uses a low total amount of oxalate gel delivered continuously over a short 10-minute period to occlude dentin tubules and reduce sensitivity. A clinical trial was conducted to evaluate the immediate and durable effects of these novel potassium oxalate strips head-to-head versus the prevailing at-home treatment standard, potassium nitrate toothpaste.

A randomized controlled trial evaluated the safety and effectiveness of a novel 1.5% oxalate gel strip versus an antisensitivity dentifrice. Prior to the research, institutional review and informed consent were obtained to screen for healthy adult volunteers with dentin hypersensitivity. Sites with sensitivity were identified on facial surfaces of anterior or posterior teeth consistent with product labeling instructions for the experimental strips without consideration of alignment or other factors. Eligible subjects were randomly assigned by computer algorithm to one of two desensitizing products, balancing groups for age, gender, and baseline air-sensitivity levels. Subjects received either potassium oxalate gel on flexible polyethylene strips (the experimental group) or marketed potassium nitrate dentifrice (the control group). Test products were dispensed in blinded packaging, and all treatments were self-administered. Safety and effectiveness were assessed before and immediately after the first treatment and 30 days thereafter.

The test products were a 1.5% oxalate gel on a 10-mm x 30-mm polyethylene strip (Crest® Sensi-Stop™ Strips, Procter & Gamble, www.dentalcare.com) or a 5% potassium nitrate dentifrice (Sensodyne® Original Flavor, GlaxoSmithKline, www.sensodyne.com). Subjects in the experimental group received a total of three strips plus two tubes of regular anticavity paste (Crest Cavity Protection) and a manual brush (Oral-B® Indicator® soft, Procter & Gamble) for daily oral hygiene, while subjects in the control group received two tubes of antisensitivity/anticavity paste and the same manual brush. For blinding, dentifrices were over-labeled, and all test products were dispensed in blinded, subject-identified kit boxes. In these kit boxes, subjects in the experimental group were dispensed instructions specifying a total of three 10-minute applications of test strips within a 3- to 5-day period, and all subjects received instructions for twice-daily oral hygiene with the assigned brush and paste until study completion. The first use (strip or brushing) in this examiner-blind clinical trial was supervised separately from safety and effectiveness evaluations, and all subsequent usage was at-home and unsupervised.

For each subject, one or two test teeth were identified at baseline, and response was measured at baseline (before treatment), immediately after the first treatment, and 30 days thereafter. Dentin hypersensitivity was assessed using two different provocative challenges: air and tactile. Stimuli were applied directly at test sites and measured clinically blind to treatment assignment immediately after provocation. The tactile challenge was administered first and measured, followed by the air challenge, using standard methods in each case.¹⁵ The stimulus-based tactile challenge (where the stimulus varied) used a calibrated controlled-pressure probe (Yeaple Probe, XiniX Research, Inc., https://yeapleprobe.com) applied directly at test sites using forces ranging from 10 g to 50 g in ascending 10-g intervals until an unfavorable sensitivity response was detected by the clinician. Tactile response was measured at each test site as the minimum grams of force required to elicit a sensitivity response, with non-responsive cases recorded as 50 g. Then, the response-based air challenge (where the response varied) was administered using 1 second of cool air applied directly at test sites using a dental air/water syringe. Air response was measured at each test site clinically using a standard four-point categorical scale (Schiff Index) ranging in severity from unresponsive (0) to responsive/painful/discontinue (3). Safety was assessed from clinical examination. A treatment-blinded examiner conducted all evaluations.

The randomized controlled trial was conducted consistent with pharmaceutical research practices, and analysis used the final locked database inclusive of all valid responses. In this hypothesis-testing study, response to cool air was identified a priori as the primary endpoint. Comparisons to baseline used Wilcoxon Signed Rank Tests, and between-group comparisons used analysis of covariance. All comparisons were two-sided, using 5% levels of significance.

A total of 79 subjects were randomized and had a first supervised use, with 76 evaluable subjects at Day 30. The study population exhibited considerable diversity, with a mean (SD) age of 36.5 (12.03) years, ranging from 18 to 69; 65% of subjects were female. At baseline, mean (SD) for air sensitivity was 2.17 (0.55) using the Schiff Index, while mean (SD) tactile sensitivity was 11.65 (5.65). Groups were balanced (P > .35) on pertinent demographic and sensitivity responses prior to treatment (Table 1), though one subject (in the dentifrice group) started the research with relatively low tactile sensitivity (40 g).

Results demonstrated the relative sensitivity effects of the oxalate strip and the potassium nitrate dentifrice (Figure 1 and Figure 2). Unlike the potassium nitrate group, there was evident improvement in sensitivity response immediately after removal of the 1.5% oxalate strip for both air and tactile challenges. With continued treatment (two additional oxalate strips or daily potassium nitrate brushing), both groups showed improvement in sensitivity, always favoring the experimental group. Day 30 responses were significantly (P < .0001) different from both the pretreatment and immediate posttreatment time points.

Between-group comparisons showed a significant (P < .0001) reduction in air-related sensitivity and a significant (P < .0001) increase in tactile tolerability (reduced sensitivity) after first strip use (Table 2 and Table 3). This represented 23% to 64% greater immediate sensitivity relief with the oxalate strip compared to the dentifrice. After 30 days, the strip group showed 19% to 52% improvements in sensitivity relative to the dentifrice control, with groups differing significantly (P = .0017) on air sensitivity.

Most subjects experienced some sensitivity relief, though onset varied by group. Among the 39 subjects assigned oxalate strips, a majority had an immediate reduction in air sensitivity (51%) and an immediate increase in tactile resistance (54%). In contrast, only 10% to 13% of 40 potassium nitrate subjects had similar measured improvements immediately after first use (Table 4 and Table 5). At Day 30, most subjects had measured improvements in sensitivity. The 95% lower confidence bounds, which represent the most conservative estimates of favorable subject responses, exceeded 78% for the oxalate strips, compared to 70% for the control. At study completion, a majority (57%) of subjects in the oxalate strip group had no measured sensitivity after direct air provocation at sensitive sites (Figure 3). In contrast, approximately one quarter (26%) of potassium nitrate users had no air-related sensitivity after 30 days regular use, with groups differing significantly on complete sensitivity relief (P < .01).

Safety outcomes were unremarkable. Only one subject (in the potassium nitrate dentifrice group) had a treatment-related adverse event (minor gingival irritation), and that event did not contribute to early dropout.

This randomized controlled trial evaluated the immediate and durable effects of 1.5% oxalate strips and potassium nitrate dentifrice on dentin hypersensitivity. The study population was diverse and included adult volunteers with sensitivity at one or more sites ranging from mild to severe. Blinded test products were dispensed for self-application, and responses were measured after two different direct provocations (cool air or controlled pressure probing). Clinical research using an established positive control such as this trial provides important evidence on the absolute and relative effectiveness of 1.5% oxalate strips for existing dentin hypersensitivity and offers key insights on use in patient care.

Foremost, this clinical research establishes the overall safety and effectiveness of 1.5% oxalate strips for the treatment of dentin hypersensitivity. Results from this clinical trial demonstrated a significant and consistent sensitivity improvement with oxalate strips that was evident across subjects, methods, and time points. Some researchers have suggested the use of multiple, different challenges to assess sensitivity and/or establish effectiveness.^16,17 Those opinions may have origins in the complex epidemiology of dentin hypersensitivity, differing mechanisms of action of desensitizing agents, historical norms, or other factors. Irrespective of origin, the use of different methods supports the robustness of the effect, and in this research, 1.5% oxalate strips yielded measureable sensitivity relief for more than 90% of the study population.

Results provide clear evidence of an immediate sensitivity benefit for the 1.5% oxalate strip. Over half of the study subjects experienced an improvement in sensitivity after air or tactile challenges administered directly at test sites immediately after first strip removal. Similar effectiveness was not measured for the dentifrice control, which relies on a different mechanism, one that requires repetitive usage.¹⁸ The immediate sensitivity benefit with oxalate strips is also noteworthy in that strips are a novel device in this area, so none of the subjects in this clinical trial had any prior experience with strip-based treatment of dentin hypersensitivity. In contrast, many of the subjects were likely familiar with strip-based whitening, where strip use is recognized to contribute to some immediate peroxide-associated sensitivity.¹⁹ Despite potential biases from whitening strips, the majority of subjects in this clinical trial had immediate improvement after first treatment, averaging 23% to 64% greater sensitivity relief versus the dentifrice control, and differing significantly from both baseline and control. Unlike potassium nitrate dentifrices, this immediate sensitivity benefit may provide feedback that could impact compliance with this novel treatment.

Such compliance may be a factor in longer-term benefits with oxalate strip use. Crystal deposition and the associated tubular occlusions have been previously identified as a putative desensitizing mechanism.²⁰ Laboratory research has shown repeated use of oxalates further decreased dentin tubular fluid flow after initial treatment.²¹ Results from this clinical trial are consistent with such laboratory findings, as shown via comparisons of the immediate posttreatment (one strip) and Day 30 (three strips) outcomes in the strip group. Other factors, of course, could have contributed to the strip treatment-response observed in this study, and further research would be indicated to directly measure the incremental value of additional strip use. Overall, consistencies between the mechanistic laboratory research and clinical outcomes in this trial provide initial evidence that repeated strip use improves sensitivity relief.

Further, the clinical trial provides important evidence on the durability of oxalate-based sensitivity relief. Depending on randomization, subjects in the clinical trial received one of two sensitivity treatments: three oxalate strips for use over a 3- to 5-day period (the experimental group) or twice-daily use of the assigned dentifrice for 30 days (the positive control). Only the first use was supervised, and all other treatments were at-home and unsupervised. Results were measured immediately after first treatment, and then again after 30 days. With this design, the scheduled Day 30 visit occurred approximately 25 to 27 days after the last planned strip application. Notably, 57% of subjects in the oxalate strip group had complete relief of sensitivity from cool air at Day 30, showing the benefits are sufficiently durable to persist for weeks after last strip treatment.

Potassium nitrate dentifrice, the control in this study, has been reported to yield significant sensitivity relief with repeated application.^22,23 The limited systematic evidence on potassium-containing dentifrices is unclear.²⁴ In this new randomized controlled trial, repeated use of a potassium nitrate dentifrice was shown to significantly reduce sensitivity after 30 days. Onset was delayed, with this clinical trial showing no significant evidence of an immediate response to potassium nitrate. More importantly, the new research provides important evidence of superior sensitivity relief with oxalate strips versus potassium nitrate overall with respect to both the severity and absolute occurrence of dentin hypersensitivity. For severity, strip users had less than half the level of sensitivity (0.46 versus 0.97), while for occurrence, the oxalate strip group had twice as many subjects with no air-related sensitivity (57% versus 26%) compared to the potassium nitrate control. While both products were effective, head-to-head research showed the 1.5% oxalate strips yielded superior relief onset, magnitude of benefit, and complete relief compared to 5% potassium nitrate dentifrice.

A randomized, positively controlled trial evaluated the safety and effectiveness of novel 1.5% oxalate strips on dentin hypersensitivity. The research demonstrated:

• 1.5% oxalate strips are safe and effective, with sensitivity relief evident across multiple methods (direct air and tactile stimulation at sensitive sites).
• Oxalate strip effectiveness was evident immediately after first strip removal.
• Repeated oxalate strip treatment may contribute to significantly reduced sensitivity to the patient.
• Sensitivity benefits were durable, as measured in this study, more than 3 weeks after last strip application.
• Use of the 1.5% oxalate strips resulted in superior sensitivity relief compared to 5% potassium nitrate dentifrice, which is the leading over-the-counter technology.

Theresa Fafard, Bing Reza, and Riann Dondoy provided important contributions to this research.

This research was sponsored by Procter & Gamble.

Pejmon Amini, DDS
Principal Investigator
Silverstone Research Group
Las Vegas, Nevada

Melanie Miner, BS, BA
Statistician
Global Statistics and Data Management
Procter & Gamble
Mason, Ohio

Paul A. Sagel, BSChE
Research Fellow
Global Oral Care R&D
Procter & Gamble
Mason, Ohio

Robert W. Gerlach, DDS, MPH
Research Fellow
Global Oral Care R&D
Procter & Gamble
Mason, Ohio

Figures and Images

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Figure 1

Fig 1. Air-related categorical sensitivity by group and time. (Lower air scores represent decreased sensitivity and P values versus baseline.)

Figure 2

Fig 2. Tactile force (in grams) to elicit sensitivity by group and time. (Higher tactile scores represent decreased sensitivity and P values versus baseline.)

Figure 3

Fig 3. Subjects (%) with complete air-related sensitivity relief at Day 30.

Table 1

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