| Abstract|| |
Introduction: Recurrent aphthous stomatitis (RAS) is one of the most common ulcerative diseases affecting the general population. The present study aimed to evaluate the clinical efficiency of 0.5% minocycline mouth rinse prescribed along with the topical anesthetic gel and vitamin supplement over the topical anesthetic gel and vitamin supplement prescribed alone for treating RAS. Materials and Methods: A total of 60 participants were randomly divided into two groups—experimental group: 0.5% minocycline mouth rinse prescribed along with vitamin supplement and topical anesthetic gel; and control group: vitamin supplement and topical anesthetic gel alone. The pain symptoms were evaluated using the VAS scores at baseline and first follow-up visits. The data were analyzed using Student's t test. Results: A significant reduction in the pain scores was observed in participants using the 0.5% minocycline mouth rinse prescribed along with vitamin supplement and topical anesthetic gel on the first follow-up visit (P = < 0.001). Conclusion: The 0.5% minocycline mouth rinse prescribed along with vitamin supplement and topical anesthetic gel had shown more reduction in the pain symptoms when compared to topical anesthetic gel and vitamin supplement prescribed alone for the treatment of RAS.
Keywords: Minocycline, mouth rinse, local anesthetic gel, oral ulcers, recurrent aphthous stomatitis, vitamin supplements
|How to cite this article:|
Chugh A, Patnana AK, Kumar P, Chugh VK, Singh S. The clinical efficacy of minocycline mouth rinse on recurrent aphthous stomatitis—A randomized controlled trial. Indian J Dent Res 2022;33:24-9
|How to cite this URL:|
Chugh A, Patnana AK, Kumar P, Chugh VK, Singh S. The clinical efficacy of minocycline mouth rinse on recurrent aphthous stomatitis—A randomized controlled trial. Indian J Dent Res [serial online] 2022 [cited 2022 Nov 27];33:24-9. Available from: https://www.ijdr.in/text.asp?2022/33/1/24/353538
| Introduction|| |
Recurrent aphthous stomatitis (RAS) is a common oral ulcerative condition affecting up to 25% of the general population. RAS usually presents as one of the three clinical variants (minor, major, or herpetiform) of which minor RAS is the most common. RAS minor is associated with relatively small ulcers ranging from 1 to 5 mm which lasts for up to 2 weeks. The etiology of RAS is still considered unknown, but most likely it initiates from a non-infectious inflammatory mucosal disease which is usually associated with immunologic conditions.
Local anesthetic gels and vitamin supplements have been used widely for treating RAS with variable success rates. Topical and systemic corticosteroid therapy is an efficient drug of choice for the management of RAS. However, continuous or inappropriate use of steroids may result in adverse reactions which are mainly related to the systemic absorption of the steroids. A wide variety of drugs and different treatment modalities were tested for their efficacy in managing RAS.,,,
Minocycline which is a semisynthetic tetracycline has antibacterial properties along with some beneficial effects on controlling non-infectious cutaneous diseases as well.,, Minocycline was assumed to have a regulatory effect on cytokines that are related to the development of RAS.,,,, The past literature shows that 0.2% to 0.5% minocycline mouth rinses can be used as an effective treatment option for RAS., However, none of the studies evaluated the efficiency of minocycline mouth rinse over the local anesthetic gel and vitamin supplement for treating RAS. The present study aimed to evaluate the clinical efficiency of 0.5% minocycline mouth rinse prescribed along with the topical anesthetic gel and vitamin supplement over the topical anesthetic gel and vitamin supplement alone for treating RAS.
| Methodology|| |
The present prospective randomized controlled trial was approved by the Institutional Ethical Committee with reference number AIIMS/IEC/2018/541. The present clinical trial was also registered in the Clinical Trial Registry of India (CTRI) with the reference number CTRI/2019/01/017003.
Patients with a significant history of mouth ulcers were screened from the regular dental outpatient department in a medical college and hospital of national importance. The patients diagnosed with recurrent aphthous stomatitis (presence of recurrent and continuous episodes of single or multiple ulcerations) along with the subjective symptoms of pain or burning sensation in the mouth were included in the present trial. The individuals with major aphthous ulcers and herpetiform ulcers, chronic systemic diseases, under chronic steroid therapy, and under medications for psychological diseases were excluded from the present study.
The vitamin supplement (Becosules Z, Pfizer Limited, India) and local anesthetic gel (LOX 2%, NEON, India) with or without 0.5% minocycline (Minoz, Ranbaxy Laboratories Ltd., India) mouth rinse were used to treat the RAS in the present study. A total reduction in the pain or burning sensation in the mouth was considered a successful outcome. No reduction in the pain or burning sensation, any history of allergies, taste alterations, and gastrointestinal disorders were considered as the negative outcomes to the experimental groups.
The sample size was calculated with an absolute precision of 80% and clinically significance level of 0.05, and a sample size of 25 participants per group was calculated. With a dropout rate of about 10%, 30 patients were recruited for each group in the present trial. A computer-generated block random sequence was used to recruit the participants in the present trial. Allocation concealment was performed using the sequentially numbered sealed envelope covers. The random sequence generation and the sealed envelopes preparation were performed by the biostatistician. The principal investigator had screened, enrolled, and assigned the participants to different treatment groups in the present trial. The outcome assessment was conducted by the second and third examiners who were completely unaware of the treatment given to the participant; thus, the outcome assessor was blinded in the present trial.
After getting informed written consent, participants were randomly divided into two groups, consisting of 30 participants in each—experimental group: participants receiving 0.5% minocycline mouth rinse prescribed along with anesthetic gel and vitamin supplement; control group: participants receiving anesthetic gel and vitamin supplement. The pain scores before starting the medications were considered as “baseline data,” and they were recorded by the principal investigator using the visual analog scale (VAS).
The participants in the experimental group were instructed to disperse 100 mg of minocycline tablet in 20 ml of water to make the 0.5% of minocycline mouth rinse. The patients were instructed to rinse with 5 ml of minocycline mouth rinse solution for 5 min four times a day. The patients were instructed to spit the minocycline solution rather than swallowing it after a thorough gargle. The patients were also asked to apply the local anesthetic gel at the site of the ulcer before eating food and vitamin supplement before going to bed. In the control group, the participants were instructed only regarding the use of local anesthetic gel and vitamin supplement similar to the experimental group.
The participants in both groups were asked to fill out the questionnaire regarding the intensity of pain or any side effects (taste alterations, allergic reactions, or digestive tract disturbances) before going to bed every day. Daily pain scores were recorded by the participants using the visual analog scale which ranges from score zero (no pain) to ten (worst possible pain). Patients were strictly instructed to stop filling the VAS scoring sheets and stop using the medications if there is no pain or burning symptoms. Patients were also asked to discontinue the medications if any adverse reactions were observed while using the medications.
The patients with discontinued medications either because of any adverse reactions or remission of symptoms were asked to report to the department immediately, and the patients with partial or no response were recalled after 10 days. The mean of VAS readings when the patients first visited back after treatment was considered as the VAS score of their first follow-up visit. All the included participants in experimental and control groups were recalled after 6 months to evaluate the recurrent episodes of aphthous ulcers after stopping the medications. The patient visit to the department after 6 months of using medications was considered as their second follow-up visit.
The numerical data were expressed as mean ± standard error, and the categorical data were expressed as percentage or proportion. Numerical data were analyzed using Student's t test, and categorical data were analyzed using Chi-square or Fisher's exact test. All the statistical analysis was performed using the SPSS (Version 21) software. The P value of 0.05 was considered statistically significant.
| Results|| |
A total of 120 participants were screened for pain or burning sensation in the mouth out of which 60 participants were excluded and the remaining 60 participants were recruited and randomly allotted to the experimental and control groups [Figure 1]. The screening and recruitment of the participants were performed during the period from November 2018 to February 2019. The recruitment of the participants was stopped once the required number of samples was achieved for the trial. None of the patients were lost for analysis in the first follow-up visit in any of the treatment groups. Four patients in the experimental group and thirteen patients in the control group were lost for analysis in the second follow-up visit.
No statistically significant difference was observed between the distribution of males and females to the experimental and control groups (P = 0.9). In the first follow-up visit, twenty-nine patients in the experimental group and only eight patients in the control group had reported a complete reduction in pain or burning sensation in the mouth and the difference was statistically significant (P = < 0.001). None of the participants had reported any increased ulcerations, side effects, allergies, and gastrointestinal problems from any of the groups in the present trial [Table 1].
|Table 1: Correlation of different parameters between two treatment groups|
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The mean ± standard deviation values for pain score from visual analog scale (VAS) in the experimental group participants at the baseline and first follow-up visit were 7.4 ± 0.94 and 2.7 ± 1.24, respectively. The mean ± standard deviation pain scores in the control group participants at the baseline and first follow-up visits were 7.6 ± 0.63 and 5.9 ± 0.94, respectively. The reduction in pain symptoms in the first follow-up visit showed a significant difference when compared to the baseline data (P = < 0.001) in both experimental and control group participants [Table 2].
|Table 2: Comparison of VAS scores at baseline and on the first follow-up visit in the experimental group and control group|
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The VAS pain scores before starting the intervention were compared to check the baseline equality, and no statistically significant difference was observed between the groups (P = 0.26). As the baseline pain scores before using the medications were similar, pain scores were compared between the two groups in the first follow-up visit. The mean pain scores on the first follow-up visit in the experimental and control group participants were 2.7 ± 1.24 and 5.9 ± 0.94, respectively. A statistically significant difference was observed between the two groups for pain assessment on the first visit with a P value of <0.001 [Table 3]. Two patients in the experimental group and seventeen patients in the control group had reported the recurrence of pain or burning symptoms in the second follow-up visit after 6 months [Figure 2].
|Figure 2: Number of individuals with a history of pain or burning sensation at baseline, on first and second follow-up visits|
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|Table 3: Comparison of VAS scores in the experimental and control group at baseline and on the first follow-up visit|
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| Discussion|| |
The participants with recurrent aphthous stomatitis (presence of recurrent and continuous episodes of single or multiple painful ulcerations) were only included in the present study. The patients with aphthous ulcers which were observed for the first time were not included in the present study, as they can be treated with simple local anesthetic gel and vitamin supplement., The patients with white spot lesions in the oral cavity do also experience subjective symptoms similar (burning sensation or pain) to the RAS; thus, a proper history was taken and clinical examination was performed before including in the trial. All participants were also screened for constipation, gastritis, and excessive stress, and they were referred for medical management as supportive therapy.
Unlike the earlier studies, where the minocycline mouth rinse was compared with placebo or different concentrations of minocycline were compared, the minocycline mouth rinse along with the anesthetic gel and vitamin supplement was compared with anesthetic gel and vitamin supplement alone in the present study. The growing concerns over placebo-controlled trials have led to the development of non-placebo-controlled trials in recent times. Concerning the aforementioned modifications in the clinical trials, the control group in the present study was also given the basic treatment of local anesthetic gel and vitamin supplements for the RAS.
It is always important to consider the economic factors for treating any disease, especially for the more common diseases like RAS. Thus, the pricing of minocycline mouth rinse (Minoz, Ranbaxy, India), local anesthetic gel (LOX 2%, NEON, India), and vitamin supplement (Becosules Z, Pfizer Limited, India) was compared in the present study. It was observed that minocycline mouth rinse is eight times costlier than the regular local anesthetic gel and vitamin supplement available in the market. Thus, considering the very high pricing, evaluating the effectiveness of minocycline mouth rinse over the regular local anesthetic gel and vitamin supplement is quite essential. A significant decrease in the pain scores was observed before and after using the minocycline mouth rinse in the present study. The decreased pain scores by minocycline mouth rinse were in accordance with the earlier reports.,, The clinical efficacy of minocycline mouth rinse on the RAS can be attributed to its immunomodulatory action anti-bacterial properties.
Interestingly, a significant decrease in the pain scores was observed in the control group also, where only the local anesthetic gel and vitamin supplement were prescribed. Though there is a reduction in the pain scores, 73% of the participants in the control group have reported that their ulcers were not completely healed and their pain and burning sensation were not completely reduced. The failure of completely reducing the pain symptoms by the vitamin supplements alone was in accordance with the earlier literature, where it reported that clinicians should not recommend the multivitamin supplements as a routine treatment for the RAS.,
In the present study, the baseline pain scores were compared between the experimental and control groups, and no significant difference (P = 0.26) was observed which was an important factor to compare the postoperative pain scores between the experimental and control groups. There was a significant reduction in the pain scores by the experimental group when compared with the control group in the first follow-up visit. The present study results clearly report that the minocycline mouth rinses along with the local anesthetic gel and vitamin supplements can reduce the pain symptoms of RAS when compared with the local anesthetic gel and vitamin supplement alone. It can also be reported that the minocycline mouth rinse will act as an additive to the anesthetic gel and vitamin supplements for treating RAS.
Limitations of the study
The present study was completely based on patient compliance; though thorough instructions were given for an efficient mouth rinsing program, there might be chances that few of the participants might not follow the instructions, which may vary the study results. In the present study, the correlation between psychological conditions or any other gastrointestinal problems of the participants was not considered, which may also limit the generalizability of the present trial results.
Considering the aforementioned limitations, future trials should be planned such that there will be complete monitoring of the mouth rinsing program by the clinicians. Future trials need to be planned such that the psychological condition of all the participants needs to be evaluated before starting the trial. The future trials need to be directed in such a way that the main limitations such as storing of the minocycline mouth rinse and the possible taste alterations with the minocycline get addressed.
| Conclusion|| |
Minocycline mouth rinse (0.5%) prescribed along with local anesthetic gel and vitamin supplement can be used effectively for treating individuals with a chronic history of RAS. The conventional treatment methods for RAS like local anesthetic gel and vitamin supplement alone failed to treat the pain symptoms completely.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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Dr. Arun Kumar Patnana
Department of Dentistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]