Low Level Laser Therapy Plus Topical Clonazepam Treatment to Burning Mouth Symdrome

Study Overview
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Brief Summary
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Burning mouth syndrome (BMS) is a condition that affects the oral mucosa; this is seen mainly in postmenopausal women. The intensity of burning and its clinical manifestations may be variable between patients. The etiology of the BMS is unknown, just as it is the therapeutic; hence the latter has not been fully accepted. Therefore, the use of low-level laser therapy (LLLT) and topical clonazepam have been proposed as treatment alternatives. The objective is to assess the effectiveness of the combination of LLLT and topical clonazepam for the reduction of burning symptoms. Three groups will be randomly formed: 1) the first group will received topical clonazepam therapy (half of a 2 mg tablet), patients in this group will be asked to applied it in a mouthwash type for 3 minutes and then spit it out; to the same group, six sessions of LLLT (Biolase 10 ©) will be applied in every second day intervals; 2) the second group, will received the same treatment with clonazepam and laser therapies with similar characteristics to the study group, but the laser will be deactivated; 3) the third group, will receive six sessions of LLLT (Biolase 10 ©) in every second day intervals and placebo tablets with similar characteristics to those of clonazepam. For all groups, both treatments will be received for two weeks. For the assessment of oral burning the visual analog scale (VAS) and the Oral Health Impact Profile-14 (OHIP-14) will be used; with these tools we will measure how oral disorders affect daily life. The measurement scales will be applied at the initial assessment and at day 14th, one month, two months and three months post treatment. The means obtained to assess the effectiveness of the treatment will be compared.

Detailed Description
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The study will be carried out at the oral medicine clinic of the Division of Postgraduate Studies and Research of the Faculty of Dentistry of the National Autonomous University of Mexico, during the period of August 2019 to June 2020. This research was approved by the Ethics and Research Committee of the Faculty of Dentistry - Universidad Nacional Autonoma de Mexico. Inclusion criteria will be all patients with BMS, indistinctively of gender. The sample size will be 10 patients in each group, calculated using PaaS computer program with a power of 90.552% to reject the null hypothesis; based on the literature where an average difference of 4 points was obtained in the visual analogue scale from 8.0 to 4.0 with a standard deviation of 1.5 for the group that used laser and 3.0 for the control group, with a significance level of 0.05, in this calculation a number of 9 participants were obtained and the final group size was calculated adding a loss of 10%. Initially, the patient will be assessed by an oral medicine resident and professor. If abnormalities of the mucosa are observed during the assessment, the patient will undergo blood and microbiological tests or biopsy according to the suspected diagnosis; if a diagnosis of BMS is confirmed, the patient will be invited to be part of the study. Using a computer program, randomized block allocation was performed to guarantee equitable participation in each group. Closed envelopes will be used, each envelope will contain the information of which group each patient belongs to and the measurement tools (questionnaires EVA and OHIP-14) that will be applied at the initial moment, at 14 days, 1 month, 2 months and 3 months post treatment. On an individual basis, all patients included in the study will be explained how to use and apply topical clonazepam or placebo tablets, which the patient must suck for 3 minutes periods, after their meals, trying to pass it through all the oral areas; the treatment must not be swallowed nor be placed exclusively under the tongue; to later spit out the leftovers. The tablets corresponding to the days between each laser application will be delivered and the application maneuvers of topical clonazepam or placebo will be evaluated on the morning of the application of the laser treatment, the corresponding observations will be made if necessary. A form with the instructions will be delivered. Patients will be applied Biolase brand InGaAsp diode laser, wavelength 940 nm, tip 400 um, with applications in 10 sites in the oral cavity [lateral of tongue (2 sites), jugal mucosa, lower lip and floor of the mouth) bilaterally at a distance of 15 mm, 10 seconds per point, 15 joules each poit. If the patient reports other specific places where he perceives burning symptoms, it will be applied at the site and the information will be collected for inclusion in the results. Sham laser group will be applying laser inactive therapy with the same specifications. They will carry out 6 sessions, for the same 2 weeks that the topical treatment will last. This research is in according with the regulations of the general health law regarding health research and is at greater than minimum risk.

Official Title
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Use of Low Intensity Laser Combined With Topical Clonazepam for the Treatment of Burning Mouth Syndrome

Conditions
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Burning Mouth Syndrome

Intervention / Treatment
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* Combination Product: low level laser therapy plus topical clonazepam
* Drug: Sham laser plus topical clonazepam
* Radiation: Active laser plus placebo of topical clonazepam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Burning mouth sensation without oral lesions that could be involved with painful symptoms Symtoms of burning sensation more than 3 months Exclusion Criteria: Patients who are under antineoplastic treatment or with a history of malignant neoplasms of the head and neck Active treatment with benzodiazepines or systemic antidepressants Pregnant women Patients unable to follow the indications for administration of oral topical medications Unstimulated saliva production ≤ 0,1 mililiters/minute Sistemic diseases that can produce burning sensation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: group 1:active laser+topical clonazepam, group 2:inactive laser+topical clonazepam, group 3:active laser+placebo clonazepam
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acitve laser+topical clonazepam<br>Using active laser (six sesions) 980 nm, 14 j , plus topical clonazepam 1 mg, 3 times at day, same 14 days both | Combination Product: low level laser therapy plus topical clonazepam<br>* combination of treatment, low level laser therapy (15 joules, 6 sesions, 14 days) plus topical clonazepam (1 mg,3 times per day, 14 days)<br>|
| Sham Comparator: Sham laser+topical clonazepam<br>Using sham laser (six sesions) plus topical clonazepam 1 mg, 3 times at day, same 14 days both | Drug: Sham laser plus topical clonazepam<br>* Sham laser therapy (0 joules, 6 sesions, 14 days) plus topical clonazepam(1 mg,3 times per day, 14 days)<br>|
| Placebo Comparator: Active laser+placebo of topical clonazepam<br>Using active laser (six sesions) 980 nm, 14 j , plus placebo of topical clonazepam (lactose), 3 times at day, same 14 days both | Radiation: Active laser plus placebo of topical clonazepam<br>* low level laser therapy (15 joules, 6 sesions, 14 days) plus placebo topical clonazepam(lactose,3 times per day, 14 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Burning Sensation | Visual Analogue Scale using scale from 0 (No burning sensation) to 10 (maximum burning sensation) | Change from baseline of Burning sensation using Visual Analogue Scale at 15 days, 1 month, 2 months, 3 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life- Oral Health Impact Profile | Oral Health Impact Profile short form of 14 questions, 7 dimensions. Values from 0 to 56, value of 0 is better quality of life and 56 very poor quality of life | Change from baseline of Quality of life using OHIP-14 at 15 days, 1 month, 2 months, 3 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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low-level laser therapy, topical clonazepam