Clinical trial NCT04034849: Effects of Photobiomodulation in Burning Mouth Syndrome
Official title: Effects of Photobiomodulation With Low-Level Laser Therapy in Burning Mouth Syndrome: A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Burning Mouth Syndrome
Keywords: Low-level Laser Therapy
Burning Mouth Syndrome
Photobiomodulation
Visual Analogue Scale
Oral Health Impact Profile
Clinical Trial
Lead sponsor: Universidad Complutense de Madrid
Sponsor class: OTHER
First posted: 2019-07-26
Enrollment: 20
Sex: ALL
Minimum age (years): 31
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized single blind placebo controlled study
Primary purpose: TREATMENT

Brief summary: The main objective of this study is to assess the effects of Photobiomodulation with Low-level Laser Therapy to the pain management in Burning Mouth Syndrome patients, besides assessing their impact on the different aspects of their quality of life, using the necessary questionnaires to evaluate all the outcomes of chronic pain.

Detailed description: Study design A randomized, single blind, clinical trial was performed among patients with Burning Mouth Syndrome who attended the Oral Medicine Specialist Degree Program at the School of Dentistry at Complutense University in Madrid. This study was approved by the Hospital San Carlos Ethics Committee in Madrid (IEC no. 17/311-R_P) according with the principles of the Helsinki Declaration. This clinical study followed the guidelines established by the Consort Statement (http://www.consort-statement.org/).

Participants Adult patients older than 18 years of age who fulfilled the International Classification of Headache Disorders (ICHD-3) diagnostic criteria for BMS were consecutively included in this study. Patients not interested in participate in the study, unable to understand or answer the questionnaires and follow the appointments, patients suffering hiposialia or Sjögren's syndrome, patients who had received head and neck radiotherapy, pregnant women, patients with uncontrolled systemic diseases (diabetes, thyroid diseases, fibromyalgia or anemia) and patients suffering burning mouth symptoms secondary to local factors were excluded. Patients also had to read and sign and informed consent prior to inclusion in the study.

Before beginning the treatment, all patients provided a full medical history and a complete blood test including blood levels of iron, vitamin B12, folic acid, TSH and basal glucose levels. Patients who did not provide the blood tests, did not attend any of the appointments or follow-ups or did not fulfill correctly the questionnaires were removed from the study.

Interventions LLLT was applied in the study group with a Diode Laser Fox (A.R.C. Laser, Italy) using these parameters: a wavelength of 810 nm, a power of 0.6 W, a power density of 1.2 W/cm2, a beam area of 0.08 cm2 and an energy of 6 J with an application time per point of 10 seconds in 56 points (3 in the vestibular mucosa of the 4 quadrants, 6 in each of the two buccal mucosa, 6 in the hard palate, 4 in each lateral of the tongue, 6 in the dorse of the tongue and 4 sublingual points) with a distance between points of 2mm. It was applied, therefore, a dose of 12 J/cm2 in a continuous mode in a total of 10 sessions, 2 sessions per week for 5 weeks. The laser was applied perpendicularly in contact with the mucosa. All patients and the clinician wore the protective eyeglasses provided with the laser device.

For the placebo group the Low-Level Laser Therapy was applied in the same 56 points, 10 seconds per point and the same number of sessions but with the device turned off.

Outcomes Medical reports, medical questionnaires and blood tests (iron, vit B12, folic acid, TSH and basal glucose) were collected before starting the laser application. Pain was assessed using a Visual Analogue Scale (0-10 cm) by the patients before starting each session and at two follow-up sessions, 1 and 4 months after finishing the treatment.

Different questionnaires validated to Spanish were also fulfilled by patients. The questionnaires were the Short Form 36 Health Survey (SF-36) for the general health status, the Oral Health Impact Profile (OHIP-14) for the oral patient's quality of life, the Epworth sleepiness scale, the psychometric test Symptom Check List 90 (SCL 90), the Beck's depression inventory and the McGill Pain Questionnaire. These questionnaires were fulfilled baseline and at the end of the 10 laser sessions and in the 1st and 4th-months follow-ups.

Sample size The sample size was calculated considering the previous study performed by Sikora et al, 2018 applying Low-Level Laser Therapy in similar parameters with a placebo group. We considered that the acceptable improvement in Laser group would be 4 points in VAS for pain. With a p = 0.05, a statistical power of 90% to detect this difference would require 10 subjects in each study group.

Randomization Burning Mouth Syndrome patients were randomly assigned to one of the treatments (Low-Level Laser Therapy or placebo) in a 1:1 ratio using a computer-generated algorithm stratified by using a block sized of 4. The patient's arrival number was his assigned number for the study following a correlative sequence. Group assignation for each number was kept in a sealed envelope that was no opened until the moment of treatment. An investigator not involved in the Low-Level Laser Therapy performed the randomization. The clinician who applied the Low-Level Laser Therapy was not involved in this process.

Blinding All patients were blinded during all the trial. They wore protective glasses and were also advised to close their eyes during treatment. In addition, the laser was programmed not to emit any type of sound alarm. One clinician collected the VAS and the questionnaires fulfilled by the patients and another clinician applied the laser treatment. All patients were warned of not speaking with the laser clinician. Blinding was revealed after all participants finished the trial, and all the data were analyzed

Statistical methods All the analysis was done using SPSS version 25.0 (SPSS Inc. New York, NY, USA). Statistical analysis included basic descriptive statistics. Comparison of categorical variables was done using chi-square or Fisher's exact test and comparison of continuous variables between test and placebo groups was done using Mann-Whitney U test. Wilcoxon signed-rank test was used to determine whether the intragroup decreases in the different questionnaires were statistically significant. Differences were considered significant if p was less than 0.05.

Eligibility criteria: Inclusion Criteria:

* Adult patients older than 18 years of age who fulfilled the International Classification of Headache Disorders (ICHD-3) diagnostic criteria for Burning Mouth Syndrome Exclusion Criteria
* Patients not interested in participate in the study, unable to understand or answer the questionnaires and follow the appointments, patients suffering hiposialia or Sjögren's syndrome, patients who had received head and neck radiotherapy, pregnant women, patients with uncontrolled systemic diseases (diabetes, thyroid diseases, fibromyalgia or anemia) and patients suffering burning mouth symptoms secondary to local factors

Primary outcomes:
measure: Changes in Visual Analogue Scale for Pain
timeFrame: Baseline (day 1), Session2 (day 4), Session 3 (day 8), Session 4 (day 11), Session 5 (day 15), Session 6 (day 18), Session 7 (day 22), Session 8 (day 25), Session 9 (day 29), Session 10 (day 32), 1st month follow-up (day 60), 4th month follow-up(day 150)
Secondary outcomes:
measure: Description of Pain: Mc Gill Pain Questionnaire validated to Spanish
timeFrame: Baseline (day 1), Session 10 (day 32), 1st month follow-up (day 60), 4th month follow-up (day 150)
measure: General Health Short Form with the 36 Health Survery validated to Spanish
timeFrame: Baseline (day 1), Session 10 (day 32), 1st month follow-up (day 60), 4th month follow-up (day 150)
measure: Oral patient's quality of life with the Oral Health Impact Profile 14 validated to Spanish
timeFrame: Baseline (day 1), Session 10 (day 32), 1st month follow-up (day 60), 4th month follow-up (day 150)
measure: Epworth sleepiness scale validated to Spanish
timeFrame: Baseline (day 1), Session 10 (day 32), 1st month follow-up (day 60), 4th month follow-up (day 150)
measure: Psychometris test Symptom Check List 90 validated to Spanish
timeFrame: Baseline (day 1), Session 10 (day 32), 1st month follow-up (day 60), 4th month follow-up (day 150)
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Universidad Complutense de Madrid
Study officials:
affiliation: Universidad Complutense Madrid
name: Rosa María López-Pintor, PhD
role: STUDY_DIRECTOR
References:
citation: Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.
citation: Montero-Martin J, Bravo-Perez M, Albaladejo-Martinez A, Hernandez-Martin LA, Rosel-Gallardo EM. Validation the Oral Health Impact Profile (OHIP-14sp) for adults in Spain. Med Oral Patol Oral Cir Bucal. 2009 Jan 1;14(1):E44-50.