Low-level Laser Therapy on Inflammatory Mediators During Chemotherapy-induced Oral Mucositis

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to evaluate the effect of low-level laser therapy (LLLT) on the severity of oral mucositis (OM) and inflammatory mediators (pro- and anti-inflammatory cytokines, metalloproteinases and growth factors) levels in saliva and blood; furthermore, analyze the effect of LLLT in product modulation of oxidative stress and cell damage from the oral mucosa transplant patients.

Detailed Description
-----------------
This is a randomized clinical trial in which the proposed analysis will be performed from saliva samples of patients transplanted bone marrow, divided into two different groups (control and laser) and collected at different times during the hospitalization of the patient. the group laser receive prophylactic laser therapy, in order to evaluate the effects of LLLT in inflammatory mediators (cytokines pro- and anti-inflammatory) as well as their effect on modulation of oxidative stress products and cell damage (nitric oxide, myeloperoxidase, interleukin-8).

Official Title
-----------------
Effect of Low-level Laser Therapy on Inflammatory Mediators Release During Chemotherapy-induced Oral Mucositis: a Randomized Study

Conditions
-----------------
Oral Mucositis

Intervention / Treatment
-----------------
* Radiation: Low-Level laser


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Schedule to receive myeloablative conditioning regimens using chemotherapy; oral mucosa lining intact on the first day of the conditioning regimen; Exclusion Criteria: Patients who presented with oral oral ulceration or erosion, active oral, viral, bacterial, or fungal infections on admission, or active oral bleeding which was uncontrollable during laser therapy or had required oral tracheal intubation during hospitalization in the HSCT Unit.

Ages Eligible for Study
-----------------
Minimum Age: 14 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-Level laser<br>In the laser group, an indium phosphide, galium and aluminum (InGaAIP) diode laser (660nm, 40mW, 0.16 J, 4 J/cm2) was used to irradiate oral mucosa. Subjects received the LLLT from the first day of the conditioning regimen and continued until D+7. Laser therapy was applied by a single dentist expertise in laser irradiation. The tip touched the mucosa of the lips, right and left buccal mucosa, right and left lateral tongue, ventral tongue and buccal floor, giving a total of 10 points per region. | Radiation: Low-Level laser<br>* Application of laser therapy in low power mucosa jugal right and left upper and lower labial mucosa, floor of the mouth, tongue side of the right and left and belly of the tongue.<br>|
| No Intervention: Control<br>In the control group, patients receive only the preventive protocol bone marrow transplant industry, consisting of mouthwashes and sodium fluoride. For ethical reasons, individuals who present oral mucositis grade 2 (WHO) will receive LLLT. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of Oral Mucositis | A trained clinical member of the team who was blind to the randomization allocation scores the degree of OM, during the hospitalization, in accordance to the World Health Organization (WHO) mucositis scale as follow: grade 0, no signs or symptoms; grade 1, painless ulcers, erythema, or mild soreness; grade 2, painful erythema, edema, or ulceration but the patient is able to eat; grade 3, mucosal damage and the patient is able to ingest only liquids; and grade 4, severe mucosa damage and the patient requires parenteral or enteral support. | On day of the transplant (D0), on seventh day after the transplant (D7) and discharge of the patient (HD) or until day 20 (D+20). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of Inflammatory Mediators | Saliva was collected in the morning, and patients were instructed to gargle with filtered water prior to collection. All the saliva produced in a 5-min interval was collected in a sterile tube. The saliva samples were then centrifuged at 1500 rpm for 10 min, and the total volumes measured with a micropipette. The supernatant was transferred to two other sterile tubes and a phosphate-buffered saline (PBS) solution (1: 1), containing protease inhibitors (0.1 mmol/1 EDTA, 0.001 mg/ml aprotinin A, and 0.05% Tween 20) which was added to one while the other maintained its pure saliva. All aliquots were frozen at -80°C to await analysis. | The samples were collected at three different moments of treatment: at the time of admission (AD), on the seventh day after transplantation (D+7), and on the day of discharge (with neutrophil >0.5 × 109/l for two consecutive days) (HD). | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Mucositis, inflammation, Chemotherapy, Hematopoietic stem cell transplant, Low level laser therapy, oxidative stress