Oral Mucositis
Conditions
Keywords
Mucositis, inflammation, Chemotherapy, Hematopoietic stem cell transplant, Low level laser therapy, oxidative stress
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).
Interventions
RADIATIONLow-Level laser
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.
Sponsors
Federal University of Minas Gerais
Araujo Jorge Hospital
Universidade Federal de Goias
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Oral Mucositis | 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). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Level of Inflammatory Mediators | 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). | 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. |
Participant flow
Recruitment details
This study enrolled patients admitted to the Bone Marrow Transplant Unit at Hospital Araújo Jorge/Goiás Combat Cancer Association (TMO/HAJ/ACCG), between February 2012 and July 2016.
Pre-assignment details
The patients recruited underwent block randomization and were allocated to two groups: one which would receive the low level laser therapy protocol (LLLT group) and one which would not, only the oral hygiene guidelines described above (control group).
Participants by arm
| Arm | Count |
|---|---|
| Low-Level Laser 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. 27 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. Low-Level laser: 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. | 27 |
| Control In the control group, 24 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. | 24 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 7 |
| Overall Study | Death | 3 | 3 |
Baseline characteristics
| Characteristic | Control | Total | Low-Level Laser |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 48 Participants | 24 Participants |
| Age, Continuous | 42 years STANDARD_DEVIATION 17.8 | 41 years STANDARD_DEVIATION 15.34 | 41 years STANDARD_DEVIATION 14.9 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Brazil | 24 participants | 51 participants | 27 participants |
| Sex: Female, Male Female | 13 Participants | 25 Participants | 12 Participants |
| Sex: Female, Male Male | 11 Participants | 26 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 34 | 3 / 34 |
| other Total, other adverse events | 0 / 34 | 0 / 34 |
| serious Total, serious adverse events | 4 / 34 | 7 / 34 |
Outcome results
Primary
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.
Time frame: 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).
Population: Oral Mucositis (OM) was evaluated on admission (AD), day 7 (D+7) and hospital discharge (HD) of the all patients. The severity of OM was scored in accordance with the World Health Organization (WHO), being represented by ordinal qualitative data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Low-Level Laser | Severity of Oral Mucositis | Admission | Grade 2 | 0 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Day 7 | Grade 3 | 0 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Day 7 | Grade 2 | 5 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Day 7 | Grade 4 | 0 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Admission | Grade 0 | 27 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Hospital Discharge | Grade 0 | 27 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Admission | Grade 3 | 0 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Hospital Discharge | Grade 1 | 0 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Day 7 | Grade 0 | 22 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Hospital Discharge | Grade 2 | 0 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Admission | Grade 1 | 0 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Hospital Discharge | Grade 3 | 0 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Day 7 | Grade 1 | 0 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Hospital Discharge | Grade 4 | 0 Participants |
| Low-Level Laser | Severity of Oral Mucositis | Admission | Grade 4 | 0 Participants |
| Control | Severity of Oral Mucositis | Hospital Discharge | Grade 4 | 0 Participants |
| Control | Severity of Oral Mucositis | Admission | Grade 1 | 0 Participants |
| Control | Severity of Oral Mucositis | Admission | Grade 3 | 0 Participants |
| Control | Severity of Oral Mucositis | Admission | Grade 4 | 0 Participants |
| Control | Severity of Oral Mucositis | Admission | Grade 0 | 24 Participants |
| Control | Severity of Oral Mucositis | Day 7 | Grade 0 | 0 Participants |
| Control | Severity of Oral Mucositis | Day 7 | Grade 1 | 10 Participants |
| Control | Severity of Oral Mucositis | Day 7 | Grade 2 | 10 Participants |
| Control | Severity of Oral Mucositis | Day 7 | Grade 3 | 4 Participants |
| Control | Severity of Oral Mucositis | Day 7 | Grade 4 | 0 Participants |
| Control | Severity of Oral Mucositis | Hospital Discharge | Grade 0 | 24 Participants |
| Control | Severity of Oral Mucositis | Hospital Discharge | Grade 1 | 0 Participants |
| Control | Severity of Oral Mucositis | Hospital Discharge | Grade 2 | 0 Participants |
| Control | Severity of Oral Mucositis | Hospital Discharge | Grade 3 | 0 Participants |
| Control | Severity of Oral Mucositis | Admission | Grade 2 | 0 Participants |
Comparison: The Pearson chi-square (χ2) or Fisher's Exact tests were used, at three different times (AD, D7, HD), to analyze the oral mucositis severity in the comparison between the LLLT and control groups. Statistical analysis was not performed for each grade of oral mucositis separately.p-value: <0.05Fisher Exact
Secondary
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.
Time frame: 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).
Population: Were admitted patients had to be at least 14 years of age, scheduled for autologous or allogeneic HSCT and planned treatment consisting of a myeloablative conditioning regimen with high-dose chemotherapy (HDC), without radiotherapy. Their oral mucosal lining had to be intact, and they had to have no infectious or other associated pathologies.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Low-Level Laser | Level of Inflammatory Mediators | CXCL-8 D7 | 730 Salivary Concentration (pg/mL) |
| Low-Level Laser | Level of Inflammatory Mediators | NO HD | 80 Salivary Concentration (pg/mL) |
| Low-Level Laser | Level of Inflammatory Mediators | NO AD | 127 Salivary Concentration (pg/mL) |
| Low-Level Laser | Level of Inflammatory Mediators | MPO AD | 62 Salivary Concentration (pg/mL) |
| Low-Level Laser | Level of Inflammatory Mediators | CXCL-8 HD | 1264 Salivary Concentration (pg/mL) |
| Low-Level Laser | Level of Inflammatory Mediators | MPO D7 | 7 Salivary Concentration (pg/mL) |
| Low-Level Laser | Level of Inflammatory Mediators | NO D7 | 68 Salivary Concentration (pg/mL) |
| Low-Level Laser | Level of Inflammatory Mediators | MPO HD | 61 Salivary Concentration (pg/mL) |
| Low-Level Laser | Level of Inflammatory Mediators | CXCL-8 AD | 1733 Salivary Concentration (pg/mL) |
| Control | Level of Inflammatory Mediators | MPO HD | 24 Salivary Concentration (pg/mL) |
| Control | Level of Inflammatory Mediators | CXCL-8 AD | 185 Salivary Concentration (pg/mL) |
| Control | Level of Inflammatory Mediators | CXCL-8 D7 | 201 Salivary Concentration (pg/mL) |
| Control | Level of Inflammatory Mediators | CXCL-8 HD | 195 Salivary Concentration (pg/mL) |
| Control | Level of Inflammatory Mediators | NO AD | 54 Salivary Concentration (pg/mL) |
| Control | Level of Inflammatory Mediators | NO D7 | 68 Salivary Concentration (pg/mL) |
| Control | Level of Inflammatory Mediators | NO HD | 53 Salivary Concentration (pg/mL) |
| Control | Level of Inflammatory Mediators | MPO AD | 60 Salivary Concentration (pg/mL) |
| Control | Level of Inflammatory Mediators | MPO D7 | 4 Salivary Concentration (pg/mL) |
p-value: <0.05Wilcoxon (Mann-Whitney)