Trial Outcomes & Findings for Low-level Laser Therapy on Inflammatory Mediators During Chemotherapy-induced Oral Mucositis (NCT NCT02050373)
NCT ID: NCT02050373
Last Updated: 2021-01-22
Results Overview
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.
COMPLETED
NA
51 participants
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).
2021-01-22
Participant Flow
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.
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).
Participant milestones
| Measure |
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. 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.
|
Controll
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.
|
|---|---|---|
|
Overall Study
STARTED
|
34
|
34
|
|
Overall Study
COMPLETED
|
27
|
24
|
|
Overall Study
NOT COMPLETED
|
7
|
10
|
Reasons for withdrawal
| Measure |
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. 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.
|
Controll
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
7
|
|
Overall Study
Death
|
3
|
3
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Low-Level Laser
n=27 Participants
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.
|
Control
n=24 Participants
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.
|
Total
n=51 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
2 Participants
n=27 Participants
|
0 Participants
n=24 Participants
|
2 Participants
n=51 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
24 Participants
n=27 Participants
|
24 Participants
n=24 Participants
|
48 Participants
n=51 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=27 Participants
|
0 Participants
n=24 Participants
|
1 Participants
n=51 Participants
|
|
Age, Continuous
|
41 years
STANDARD_DEVIATION 14.9 • n=27 Participants
|
42 years
STANDARD_DEVIATION 17.8 • n=24 Participants
|
41 years
STANDARD_DEVIATION 15.34 • n=51 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=27 Participants
|
13 Participants
n=24 Participants
|
25 Participants
n=51 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=27 Participants
|
11 Participants
n=24 Participants
|
26 Participants
n=51 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Brazil
|
27 participants
n=27 Participants
|
24 participants
n=24 Participants
|
51 participants
n=51 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Low-Level Laser
n=27 Participants
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. 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.
|
Control
n=24 Participants
In the control group, patients receive instructions on the oral hygiene protocol (dental brushing after meals, dental flossing once a day and an alcohol-free 0.12% mouthwash twice a day). For ethical reasons, individuals who present oral mucositis grade 2 (WHO) will receive LLLT.
|
|---|---|---|
|
Severity of Oral Mucositis
Admission · Grade 0
|
27 Participants
|
24 Participants
|
|
Severity of Oral Mucositis
Admission · Grade 1
|
0 Participants
|
0 Participants
|
|
Severity of Oral Mucositis
Admission · Grade 2
|
0 Participants
|
0 Participants
|
|
Severity of Oral Mucositis
Admission · Grade 3
|
0 Participants
|
0 Participants
|
|
Severity of Oral Mucositis
Admission · Grade 4
|
0 Participants
|
0 Participants
|
|
Severity of Oral Mucositis
Day 7 · Grade 0
|
22 Participants
|
0 Participants
|
|
Severity of Oral Mucositis
Day 7 · Grade 1
|
0 Participants
|
10 Participants
|
|
Severity of Oral Mucositis
Day 7 · Grade 2
|
5 Participants
|
10 Participants
|
|
Severity of Oral Mucositis
Day 7 · Grade 3
|
0 Participants
|
4 Participants
|
|
Severity of Oral Mucositis
Day 7 · Grade 4
|
0 Participants
|
0 Participants
|
|
Severity of Oral Mucositis
Hospital Discharge · Grade 0
|
27 Participants
|
24 Participants
|
|
Severity of Oral Mucositis
Hospital Discharge · Grade 1
|
0 Participants
|
0 Participants
|
|
Severity of Oral Mucositis
Hospital Discharge · Grade 2
|
0 Participants
|
0 Participants
|
|
Severity of Oral Mucositis
Hospital Discharge · Grade 3
|
0 Participants
|
0 Participants
|
|
Severity of Oral Mucositis
Hospital Discharge · Grade 4
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Low-Level Laser
n=27 Participants
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. 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.
|
Control
n=24 Participants
In the control group, patients receive instructions on the oral hygiene protocol (dental brushing after meals, dental flossing once a day and an alcohol-free 0.12% mouthwash twice a day). For ethical reasons, individuals who present oral mucositis grade 2 (WHO) will receive LLLT.
|
|---|---|---|
|
Level of Inflammatory Mediators
CXCL-8 AD
|
1733 Salivary Concentration (pg/mL)
Interval 853.0 to 4057.0
|
185 Salivary Concentration (pg/mL)
Interval 70.0 to 267.0
|
|
Level of Inflammatory Mediators
CXCL-8 D7
|
730 Salivary Concentration (pg/mL)
Interval 182.0 to 1964.0
|
201 Salivary Concentration (pg/mL)
Interval 119.0 to 414.0
|
|
Level of Inflammatory Mediators
CXCL-8 HD
|
1264 Salivary Concentration (pg/mL)
Interval 131.0 to 7770.0
|
195 Salivary Concentration (pg/mL)
Interval 143.0 to 300.0
|
|
Level of Inflammatory Mediators
NO AD
|
127 Salivary Concentration (pg/mL)
Interval 84.0 to 205.0
|
54 Salivary Concentration (pg/mL)
Interval 23.0 to 104.0
|
|
Level of Inflammatory Mediators
NO D7
|
68 Salivary Concentration (pg/mL)
Interval 36.0 to 253.0
|
68 Salivary Concentration (pg/mL)
Interval 17.0 to 89.0
|
|
Level of Inflammatory Mediators
NO HD
|
80 Salivary Concentration (pg/mL)
Interval 57.0 to 207.0
|
53 Salivary Concentration (pg/mL)
Interval 12.0 to 98.0
|
|
Level of Inflammatory Mediators
MPO AD
|
62 Salivary Concentration (pg/mL)
Interval 59.0 to 62.0
|
60 Salivary Concentration (pg/mL)
Interval 58.0 to 60.0
|
|
Level of Inflammatory Mediators
MPO D7
|
7 Salivary Concentration (pg/mL)
Interval 1.0 to 27.0
|
4 Salivary Concentration (pg/mL)
Interval 2.0 to 8.0
|
|
Level of Inflammatory Mediators
MPO HD
|
61 Salivary Concentration (pg/mL)
Interval 60.0 to 62.0
|
24 Salivary Concentration (pg/mL)
Interval 14.0 to 52.0
|
Adverse Events
Low-Level Laser
Control
Serious adverse events
| Measure |
Low-Level Laser
n=34 participants at risk
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. 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.
|
Control
n=34 participants at risk
In the control group, patients receive instructions on the oral hygiene protocol (dental brushing after meals, dental flossing once a day and an alcohol-free 0.12% mouthwash twice a day). For ethical reasons, individuals who present oral mucositis grade 2 (WHO) will receive LLLT.
|
|---|---|---|
|
General disorders
Need for oral tracheal intubation during hospitalization
|
8.8%
3/34 • The patients was evaluated daily from the day of transplantation or infusion of bone marrow (D0) until day 20 (D+20) or discharge of the patient.
|
20.6%
7/34 • The patients was evaluated daily from the day of transplantation or infusion of bone marrow (D0) until day 20 (D+20) or discharge of the patient.
|
|
Nervous system disorders
Mental confusion
|
2.9%
1/34 • The patients was evaluated daily from the day of transplantation or infusion of bone marrow (D0) until day 20 (D+20) or discharge of the patient.
|
0.00%
0/34 • The patients was evaluated daily from the day of transplantation or infusion of bone marrow (D0) until day 20 (D+20) or discharge of the patient.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place