Low-level Laser Therapy to Prevent Oral Mucositis in Head and Neck Patients

• Sponsor: Instituto Nacional de Cancer, Brazil (Other)
• Overall Status: Completed
• CT.gov ID: NCT01439724
• Collaborator: (none)
• Enrollment: 94
• Location: 1
• Arms: 2
• Duration (Months): 42
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

Oral mucositis remains a limiting factor in in head and neck squamous cell carcinomas patients treated with chemoradiation leading to pain, dysphagia, and weight loss. Low-level laser therapy emerges as a promising, preventive therapy of chemoradiation-induced OM. This study was designed to assess the efficacy of Low Level Laser Therapy (LLLT) in reducing the incidence and/or severity of oral mucositis.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of Nasopharynx; Squamous Cell Carcinoma of Oropharynx; Squamous Cell Carcinoma of Hypopharynx	Device: Low Level Laser Therapy- (DMC, São Paulo, Brazil); Device: Placebo (DMC, São Paulo, Brazil)	Phase 3

Detailed Description

Assuming oral mucositis grade 3 for placebo 0.4 (P0); laser group 0.15 (P1) ; β=0.2; α=0.05, sample size was 94 pts. From Jun 2007 to Dec 2010, 47 laser group and 47 placebo patients bearer of head and neck squamous cell carcinomas of nasopharynx, oropharynx and hypopharynx entered a prospective, randomized, double blind, placebo-controlled, phase III trial. chemoradiotherapy consisted of conventional radiotherapy 70.2 Gray (Gy) (1.8Gy/d, 5 times/wk)

• concurrent cisplatin 100 mg/m2 every 3 weeks. The primary end point was the incidence of grade 3-4 oral mucositis. The Low-level laser therapy used daily, was a diode indium phosphide, gallium and aluminum (InGaAlP), 660nm-100 milliwatts (mW)-4 Joules (J)/cm²(DMC, São Carlos, São Paulo, Brazil). Oral mucositis evaluation was done by WHO and Oral Mucositis Assessment Scale (OMAS) scale.

Study Design

• Study Type: Interventional
• Actual Enrollment: 94 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Phase III Trial of Low-level Laser Therapy to Prevent Induced Oral Mucositis in Head and Neck Cancer Patients Submitted to Concurrent Chemoradiation
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Patients in the placebo group received the same treatment during the same time, but in this case the laser tip produced no light.	Device: Placebo (DMC, São Paulo, Brazil); The placebo (DMC, São Paulo, Brazil) was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.Patients in the placebo group received the same treatment during the same time, but in this case the laser tip produced no light.; Other Names: Low power laser therapy Low energy laser therapy
Experimental: Low Level Laser Therapy The investigators used a Low Level Laser Therapy, diode laser (DMC, São Paulo, Brazil) InGaAlP (indium phosphide, gallium and aluminum), with 100mW, 4J/cm ², with an area of 0.24 cm ². The laser was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.	Device: Low Level Laser Therapy- (DMC, São Paulo, Brazil); Diode laser (DMC,São Paulo, Brazil) InGaAlP (indium phosphide, gallium and aluminum), with 100 mW, 4J/cm ², with an area of 0.24 cm ². The laser was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.; Other Names: Low Power Laser Therapy Low Energy Laser Therapy

Outcome Measures

Primary Outcome Measures

1. Incidence and / or Severity of Oral Mucositis [7 weeks]

   The oral cavities of all patients were evaluated daily, from the first day until the last day of treatment. We used the scales of mucositis of the World Health Organization (WHO) and the Oral Mucositis Assessment Scale (OMAS) and a visual analogue scale (VAS) for pain assessment.

Secondary Outcome Measures

1. Oral Mucositis Survival Free, Pain, Opioid Treatment, Hospitalization, Treatment Interruption, Treatment Delay, Patient Weight Loss, Nasogastric Tube or of a Gastrostomy. [7 weeks]

   Oral mucositis survival free, pain, opioid treatment, hospitalization, treatment interruption, treatment delay, patient weight loss, nasogastric tube or of a gastrostomy.The oral cavities of all patients were evaluated, from the first day to the last day of treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥ 18 years

• Histological diagnosis of squamous cell carcinoma (nasopharynx, oropharynx and hypopharynx)

• Candidates for surgery or treatment for organ preservation

• Performance status (PS) of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG)

• Indication for radiotherapy and concurrent platinum-based chemotherapy

• Oral mucosa intact

• Agree to follow the protocol of oral hygiene

• Informed consent.

Exclusion Criteria:

• Patients using medication for treatment and or prevention of mucositis

• Patients incapable of treatment compliance or of performing the protocol of oral hygiene

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Instituto Nacional de Cancer	Rio de Janeiro		Brazil	20231-050

Sponsors and Collaborators

• Instituto Nacional de Cancer, Brazil

Investigators

• Principal Investigator: Heliton S Antunes, DDS, PhD, Instituto Nacional de Cancer, Brazil
• Study Director: Carlos G Ferreira, MD, PhD, Instituto Nacional de Cancer, Brazil

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for more information about Instituto Nacional de Cancer- Brazil

Publications

None provided.

• Responsible Party: Instituto Nacional de Cancer, Brazil
• ClinicalTrials.gov Identifier: NCT01439724
• Other Study ID Numbers: INCABrazil; Protocol 17/2007
• First Posted: Sep 23, 2011
• Last Update Posted: Apr 11, 2014
• Last Verified: Feb 1, 2013

• Keywords provided by Instituto Nacional de Cancer, Brazil: Oral mucositis; Low Level Laser Therapy; Head and neck cancer
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Nasopharyngeal Carcinoma; Mucositis; Stomatitis

Study Results

Participant Flow

Arm/Group Title	Placebo	Low Level Laser Therapy
Arm/Group Description	Patients in the placebo group received the same treatment during the same time, but in this case the laser tip produced no light. Placebo (DMC, São Paulo, Brazil): The placebo (DMC, São Paulo, Brazil) was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.Patients in the placebo group received the same treatment during the same time, but in this case the laser tip produced no light.	The investigators used a diode laser (DMC, São Paulo, Brazil) InGaAlP (indium phosphide, gallium and aluminum), with 100mW, 4 Joules(J)/cm ², with an area of 0.24 cm ². The laser was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region. Low Level Laser Therapy- (DMC, São Paulo, Brazil): Diode laser (DMC,São Paulo, Brazil) InGaAlP (indium phosphide, gallium and aluminum), with 100 mW, 4J/cm ², with an area of 0.24 cm ². The laser was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.
Period Title: Overall Study
STARTED	47	47
COMPLETED	38	39
NOT COMPLETED	9	8

Baseline Characteristics

Arm/Group Title	Placebo	Low Level Laser Therapy	Total
Arm/Group Description	Patients in the placebo group received the same treatment during the same time, but in this case the laser tip produced no light. Placebo (DMC, São Paulo, Brazil): The placebo (DMC, São Paulo, Brazil) was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.Patients in the placebo group received the same treatment during the same time, but in this case the laser tip produced no light.	The investigators used a diode laser (DMC, São Paulo, Brazil) InGaAlP (indium phosphide, gallium and aluminum), with 100 mW, 4J/cm ², with an area of 0.24 cm ². The laser was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region. Low Level Laser Therapy- (DMC, São Paulo, Brazil): Diode laser (DMC,São Paulo, Brazil) InGaAlP (indium phosphide, gallium and aluminum), with 100 mW, 4J/cm ², with an area of 0.24 cm ². The laser was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.	Total of all reporting groups
Overall Participants	47	47	94
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.7 (8.6)	53.5 (6.9)	54.6 (7.7)
Sex: Female, Male (Count of Participants)
Female	7 14.9%	5 10.6%	12 12.8%
Male	40 85.1%	42 89.4%	82 87.2%
Region of Enrollment (participants) [Number]
Brazil	47 100%	47 100%	94 100%

Outcome Measures

1. Primary Outcome

Title	Incidence and / or Severity of Oral Mucositis
Description	The oral cavities of all patients were evaluated daily, from the first day until the last day of treatment. We used the scales of mucositis of the World Health Organization (WHO) and the Oral Mucositis Assessment Scale (OMAS) and a visual analogue scale (VAS) for pain assessment.
Time Frame	7 weeks

Outcome Measure Data

Analysis Population Description

Data related to the primary endpoint were handled in a per protocol treatment analysis.

Arm/Group Title	Placebo	Low Level Laser Therapy
Arm/Group Description	Patients in the placebo group received the same treatment during the same time, but in this case the laser tip produced no light. Placebo (DMC, São Paulo, Brazil): The placebo (DMC, São Paulo, Brazil) was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.Patients in the placebo group received the same treatment during the same time, but in this case the laser tip produced no light.	The investigators used a diode laser (DMC, São Paulo, Brazil) InGaAlP (indium phosphide, gallium and aluminum), with 100 mW, 4J/cm ², with an area of 0.24 cm ². The laser was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region. Low Level Laser Therapy- (DMC, São Paulo, Brazil): Diode laser (DMC,São Paulo, Brazil) InGaAlP (indium phosphide, gallium and aluminum), with 100 mW, 4J/cm ², with an area of 0.24 cm ². The laser was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.
Measure Participants	47	47
Number [Grade 3-4 oral mucositis]	19	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Low Level Laser Therapy
	Comments	The primary end point of the study was the incidence of grade 3-4 oral mucositis (OM) according to the WHO scale. Assuming an α =0.05 and a β = 0.20, with the estimates of proportion being 0.40 for placebo (P0) and 0.15 for LLLT (P1) a total of 94 patients were evaluated. One-sided test error was the basis for the sample size determination and all the reported P-values were derived from two-sided statistical tests. P-values less than or equal to 0.05 were considered statistically significant.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.158
	Confidence Interval	(2-Sided) 95%; 0.050 to 0.498
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Oral Mucositis Survival Free, Pain, Opioid Treatment, Hospitalization, Treatment Interruption, Treatment Delay, Patient Weight Loss, Nasogastric Tube or of a Gastrostomy.
Description	Oral mucositis survival free, pain, opioid treatment, hospitalization, treatment interruption, treatment delay, patient weight loss, nasogastric tube or of a gastrostomy.The oral cavities of all patients were evaluated, from the first day to the last day of treatment.
Time Frame	7 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	3 years
Arm/Group Title	Placebo		Low Level Laser Therapy
Arm/Group Description	Patients in the placebo group received the same treatment during the same time, but in this case the laser tip produced no light. Placebo (DMC, São Paulo, Brazil): The placebo (DMC, São Paulo, Brazil) was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.Patients in the placebo group received the same treatment during the same time, but in this case the laser tip produced no light.		The investigators used a diode laser (DMC, São Paulo, Brazil) InGaAlP (indium phosphide, gallium and aluminum), with 100 mW, 4J/cm ², with an area of 0.24 cm ². The laser was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region. Low Level Laser Therapy- (DMC, São Paulo, Brazil): Diode laser (DMC,São Paulo, Brazil) InGaAlP (indium phosphide, gallium and aluminum), with 100 mW, 4J/cm ², with an area of 0.24 cm ². The laser was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.
All Cause Mortality
	Placebo		Low Level Laser Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Low Level Laser Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/47 (36.2%)		15/47 (31.9%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders	4/47 (8.5%)	4	0/47 (0%)	0
Ear and labyrinth disorders
Ear and labyrinth disorders	3/47 (6.4%)	3	4/47 (8.5%)	4
Infections and infestations
Pneumonia	1/47 (2.1%)	1	1/47 (2.1%)	1
Renal and urinary disorders
Renal and urinary disorders	5/47 (10.6%)	5	3/47 (6.4%)	3
Skin and subcutaneous tissue disorders
Radiodermatitis	4/47 (8.5%)	4	7/47 (14.9%)	7
Other (Not Including Serious) Adverse Events
	Placebo		Low Level Laser Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/47 (36.2%)		10/47 (21.3%)
Gastrointestinal disorders
Gastrointestinal disorders	17/47 (36.2%)	17	10/47 (21.3%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.