Oral Mucositis and Laser Therapy Associated With Photodynamic Therapy

Oral Mucositis Clinical Trial

— OMLTPT  

Official title:

Laser Therapy Associated With Photodynamic Therapy in the Treatment of Oral Mucositis Induced by Chemotherapy in Young Patients: Randomized Blind Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02555501
• Other study ID #: MCCF-060264-AM
• Status: Completed
• Phase: Phase 3
• First received: September 17, 2015
• Last updated: September 18, 2015
• Start date: October 2014
• Est. completion date: September 2015

Study information

• Verified date: September 2015
• Source: Universidade Ceuma
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brasil: National Health Surveillance Agency
• Study type: Interventional

Clinical Trial Summary

The aim of the study was to evaluate the therapeutic action through the diameter of the lesion, of low level laser (LLL) associated to photodynamic therapy (PDT) in oral mucositis (OM) lesions, in young patients. A randomized clinical trial blinded, split-mouth was performed. The study sample consisted of 15 cancer patients (3-16 years old) of Aldenora Bello Hospital (São Luís, Maranhão, Brazil). Random allocation by lot of treatments (PDT + LLL and LLL) to quadrants of the oral cavity was performed, and the patient was his own control. Patients were masked about therapy performed on each side of the arch. The evaluation period of both therapeutic regimens was 8 days, and the outcome assessed was the lesion size (measured in cm²). Friedman and Wilcoxon tests were applied and the effect magnitude calculated. The significance level was 5%. Statistically significant difference was observed between the groups for the lesion diameter of the 6th to the 8th day (greater regression of lesion size for the PDT + LLL group), which was confirmed by a difference magnitude moderated. Based on the findings, it is concluded that PDT + LLL showed greater therapeutic effect when compared to LLL in reducing the severity of OM lesions.

Description:

The blind randomized clinical trial included 18 young patients, between 3 and 16 years old, undergoing chemotherapy or chemo/radiological the pediatric ward of Aldenora Bello Hospital in São Luís (Maranhão, Brazil). The study was conducted from October/2014 to January/2015. It was adopted as inclusion criteria patients between 3 and 18 years old, in the inductive phase of chemotherapy, with oral mucositis (OM) and bilateral lesions.

A mouth split model was conducted, and the patients were their own controls. The entry of the patients in the study occurred consecutively. To each patient, the operator/examiner drafted an envelope containing treatments to either side, being masked patient about the treatment of each side: PDT (photosensitized and low level laser) + low level laser; Low level laser].

The following parameters were used for the calculation of sample size: 95% confidence level, 80% statistical power and minimal difference of 0.82 point in the lesions diameter detected between paired samples. A "n" sample minimum of 14 was determined for each treatment. In order to compensate for possible losses, 18 patients were treated.

The treatments (PDT and low level laser; Low level laser) were performed in a hospital bed. Prior to treatment, the OM lesions were evaluated and a lesion on each side was chosen. Lesions should be located at the same site on both sides. The chosen site was the lip mucosa. Before the procedure, the patient was instructed as to brushing and not using mouthwashes, followed by cleaning of the oral cavity with gauze and distilled water. Two days before the laser treatment, the side of the oral cavity chosen for the experimental treatment (PDT and low level laser) was pigmented with the photosensitizer (aqueous solution of 0.005% methylene blue). A ball of sterile cotton was soaked in the dye solution and placed in the center of the lesion. Photosensitizer remained in the place for 5 minutes (pre-irradiation period). Then, to activate the dye, the lesion was irradiated with red light (InGaAlP / phosphide and Indium, Gallium and potassium) (Flash Laser III, DMC, São Carlos, São Paulo, Brazil), with a wavelength of 660 nm, for a period 90 seconds, with a power of 100mW, to 1cm away, according to the manufacturer's specifications. The lesion on the opposite side was treated with ball of sterile cotton soaked in distilled water and the laser unit placed on the lesion without activation of the light. This procedure aimed to mask the patient about the side that received the experimental therapy (PDT and low level laser). This masking was possible because the experimental solution is insipid, very soluble and thus leaves no residue.

From the 3rd to the 10th day (total of 8 days) was carried out only laser therapy on both sides. Lesions were evaluated until the 8th day. After the 8th day of assessment, the lesions were only treated to a complete remission as well as other lesions present in the oral cavity. For laser therapy was first used infrared emitter laser unit with active medium AsGaAl (Gallium Arsenide and Aluminium), with wavelength of 808nm, for analgesia. Then, the investigators used the red emitter, whose active medium was the InGaAlP (phosphide and Indium, Gallium and Potassium), with wavelength of 660nm to photobiomodulation. For both units emitting laser, the tip of the device was closed against the edges of the lesion, perpendicular to the tissue. A irradiation was continuous and the application punctual (10 seconds). The distance between the points of irradiation was about 1cm. The energy delivered was 4J per point of application. The interval between sessions was 24 hours.

The tip of the laser was disinfected with 70% alcohol solution and wrapped with a plastic film. Patients and operators wore glasses for eye protection.

A questionnaire containing demographic, socioeconomic and type of treatment for cancer was applied to parents and children. White blood cell count and platelets (beginning and end of the inductive phase of QT) were extracted from medical records.

The assessed outcome measure was the diameter of the lesion (in cm2). The areas of the lesions were measured with a flexible ruler (record made in cm2) by the operator/examiner from the start of treatment with exclusive laser therapy (3rd day). This procedure was repeated on subsequent days until the 8th day of laser treatment. The measurement of the lesions occurred prior to laser therapy applications.

The Friedman test was used for multiple comparisons within groups (different times of treatment). Paired evaluation between each two moments was evaluated using the Wilcoxon test, with significance corrected by Bonferroni test (p = 0.0071). The Wilcoxon test was used to compare the diameter of the lesion, every day, between the PDT + Low level laser and Low level laser groups (dependent samples/split-mouth). It calculated the effect magnitude (d) of standardized differences between averages of two groups. The level of significance for analysis was 5%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 18 Years

Eligibility

Inclusion Criteria:

• Patients between 3 and 18 years old

• Patients on chemotherapy inductive phase

• Patients with oral mucositis and bilateral lesions

Exclusion Criteria:

• Patients outside the established age

• Patients who are in other phases of chemotherapy

• Patients who did not have bilateral lesions

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Mucositis
• Oral Mucositis
• Stomatitis

Intervention

Other:
• PDT + Low level laser
Two days before the laser treatment, the side of the oral cavity chosen for the experimental treatment was pigmented with aqueous solution of 0.005% methylene blue. A ball of sterile cotton was soaked in the dye solution and placed in the center of the lesion. Photosensitizer remained in the place for 5 minutes (pre-irradiation period). Then, to activate the dye, the lesion was irradiated with red light (InGaAlP / phosphide and Indium, Gallium and potassium). From the 3rd to the 10th day was carried out only laser therapy. For laser therapy was first used infrared emitter laser unit with active medium AsGaAl (Gallium Arsenide and Aluminium). Then, we used the red emitter, whose active medium was the InGaAlP (phosphide and Indium, Gallium and Potassium).

Radiation:
• Low level laser
Two days before the laser treatment, the lesion of the side of the oral cavity chosen for the control treatment was treated with ball of sterile cotton soaked in distilled water and the laser unit placed on the lesion without activation of the light. From the 3rd to the 10th day was carried out laser therapy. For laser therapy was first used infrared emitter laser unit with active medium AsGaAl (Gallium Arsenide and Aluminium). Then, we used the red emitter, whose active medium was the InGaAlP (phosphide and Indium, Gallium and Potassium).

Locations

Country	Name	City	State
Brazil	Hospital Aldenora Bello	São Luís	Maranhão

Sponsors (2)

Lead Sponsor	Collaborator
Universidade Ceuma	Fundação de Amparo à Pesquisa e Desenvolvimento Científico do Maranhão

Country where clinical trial is conducted

Brazil, 

References & Publications (37)

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* Note: There are 37 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lesion size	Lesion size measured in cm²	8 days	Yes