Photobiomodulation Therapy Plus M-health in Head and Neck Cancer Patients: LAXER Study

Study Overview
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Brief Summary
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The Photobiomodulation therapy could have positive effects on quality of life and oral health in head and neck cancer survivors post-radiotherapy. The improvement in quality of life will be maintained after a follow-up period.

Detailed Description
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Many experts advocate the use of Photobiomodulation (PBM) therapy in patients with cancer and demand studies of higher methodological quality such as randomized controlled clinical trials. However, there is no consensus on the most effective dosimetry that allows us to establish an effective and safe approach to treat radiotherapy-induced xerostomia in head and neck cancer survivors. Finally, recent reviews highlight the importance of determining whether or not the effects of Photobiomodulation therapy are maintained after a follow-up period.

Official Title
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Photobiomodulation Therapy With M-health Tool for the Management of Oral Health and Quality of Life in Head and Neck Cancer Patients: LAXER Study

Conditions
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Head and Neck Cancer, Head and Neck Neoplasms, Xerostomia

Intervention / Treatment
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* Device: Energy density photobiomodulation (7.5)
* Device: Energy density photobiomodulation (3)
* Device: Sham placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with head and neck cancer. Persistent xerostomia after radiotherapy. ≥18 years. Irradiated with radiotherapy in the major salivary glands (parotid, submandibular and sublingual). Grade 3 for dry mouth in Common Terminology Criteria for Adverse Events, CTCAE (version 5.0). Have completed medical treatment with full response (complete remission) and receive medical clearance for participation. At least one month after radiotherapy completion, to reflect the possible presence of oral mucositis (sores) and/or radiodermatitis (inflammation) that limits adherence to treatment. No use of drugs/devices/products (pilocarpine, cevimeline, amifostine, oral devices, humidifiers or herbs) to prevent or treat xerostomia before inclusion in the study, OR constant usage (do not change type and dosage) during 2 months before inclusion in the study. Be able to access mobile apps or living with someone who has this ability. Exclusion Criteria: Relapse or metastasis. Karnofsky activity scale <60. Contraindications to PBM therapy (cardiac arrhythmias, pacemakers, photosensitivity, drugs with photosensitizing action, pregnancy). Patients with other comorbidities such as diabetes o polymedication.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group PBM_1<br>Energy density 7.5 J / cm2 for group PBM_1 | Device: Energy density photobiomodulation (7.5)<br>* A total of 22 points will be treated (extraoral and intraoral). 2 sessions per week, for 3 months (24 sessions in total). In addition, a mobile health application (LAXER) will be provided.<br>|
| Experimental: Group PBM_2<br>Energy density 3 J / cm2 for group PBM_2 | Device: Energy density photobiomodulation (3)<br>* A total of 22 points will be treated (extraoral and intraoral). 2 sessions per week, for 3 months (24 sessions in total). In addition, a mobile health application (LAXER) will be provided.<br>|
| Placebo Comparator: Placebo Control<br>The placebo control group will carry out the same protocol used in irradiated patients (including the use of protective glasses) using the same laser device to imitate a real irradiation; however, the device will be turned off and a recording of the emission sounds will be used to give the patient the hearing sensation of the laser therapy. | Device: Sham placebo<br>* In addition, a mobile health application (LAXER) will be provided.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| General and specific quality of life in head and neck cancer patients. | The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) version 3.0 assesses overall quality of life. Higher symptom scales/items and global health status scores mean worse and better outcomes, respectively. It is a valid questionnaire and widely used in cancer population. In addition, its specific head and neck module (EORTC QLQ-H & N35). Higher symptom scales/items scores mean a worse outcome. | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 
| Xerostomia severity. | Xerostomia Inventory consists of 11 items, the total score ranges from 11 to 55 points, and represents the severity of chronic xerostomia. Higher scores mean a worse outcome. | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 
| Nutritional and oral status. | Assesses through a Eating Assessment Tool questionnaire (EAT-10). Higher scores mean a worse outcome. | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 
| Visual Analogue Scale (VAS) for xerostomia and cervical/temporomandibular/shoulder pain | The subjective perception of xerostomia/pain from 0 to 10 will be registered. Higher scores mean a worse outcome. | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 
| Salivary flow rate | Determines the amount of stimulated and unstimulated saliva (ml) produced in 3 minutes. | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 
| Indicators of saliva | Quality of saliva with salivary biomarkers of salivary pH and cortisol, IgA, IL6, calcium, total protein, chloride, sodium / potassium and amylase / catalase activities using different laboratory kits. | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 
| Glandular ultrasound | It will monitor the morphology (size, echogeneity etc.) of the glands using ultrasound (Samsung HM70A echograph and Samsung Phased Array PE2-4 probe). | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 
| Maximum mouth opening | Determine maximum mouth opening (mm) as the inter-incisor distance using a sliding caliper. | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pressure pain threshold | Using a digital algometer in C5-C6 joint, upper trapezius, levator scapulae, masseter, temporalis, sternoclavicular joint and the tibialis anterior distal point. | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 
| Fitness Scale | The International Fitness Scale (IFIS) assesses overall fitness, cardio-respiratory, muscular, speed and flexibility dimensions using a 5-point Likert scale ('very poor', 'poor', 'average', 'good' and 'very good'). Higher scores mean a better outcome. | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 
| Mood status | The Spanish version of the Scale for Mood Assessment (EVEA) assesses mood state with a range of 0 to 10. It consists of 4 subscales: sadness-depression, anxiety, anger-hostility and happiness. Higher scores mean a worse outcome. | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 
| Quality of sleep | The Pittsburgh Sleep Quality Index will be used to evaluate the perceived quality of sleep in its Spanish version. Higher scores mean a worse outcome. | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 
| Physical activity level | The International Physical Activity Questionnaire (IPAQ-SF) is a tool that it will be used to evaluate physical activity. Different types of physical activities will be recorded (walking, moderate intensity activities, and vigorous intensity activities) during the last 7 days. | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 
| Functional capacity | Using walked distance (m) during 6-minutes walking test. | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 
| Risk of falls | Using time (s) during Test Up and Go (TUG). | Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Quality of Life, Neoplasms, Xerostomia, Low-Level Light Therapy, Telemedicine