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

• ClinicalTrials.gov Identifier: NCT05106608
• Recruitment Status: Recruiting
• First Posted: November 4, 2021
• Last Update Posted: January 5, 2024
• Sponsor: Universidad de Granada
• Information provided by (Responsible Party): Noelia Galiano-Castillo, Universidad de Granada

Tracking Information

• First Submitted Date: October 10, 2021
• First Posted Date: November 4, 2021
• Last Update Posted Date: January 5, 2024
• Actual Study Start Date: July 13, 2022
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 29, 2023)

• General and specific quality of life. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) version 3.0 comprises 30 items on 5 functional scales, 3 symptom scales, 6 single items and a global health scale measured by a 4-point Likert scale with a total score ranging from 0 to 100. Higher scores on the functional and global health scales indicate better functioning or QoL, respectively, but higher scores on the symptom scales or single items indicate a high level of symptoms. In addition, the specific head and neck module (EORTC QLQ-H&N35) will be used; this module comprises 35 items on 7 multi-item scales and 11 single items scored from 0 to 100. Higher scores indicate more symptoms.
• Oral Health. Severity of xerostomia. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  Xerostomia Inventory consists of 11 items (score range 1-5) with a total score ranging from 11 to 55 points to rate the severity of chronic xerostomia. A higher score indicates more severe xerostomia.
• Oral Health. Dysphagia. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  Eating Assessment Tool questionnaire (EAT-10) consists of 10 items related to swallowing difficulties (score range 0-4, 0=no problem, 4=severe problem), with a total score of 3 or higher indicating dysphagia.
• Oral Health. Perceived xerostomia. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  A numeric visual analog scale (VAS) will be used with with a grade ranging from 0 (no symptoms) to 10 (the worst possible symptoms).
• Oral Health. Degree of mouth opening. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  The degree of mouth opening will be determined by the range of motion (ROM) using a sliding caliper, which will measure the maximal interincisal distance in millimeters.
• Oral Health. Clinical physical findings (dryness in the mouth). [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  A total of 10 examples of clinical physical findings where each one represents a feature of dryness in the mouth will be administered through the Clinical Oral Dryness Score (CODS). A score of 2 or more indicates significant oral dryness.
• Oral Health. Regional oral dryness. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  Regional Oral Dryness Inventory (RODI) quantifies the severity of dryness at 9 different locations in the oral cavity and is represented by 9 illustrations. Patients will indicate the severity of perceived oral dryness using a 5-point Likert scale (1=none, 5=severe).
• Salivary secretion. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  The 5-min unstimulated and 5-min stimulated salivary flow rates (SFRs) will be calculated (ml/min) and the volume of each sample will be also calculated (in microlitres). Samples from unstimulated saliva will be used to analyse salivary biomarkers, such as proteins (e.g., antibodies), calcium concentration and pH, using commercial kits.
• Salivary gland ultrasound assessment. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  The morphology of the parotid and submandibular glands will be assessed using 2D echography (Samsung HM70A echograph) to quantify changes in size in three dimensions.

Original Primary Outcome Measures (submitted: October 22, 2021)

• General and specific quality of life in head and neck cancer patients. [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  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.
• Xerostomia severity. [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  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.
• Nutritional and oral status. [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  Assesses through a Eating Assessment Tool questionnaire (EAT-10). Higher scores mean a worse outcome.
• Visual Analogue Scale (VAS) for xerostomia and cervical/temporomandibular/shoulder pain [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  The subjective perception of xerostomia/pain from 0 to 10 will be registered. Higher scores mean a worse outcome.
• Salivary flow rate [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  Determines the amount of stimulated and unstimulated saliva (ml) produced in 3 minutes.
• Indicators of saliva [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  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.
• Glandular ultrasound [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  It will monitor the morphology (size, echogeneity etc.) of the glands using ultrasound (Samsung HM70A echograph and Samsung Phased Array PE2-4 probe).
• Maximum mouth opening [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  Determine maximum mouth opening (mm) as the inter-incisor distance using a sliding caliper.

Current Secondary Outcome Measures (submitted: December 29, 2023)

• Pressure pain threshold. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  An electronic algometer (SENSEBox System, Somedic AB, Sösdala, SE) will be used to assess pain at 7 body sites bilaterally: the C5-C6 joint, upper trapezius, elevator scapulae, masseter, temporalis, sternoclavicular joint and tibialis anterior distal point. The mean of the three measurements will be considered.
• Functional Performance. Functional capacity. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  The 6-minute walk test (6MWT) will be used; the maximum walked distance (meters) that patients are able to walk in a 30-meter linear corridor will be quantified. A longer distance indicates better functional capacity.
• Functional Performance. Mobility/fall risk. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  The timed up-and-go (TUG) test will be used; patients sit back in a chair and walk toward a cone located 3 meters away as quickly as possible. The time (seconds) needed will be registered 2 times, with a shorter time indicating better mobility.
• Functional Performance. Perceived fitness status. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  The International Fitness Scale (IFIS) assesses overall fitness, cardio-respiratory fitness, muscular strength, speed/agility and flexibility dimensions, using a 5-point Likert scale (1=very poor, 2=poor, 3=average, 4=good, 5=very good).
• Functional Performance. Physical activity level. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  The International Physical Activity Questionnaire Short Form (IPAQ-SF), a self-reported validated questionnaire in patients with cancer that records the activities of the previous 7 days according to intensity level.
• Mood. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  The Spanish version of the Scale for Mood Assessment (EVEA) will also be used and comprises 4 subscales with good reliability (sadness-depression, anxiety, anger-hostility and happiness); the items range from 0 to 10 (0=nothing, 10=much).
• Sleep quality. [ Time Frame: Change from Baseline (at the beginning of the study) to 12 weeks (postintervention) and to 6 months (follow-up). ]
  Sleep quality will be measured using the Pittsburgh Sleep Quality Index (PSQI), a validated questionnaire that includes 19 self-related questions ranging from 0 to 3. The total score ranges from 0 to 21, and a lower score indicates better quality of sleep.

Original Secondary Outcome Measures (submitted: October 22, 2021)

• Pressure pain threshold [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  Using a digital algometer in C5-C6 joint, upper trapezius, levator scapulae, masseter, temporalis, sternoclavicular joint and the tibialis anterior distal point.
• Fitness Scale [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  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.
• Mood status [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  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.
• Quality of sleep [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  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.
• Physical activity level [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  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.
• Functional capacity [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  Using walked distance (m) during 6-minutes walking test.
• Risk of falls [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  Using time (s) during Test Up and Go (TUG).

Current Other Pre-specified Outcome Measures (submitted: December 29, 2023)

• Safety and adverse events (AEs). [ Time Frame: 12 weeks (postintervention) ]
  Safety will be assessed by the occurrence of any AEs using CTCAE version 5.0.
• Satisfaction questionnaire. [ Time Frame: 12 weeks (postintervention) ]
  Satisfaction will be registered by a questionnaire previously used in other clinical settings at the end of the intervention.

Original Other Pre-specified Outcome Measures (submitted: October 22, 2021)

• Safety and adverse events [ Time Frame: Change from Baseline to 12 weeks (after intervention) and to 6 months (follow-up). ]
  Each adverse event is characterized by severity (grade 1 [mild] to 5 [death]), expectation (expected or unexpected) and potential relationship with participation in the study (unrelated, possibly related, or related to the study) using Common Terminology Criteria for adverse events (version 5.0).
• Satisfaction questionnaire [ Time Frame: 12 weeks (after intervention) ]
  Each patient will mark his/her experience after Photobiomodulation therapy and L3AXER app. Higher scores mean a better outcome.

Descriptive Information

• Brief Title: Photobiomodulation Therapy Plus M-health in Head and Neck Cancer Patients: LAXER Study
• Official Title: Photobiomodulation Therapy With M-health Tool for the Management of Oral Health and Quality of Life in Head and Neck Cancer Patients: LAXER Study
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized controlled trial

Masking: Double (Participant, Outcomes Assessor)
Masking Description:

Participants who meet the inclusion and exclusion criteria will be randomized to one of the three study groups using a random number generation program (www.randomizer.org). The randomization sequence will be prepared by a member external to the investigation to respect the masking in terms of randomization of the participants, thus reducing the risk of bias during the evaluations. Therefore both patients and evaluator will be masked.

Primary Purpose: Treatment

Condition

• Head and Neck Cancer
• Head and Neck Neoplasms
• Xerostomia

Intervention

• Device: Energy density photobiomodulation (7.5)
  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.
• Device: Energy density photobiomodulation (3)
  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.
• Device: Sham placebo
  In addition, a mobile health application (LAXER) will be provided.

Study Arms

• Experimental: Group PBM_1
  Energy density 7.5 J / cm2 for group PBM_1
  Intervention: Device: Energy density photobiomodulation (7.5)
• Experimental: Group PBM_2
  Energy density 3 J / cm2 for group PBM_2
  Intervention: Device: Energy density photobiomodulation (3)
• Placebo Comparator: Placebo Control
  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.
  Intervention: Device: Sham placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 22, 2021): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2025
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Patients will be included in the study if they meet the following inclusion criteria:

• men or women aged 18 years or older and were diagnosed with HNC.
• chronic xerostomia.
• received RT in the parotid, submandibular and/or sublingual salivary glands.
• grade 3 oral dryness according to the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE).
• medical treatment completed and in complete remission.
• received medical clearance for participation in this study.
• at least one month passed since the end of RT to avoid the possible presence of oral mucositis and/or radiodermatitis, which limits adherence to treatment and maximum 36 months.
• no history of drugs/devices/products (pilocarpine, cevimeline, amifostine, oral devices, humidifiers, or herbs) to prevent or treat xerostomia prior to study inclusion or no change in their use (no change in type or dose) for two months prior to study inclusion.
• and able to access mobile applications or living with someone who has this ability.

The exclusion criteria will be as follows:

• patients with metastases.
• a score <60 on the Karnofsky Performance Status Scale.
• contraindications to receiving PBM therapy (e.g., cardiac arrhythmias, pacemakers, photosensitivity, drugs with photosensitizing action, and pregnancy).
• other comorbidities such as diabetes and polypharmacy.
• and retraction of the declaration of consent.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Noelia Galiano-Castillo, PhD; 699197690 ext +34; noeliagaliano@ugr.es

• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT05106608
• Other Study ID Numbers: PBM_CANCER21; PI-0187-2021 ( Other Grant/Funding Number: Conserjeria de Salud y Familias (Junta de Andalucía) )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Data will be available upon reasonable request. IPD that underlie the results reported in the future article/s, after deidentification (text, tables, figures, and appendices).
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Researchers who provide a methodologically sound proposal.

• Current Responsible Party: Noelia Galiano-Castillo, Universidad de Granada
• Original Responsible Party: Same as current
• Current Study Sponsor: Universidad de Granada
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Noelia Galiano-Castillo, PhD; Universidad de Granada

• PRS Account: Universidad de Granada
• Verification Date: January 2024