Prevention of Oral Mucositis Using Photobiomodulation Therapy

Study Overview
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Brief Summary
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Oral mucositis is a significant and common toxicity experienced by patients who receive high-dose chemotherapy as a preparatory regimen for a hematopoietic cell transplant (HCT). Furthermore, oral mucositis has been reported as the single most debilitating side effect reported by patients undergoing HCT. The incidence of HCT mucositis among adults is estimated to range between 76% and 89%; however, comparisons are difficult due to variability in patient ages, treatments and criteria for scoring oral mucositis. The use of intra-oral photobiomodulation (PBM) therapy in adult patients after the development of oral mucositis is well documented and now included in the international mucositis guidelines, with limited evidence in pediatrics. This study will build evidence for the incorporation of extra-oral PBM therapy into daily nursing care of children and adolescents undergoing HCT. This intervention has potential in providing evidence for efficacy in the prevention and treatment of oral mucositis, the single most debilitating side effect reported by patients undergoing HCT. Primary Objective: To evaluate feasibility and efficacy of photobiomodulation therapy (PBM) in reducing oral mucositis in children and adolescents at risk for grade 3 oral mucositis undergoing an allogeneic hematopoietic cell transplant (HCT). Secondary Objective: To compare clinical manifestations associated with the development of oral mucositis between those treated with daily PBM and a matched control. Clinical factors to include: grade and duration or oral mucositis. Exploratory Objective: To evaluate efficacy of photobiomodulation therapy in autologous patients at risk for grade 3 oral mucositis compared to matched control. To evaluate utilization of play-based procedural preparation and treatment feasibility and parental satisfaction.

Detailed Description
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Children, adolescents and young adults admitted for an allogeneic HCT and those determined by the transplant team to be at risk for grade 3 oral mucositis will be eligible to receive PBM (34 x 660nm 10mW, 35 x 850nm 30mW: 1390 mW total power output) at an irradiance of 50mW/cm2. The PBM treatment will be administered via the THOR Model LX2M unit. After low light therapy consent, participants will be offered the opportunity to receive a play-based preparation. Those who elect to receive this child life preparation will be scheduled to meet with a trained certified child life specialist (CCL) prior to admission. The play-based preparation will incorporate age and developmentally appropriate explanations of the non-invasive procedure and will be adapted to each patient's psychosocial and cognitive developmental needs. Observation and treatment will begin the first day of conditioning (plus/minus 2 days). Those undergoing an allogeneic HCT will have treatment daily until Day +20 or engraftment (ANC ≥ 500 for two consecutive days). For those undergoing an autologous transplant, treatment will continue until engraftment (ANC ≥ 500 for two consecutive days) or until the patient is without mucositis for two consecutive days. The PBM will be administered extra-oral and intra-oral by trained research staff. Direct aim of the laser into the eye will be avoided and safety spectacles will be used with laser therapy. The safety spectacles will be prescribed according to age, with the adjustable Ibis Infant eye protection for patients less than 1 year of age and the adjustable kids laser safety googles for the young child. Patients, staff, and observers will wear laser safety glasses while PBM is in use. The parent may hold the device in place with assistance from the trained persons. After the initial LLLT treatment, a parent-reported satisfaction survey will be administered via paper questionnaire. The observation of oral mucositis will be conducted by non-study staff and conducted as clinical care by the nurse, advanced practice provider and/or physician. Each patient will have a daily oral assessment, with documentation of mucositis, grade, duration, pain assessment, days of nutrition support, use of narcotics, positive oral and blood cultures. All patients will receive the standard mouth care regimen prescribed for transplant patients. Each patient will be matched and compared to a previously treated patient. The comparison will be matched on primary disease, conditioning regimen, age and sex, with comparison of treatment variables of mucositis grade, duration, pain medications, days of nutritional support, blood and oral cultures, to day +20 or engraftment (depending upon which occurs first).

Official Title
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Prevention of Oral Mucositis in Children and Adolescents Undergoing Hematopoietic Stem Cell Transplant Using Photobiomodulation Therapy

Conditions
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Oral Mucositis

Intervention / Treatment
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* Device: Photobiomodulation Therapy (PBM)
* Other: Pain and Oral Function Assessment
* Other: Parent-Reported Satisfaction Survey


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No age limitation To be admitted for an allogeneic hematopoietic cell transplant All eligible autologous hematopoietic cell transplant, at risk for grade 3 mucositis per transplant service secondary to conditioning regimen or previous history of grade 3 mucositis Dental exam prior to admission, as per preadmission criteria Willingness of research participant to provide assent/consent and parent/ legal guardian/representative to give written informed consent. Exclusion Criteria: Deemed by transplant team as unable to participate Known sensitivity to light therapy Inability or unwillingness of research participant or legal guardian/representative to give written informed consent. CAR-Tcell Protocol
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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Photobiomodulation Therapy (PBM)<br>The PBM will be administered extra-oral and intra-oral. | Device: Photobiomodulation Therapy (PBM)<br>* The PBM will be delivered through application of the LED Cluster Probe externally to the right external buccal, left external buccal, mid face with mouth open and submandibular and left/right cervical. Patients who develop an oral lesion, intra-oral directed therapy will be administered with the dental light probe. For patients that can tolerate, an intraoral probe will deliver light directly onto the oral mucosa, this will then replace the mid face application with mouth open. Each laser application will be timed at 60 seconds.<br>* Other names: PBM therapy;Other: Pain and Oral Function Assessment<br>* After the 6-minute laser/ treatment session the child and parent will complete the mucositis evaluation scale on paper or ipad which includes self-report oral function specific to ability to swallow, eat and drink, as well as the patient's self-reported need for medication specific to mouth pain.<br>* Other names: Mucositis Evaluation Scale;Other: Parent-Reported Satisfaction Survey<br>* A parent-reported satisfaction survey will be administered via paper questionnaire after the initial LLLT treatment. Parent satisfaction will be reported by parents on a 5-point Likert scale to questions adapted from a parent satisfaction survey used in a study regarding child life services in pediatric imaging.<br>* Other names: Survey;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Photo Biomodulation Therapy (PBM) in Reducing Oral Mucositis (OM) in Children and Adolescents at Risk for Grade 3 OM Undergoing an Allogeneic Hematopoietic Cell Transplant (HCT). | Feasibility was assessed through the number of successful treatments (957) administered by the total number of attempted treatments (1023), providing the percentage of successful treatment administered. Daily treatment included 6 sites of PBM application, with application documented as receiving all 6 applications, in part treatment (at least one to five sites) or no treatment. A successful treatment was defined as successfully administered to 4 or more sites. Reasons for partial or no treatment was documented. Criteria for feasibility was 75%. | Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500) | 
| Efficacy of Photo Biomodulation Therapy (PBM) in Reducing Oral Mucositis (OM) in Children and Adolescents at Risk for Grade 3 OM Undergoing an Allogeneic Hematopoietic Cell Transplant (HCT). | It was estimated from a retrospective review of HCT patients that 71% of participants undergoing a HCT developed grade 3 mucositis. With an estimated clinically meaningful effect size of 20% for PBM, the estimated percentage of PBM participant to develop grade 3 mucositis was set at 51%. An interim analysis was conducted after the enrollment of 40 participants. | Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the Severity of Mucositis Grade 1-3 and Duration for Each Patient Treated With PBM Compared to Matched Controls | Patients were ranked according to the severity of their mucositis (a weighted average of mucositis intensity (grade 1-3) by number of days duration) | Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500) | 
| Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control. | Participants treated with PBM therapy were matched to a transplant control who was not treated with PBM. Patients were matched by age, sex, primary disease and transplant conditioning regimen. Total days of grade 1 OM were calculated between PBM treated and untreated | Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500) | 
| Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | Participants treated with PBM therapy were matched to a transplant control who was not treated with PBM. Patients were matched by age, sex, primary disease and transplant conditioning regimen. Total days of grade 1 OM were calculated between PBM treated and untreated. | Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500) | 
| Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | Participants treated with PBM therapy were matched to a transplant control who was not treated with PBM. Patients were matched by age, sex, primary disease and transplant conditioning regimen. Total days of grade 2 OM were calculated between PBM treated and untreated. | Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500) | 
| Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control. | Participants treated with PBM therapy were matched to a transplant control who was not treated with PBM. Patients were matched by age, sex, primary disease and transplant conditioning regimen. Total days of grade 3 OM were calculated between PBM treated and untreated. | Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500) | 
| Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | Participants treated with PBM therapy were matched to a transplant control who was not treated with PBM. Patients were matched by age, sex, primary disease and transplant conditioning regimen. Total days of grade 3 OM were calculated between PBM treated and untreated. | Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500) | 
| Days of Hospitalization Between Groups | Total days of hospitalization between the treated and control group | From the time of admission to discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adolescents, Autologous Transplant, Chemotherapy, Children, Extra-oral Photobiomodulation Therapy, HCT, Hematopoietic Stem Cell Transplant, Low Level Light therapy, Oral Mucositis, PBM, Photobiomodulation Therapy