Photobiomodulation Protocols in the Analgesia of Chemotherapy-induced Oral Mucositis in Children (CURALASE01)

Double-blind, Randomized, Multi-center, Non-inferiority Clinical Trial Comparing Two Photobiomodulation Protocols in the Analgesia of Chemotherapy-induced Oral Mucositis in Children

Chemotherapy-induced oropharyngeal mucositis (OM) negatively impacts the quality of life of adult and pediatric patients by causing pain, dysphagia, dysgeusia and dysphonia.

Photobiomodulation (PBM) by low level laser therapy (LLLT), light therapy of low level of red and infrared wavelengths (630-1000 nm) has been recommended since 2014 in patients treated with high-dose chemotherapy for bone marrow transplantation. Available pediatric studies highlighted positive/promising results of PBM with excellent safety and no adverse effects. Nevertheless, a wide variety of application parameters is described in the literature, with no consensus guidelines.

Considering the lack of standardized protocol of photobiomodulation in the pediatric population as well as the burden and cost of a daily application, investigators have decided to conduct, for the first time in children of 3 years of age or older, a multicenter, randomized, double-blind, non-inferiority clinical trial to compare two PBM protocols with same PBM parameters, combining red and infrared wavelengths, but with different frequencies of laser application (daily versus every other day), in the treatment of chemotherapy-induced OM of WHO grade 2 or higher.

Study Overview

• Status: Recruiting
• Conditions: Mucositis Oral
• Intervention / Treatment: Radiation: LLLT applied every other day; Radiation: LLLT applied daily

• Study Type: Interventional
• Enrollment (Estimated): 406
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marlène PASQUET, MD; Phone Number: +33 05 34 55 86 43; Email: pasquet.m@chu-toulouse.fr
• Study Contact Backup: Name: Gwennaëlle ALPHONSA, CRA; Phone Number: +33 05 67 77 13 94; Email: alphonsa.g@chu-toulouse.fr

Study Locations

• France
  • Angers, France
    • Recruiting
    • University Hospital of Angers
    • Contact: Isabelle PELLIER, MD
    • Principal Investigator: Isabelle PELLIER, MD
  • Besançon, France
    • Recruiting
    • University Hospital of Besancon
    • Contact: Sebastien KLEIN, MD
    • Principal Investigator: Sebastien KLEIN
  • Grenoble, France
    • Recruiting
    • University hospital of Grenoble
    • Principal Investigator: Dominique PLANTAZ
    • Contact: Dominique PLANTAZ, MD
  • Lille, France
    • Recruiting
    • University Hospital of Lille
    • Contact: Wadih ABOU CHAHLA, MD
    • Principal Investigator: Wadih ABOU CHAHLA, MD
  • Limoges, France
    • Recruiting
    • University Hospital of Limoges
    • Principal Investigator: Caroline OUDOT, MD
    • Contact: Caroline Oudot, MD
  • Marseille, France
    • Recruiting
    • Hôpital La Timone
    • Contact: Arthur STERIN, MD
    • Principal Investigator: Arthur STERIN, MD
  • Nancy, France
    • Recruiting
    • University Hospital Of Nancy
    • Contact: Julie VALDUGA, MD
    • Principal Investigator: Julie VALDUGA, MD
  • Nice, France
    • Recruiting
    • University Hospital of Nice
    • Contact: Marilyne POIREE, MD
    • Principal Investigator: Marilyne POIREE, MD
  • Paris, France
    • Recruiting
    • Armand Trousseau Hospital
    • Contact: Catherine DOLLFUS, MD
    • Principal Investigator: Catherine DOLLFUS, MD
  • Poitiers, France
    • Recruiting
    • University Hospital of Poitiers
    • Contact: Chrystelle DUPRAZ, MD
    • Principal Investigator: Chrystelle DUPRAZ, MD
  • Reims, France
    • Recruiting
    • University Hospital of Reims
    • Contact: Claire PLUCHART, MD
    • Principal Investigator: Claire Pluchart, MD
  • Rouen, France
    • Recruiting
    • University Hospital of Rouen
    • Contact: Marie, MD
    • Principal Investigator: Marie JAFFRAY, MD
  • Saint-Étienne, France
    • Recruiting
    • University Hospital of Saint-Etienne
    • Contact: Sandrine THOUVENIN -DOULET, MD
    • Principal Investigator: Sandrine THOUVENIN -DOULET, MD
  • Strasbourg, France
    • Recruiting
    • University Hospital of Strasbourg
    • Contact: Catherine PAILLARD, MD
    • Principal Investigator: Catherine PAILLARD, MD
  • Tours, France
    • Recruiting
    • University Hospital of Tours
    • Contact: Julien, MD
    • Principal Investigator: Julien LEJEUNE, MD
  • Occitanie
    • Toulouse, Occitanie, France, 31000
      • Recruiting
      • University Hospital of Toulouse
      • Contact: Gwennaëlle ALPHONSA, CRA; Phone Number: +33 05 67 77 13 94; Email: alphonsa.g@chu-toulouse.fr
      • Contact: Marlène PASQUET, MD; Phone Number: +33 0534558643; Email: pasquet.m@chu-toulouse.fr
      • Principal Investigator: Cécile BOULANGER, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female children aged ≥ 3 years and < 18 years.
2. Hospitalization in an oncology or hematology department in the participating centres.
3. Patients with oropharyngeal mucositis of grade 2 or higher (WHO grading system) related to cancer chemotherapy, including conditioning for Hematopoietic Stem Cell Transplantation (HSCT).
4. Written informed consent of both patient's holders of parental authority, and patient's assent when applicable.
5. Patients affiliated to a French Social Security insurance or equivalent social protection.
6. Absence of any physical or psychological disability that may interfere with the LLLT application.

Exclusion Criteria:

1. Patients with a solid cancer lesion in the area of low-level laser application.
2. History of cervicofacial radiotherapy.
3. Application of low-level laser therapy for oral mucositis within 2 weeks prior to randomization.
4. Hyperthyroidism defined by TSH < 0.4 IU/mL at inclusion.
5. Patients susceptible to epilepsy seizure.
6. Patients with pacemaker.
7. Patients refusing to wear retinal goggles during low-level laser 1. Patients with a solid cancer lesion in the area of low-level laser application.
8. Patients protected by law (guardianship and safeguarding of justice).
9. Pregnant female patients as determined by positive serum pregnancy test at screening.
10. Lactating female patients who are actively breast feeding.
11. Participation in another clinical trial involving oral care.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LLLT applied every other day; Low-level laser therapy (LLLT) protocol combining red and infrared wavelengths applied every other day	Radiation: LLLT applied every other day; Low-level laser therapy (LLLT) protocol combining red and infrared wavelengths applied every other day
Active Comparator: LLLT applied daily; Low-level laser therapy (LLLT) protocol combining red and infrared wavelengths applied every day	Radiation: LLLT applied daily; Low-level laser therapy (LLLT) protocol combining red and infrared wavelengths applied daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Session evaluation	Duration (in days) from the day of first PBM session up to the day of first measurement when patient has no longer WHO grade 2 or higher chemotherapy-induced OM related pain at 2 consecutive measurements before the next scheduled PBM session (either active laser application or matching placebo application)	Throught treatment period up to 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Production costs evaluation	Production costs from the hospital perspective and efficacy (i.e. number of days after which a child has no longer mucositis related pain as described in the primary endpoint section) to build Incremental Cost-Effectiveness Ratio (ICER) comparing every other day LLLT application versus with daily LLLT application.	2 months
Health insurance evaluation	Costs of inpatient hospital stays from the French health insurance perspective.	2 months
OM duration evaluation	Duration (in days) of chemotherapy-induced OM of WHO grade 2 or higher between the day of first PBM session up to the day of first measurement when patient has no longer WHO grade 2 or higher chemotherapy-induced OM at 2 consecutive measurements before the next scheduled PBM session (either every other day application or daily application).	Throught treatment period up to 1 month
OM occurrence	Occurrence of chemotherapy-induced OM of WHO grade 3 or 4 (deterioration of the clinical situation).	2 months
Feed evaluation	Occurrence of enteral feeding.	2 months
Analgesic consumption	Duration (in days) of consumption of step 2 and step 3 analgesics during chemotherapy-induced OM of WHO grade 2 or higher.	2 months
PBM evaluation	Duration (in days) from the day of first PBM session up to the day of first measurement when patient has no longer WHO grade 2 or higher chemotherapy-induced OM related pain at 2 consecutive measurements before the next scheduled PBM session (either active laser application or matching placebo application) as evaluated, regardless of patient's age, with the ChIMES scale and use of step 3 analgesics.	Through treatment period up to 1 month
Pain change evaluation	Change over time in WHO grade 2 or higher chemotherapy-induced OM related pain, as assessed by pain scales (HEDEN (Hétero Evaluation Douleur Enfant) mucositis scale (5 items ranging from 0 to 2) or VAS (ranging from 0 to 10)depending on patient's age category, and Children's International Mucositis Evaluation Scale (4 items ranging from 0 to 5) whatever patient's age category)	From baseline to each day of PBM session
Adverse events occurrence	Occurrence of adverse events reported according to descriptions and grading scale found in NCI CTCAE version 5.0.	2 months
thyroid-stimulating hormone (TSH) evolution	TSH shift from baseline value classified according to the following three categories: "< 0.4 IU/mL", "[0.4 - 10] IU/mL", "> 10 IU/mL", to value at D14-31 after end of WHO grade 2 or higher chemotherapy-induced OM classified according to the same three categories.	From baseline to 2 months

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Marlène PASQUET, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2021
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): February 1, 2024

Study Registration Dates

• First Submitted: September 4, 2020
• First Submitted That Met QC Criteria: October 15, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Children; Chemotherapy; Oral mucositis; Photobiomodulation
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Mucositis; Stomatitis
• Other Study ID Numbers: RC31/19/0556

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No