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

Mucositis Oral Clinical Trial

— CURALASE01  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04596410
• Other study ID #: RC31/19/0556
• Status: Recruiting
• Phase: N/A
• Start date: May 3, 2021
• Est. completion date: February 2024

Study information

• Verified date: September 2023
• Source: University Hospital, Toulouse
• Contact: Marlène PASQUET, MD
• Phone: 05 34 55 86 43
• Email: pasquet.m[@]chu-toulouse.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 406
• Est. completion date: February 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Mucositis
• Mucositis Oral
• Stomatitis

Intervention

Radiation:
• LLLT applied every other day
Low-level laser therapy (LLLT) protocol combining red and infrared wavelengths applied every other day
• LLLT applied daily
Low-level laser therapy (LLLT) protocol combining red and infrared wavelengths applied daily

Locations

Country	Name	City	State
France	University hospital of Angers	Angers
France	University hospital of Besançon	Besançon
France	University hospital of Grenoble	Grenoble
France	University hospital of Lille	Lille
France	University hospital of Limoges	Limoges
France	Hôpital La Timone	Marseille
France	University hospital of Nancy	Nancy
France	University Hospital of Nice	Nice
France	Armand Trousseau Hospital	Paris
France	University hospital of Poitiers	Poitiers
France	University hospital of Reims	Reims
France	University hospital of Rouen	Rouen
France	University hospital of Saint-Etienne	Saint-Étienne
France	University hospital of Strasbourg	Strasbourg
France	University hospital of Toulouse	Toulouse	Occitanie
France	University Hospital of Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Health insurance evaluation	Costs of inpatient hospital stays from the French health insurance perspective.	2 months
Secondary	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
Secondary	OM occurrence	Occurrence of chemotherapy-induced OM of WHO grade 3 or 4 (deterioration of the clinical situation).	2 months
Secondary	Feed evaluation	Occurrence of enteral feeding.	2 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Adverse events occurrence	Occurrence of adverse events reported according to descriptions and grading scale found in NCI CTCAE version 5.0.	2 months
Secondary	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