Aerosolized Mesenchymal Stem Cell-Derived Exosomes for the Prevention and Treatment of Radiation-Induced Oral Mucositis

This study employs a randomized controlled design, aiming to enroll a total of 200 head and neck cancer patients scheduled to undergo radiotherapy from three medical centers. The experimental group (100 patients) will receive a mesenchymal stem cell-derived exosome spray, while the control group (100 patients) will follow a placebo-controlled design without any pharmacological intervention, receiving only standard radiotherapy and supportive care. The primary endpoint is the incidence of grade 3 or higher radiation-induced oral mucositis, which will be used to evaluate the efficacy of the investigational agent in preventing and ameliorating this condition through comparison with the control group.

Inclusion criteria

• Histologically or cytologically confirmed malignant tumor of the head and neck;
• Age 18-75 years;
• Scheduled to receive radical radiotherapy with a total planned dose of ≥60 Gy, with radiation fields including the oral cavity and/or oropharynx;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 and a life expectancy of ≥6 months.
• White blood cell≥3.0×10^9/L, hemoglobin≥ 90 g/L, platelet (PLT)≥ 100x10^9/ L
• Transaminases≤2.5 times the upper limit of normal, total bilirubin ≤1.5 times the upper limit of normal;
• Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min;
• Cardiac: Electrocardiogram (ECG) without clinically significant abnormalities;
• Intact oral mucosa before initiation of radiotherapy. Absence of active oral infections or severe periodontal disease before initiation of radiotherapy;
• Signed informed consent form.

Exclusion criteria

• Previous radiotherapy to the head and neck region;
• Head and neck surgery within the preceding 4 weeks;
• Current participation in another clinical trial, or participation in another interventional study within the past 4 weeks;
• Significant cardiovascular disease, including unstable angina, myocardial infarction within the past 6 months, severe arrhythmia, or heart failure (NYHA Class III-IV);
• Severe hepatic or renal dysfunction, such as cirrhosis or chronic renal insufficiency (creatinine clearance <30 mL/min);
• Active systemic infection requiring antimicrobial therapy;
• Autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis) requiring ongoing immunosuppressive treatment;
• Severe psychiatric disorders that may impair the ability to provide informed consent or adhere to the study protocol;
• Using other oral mucosal protective agents or anti-inflammatory medications that cannot be discontinued. Long-term use of immunosuppressants or corticosteroids at a prednisone-equivalent dose >10 mg/day;
• Individuals unable to comprehend the study requirements or comply with study procedures;
• Any other condition that, in the judgment of the investigator, would render the patient unsuitable for participation in the study.