Aerosolized Mesenchymal Stem Cell-Derived Exosomes for the Prevention and Treatment of Radiation-Induced Oral Mucositis: A Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- The incidence of grade ≥3 radiation-induced oral mucositis
研究概览
简要总结
Radiation-induced oral mucositis (RIOM) is an inevitable acute complication in radiotherapy for head and neck malignancies, characterized by a complex pathogenesis involving multiple biological processes. According to the latest data from the International Agency for Research on Cancer (IARC), approximately 650,000 new cases of head and neck cancers are diagnosed globally each year, with about 70% of patients undergoing radiotherapy. RIOM develops through a multistep pathophysiological cascade, including initiation of mucosal injury, signaling amplification, inflammatory response, ulceration, and eventual healing. Ionizing radiation induces DNA damage in oral mucosal epithelial cells, triggering increased apoptosis. This cellular injury promotes the activation and release of pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), compromising the integrity of the mucosal barrier and ultimately leading to ulcer formation. Current clinical management of RIOM remains largely supportive, relying on oral hygiene, nutritional supplementation, and pain control, with no effective prophylactic agents available. Despite extensive research into potential interventions internationally, no drugs specifically approved by the FDA or NMPA for the prevention of RIOM have reached the market. This significant unmet clinical need calls for urgent scientific and therapeutic advancement. This study aims to evaluate the therapeutic efficacy and safety profile of aerosolized exosomes derived from mesenchymal stem cells in the prevention and treatment of radiation-induced oral mucositis in patients receiving radiotherapy for head and neck cancers. The ultimate objective is to establish a novel and effective therapeutic strategy for clinical application.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This study adopted an open-label design, meaning that both the investigators and the participants are aware of the treatment group assignments. The investigational and control medications were not processed for blinding purposes and were routinely provided and used in their standard forms.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
experimental group
mesenchymal stem cell-derived exosomes. Administer the mesenchymal exosome spray three times daily-30 minutes after each main meal (breakfast, lunch, and dinner)-with a dosage of approximately 1.5 mL per application. Initiation of the study drug on the first day of radiotherapy and continuing through the completion of the treatment course.
干预措施: mesenchymal stem cell-derived exosomes (Drug)
结局指标
主要结局
The incidence of grade ≥3 radiation-induced oral mucositis
时间窗: Within 90 days from the initiation to the completion of radiotherapy
The primary endpoint is defined as the proportion of patients who develop grade 3 or higher radiation-induced oral mucositis (RIOM) from the start of radiotherapy until 90 days after the completion of radiotherapy. RIOM was graded according to the WHO oral toxicity scale criteria: Grade 0: No changes in the oral mucosa; Grade 1: Erythema of the oral mucosa with mild pain, not requiring analgesics; Grade 2: Patchy mucositis with serous exudate, moderate pain, usually not requiring analgesics; Grade 3: Confluent mucositis with severe pain requiring analgesics; Grade 4: Ulceration, hemorrhage, or necrosis, with intense pain affecting oral intake.
次要结局
- Incidence rate of RIOM at any level(Within 90 days from the initiation to the completion of radiotherapy)