Combined Gas Ozone Therapy and Biomimetic Oral Care in the Management of Radio- and Chemotherapy-Induced Oral Mucositis: A Randomized Controlled Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Change in Oral Mucositis Severity Assessed by WHO Oral Toxicity Scale
研究概览
简要总结
Oral mucositis is a frequent and often debilitating complication of radiotherapy and chemotherapy, particularly in patients treated for head and neck cancers. It is characterized by inflammation and ulceration of the oral mucosa, leading to pain, difficulty swallowing, taste disturbances, dry mouth, and impairment of daily activities. In more severe cases, oral mucositis may require modification or temporary interruption of cancer treatment.
This randomized controlled clinical trial is designed to assess the clinical effectiveness of gas ozone therapy in patients with radio- and chemotherapy-induced oral mucositis. In addition, the study will evaluate whether combining ozone therapy with a structured biomimetic oral care regimen, including toothpaste and mouthwash, provides additional clinical benefit compared with ozone therapy alone.
Eligible participants will be randomly assigned to one of two parallel groups. The control group will receive gas ozone therapy administered in an outpatient setting according to a standardized protocol. The experimental group will receive the same ozone therapy combined with a defined home oral care regimen. Each participant will be followed for 30 days.
The primary outcome is the change in oral mucositis severity, assessed using the World Health Organization Oral Toxicity Scale. Secondary outcomes include oral pain intensity, salivary flow rates, perceived dry mouth, taste alterations, swallowing function, oral pH, overall oral health-related quality of life, and treatment tolerability.
The findings of this study are expected to clarify the role of ozone-based supportive care strategies in the management of cancer therapy-related oral mucositis and to contribute to the development of standardized non-pharmacological treatment protocols.
详细描述
Oral mucositis represents a clinically relevant toxicity associated with radiotherapy and chemotherapy, particularly in patients undergoing treatment for head and neck malignancies. The condition arises from a multifactorial biological process that includes epithelial injury, inflammatory cascade activation, oxidative stress imbalance, and subsequent disruption of mucosal integrity. The resulting ulcerative lesions are frequently associated with pain, impaired oral intake, dysphagia, taste alterations, and deterioration in oral health-related quality of life. In more severe cases, mucositis may interfere with adherence to oncologic treatment schedules.
Although several supportive approaches have been proposed, there is currently no universally accepted non-pharmacological protocol capable of consistently reducing mucositis severity and improving functional outcomes.
Medical ozone has been investigated in dentistry for its antimicrobial, anti-inflammatory, and tissue-regenerative properties. Experimental evidence suggests that controlled topical ozone exposure may enhance local oxygen metabolism, modulate inflammatory mediators, and promote mucosal repair. However, robust randomized clinical data evaluating standardized gas ozone protocols in patients with cancer therapy-induced oral mucositis remain limited.
The present study is a monocentric, randomized, controlled, parallel-group clinical trial designed to assess the clinical effectiveness of gas ozone therapy administered using a certified medical device. The trial also aims to investigate whether the association of ozone therapy with a structured biomimetic oral care regimen provides additional benefit compared with ozone therapy alone.
Eligible participants diagnosed with grade 1-3 oral mucositis will be randomized in a 1:1 ratio to receive either ozone therapy alone or ozone therapy combined with a defined home oral care protocol. Ozone applications will be performed in an outpatient clinical setting according to standardized parameters over a 30-day period. Participants allocated to the combined treatment arm will follow a structured domiciliary oral hygiene regimen throughout the study duration.
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
- Single (Outcomes Assessor)
盲法说明
The investigator responsible for outcome assessment is blinded to treatment allocation. The operator responsible for treatment allocation and intervention delivery is not blinded.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Confirmed diagnosis of radio- and/or chemotherapy-induced oral mucositis, grade 1-3 according to the WHO Oral Toxicity Scale
- •Undergoing oncologic treatment for solid malignancies, particularly head and neck cancers
- •Clinically stable general health condition (ASA physical status I-III)
- •Ability to understand and comply with study procedures, including domiciliary treatment and questionnaire completion
- •Written informed consent provided
排除标准
- •Oral mucositis grade 4 according to the WHO Oral Toxicity Scale
- •Active fungal or bacterial oral infections (e.g., candidiasis, ulcerative stomatitis)
- •Traumatic ulcers, non-oncologic mucositis, or concomitant oral mucosal diseases (e.g., lichen planus, pemphigus, graft-versus-host disease)
- •Ongoing head and neck radiotherapy with cumulative dose >70 Gy or completion within 7 days prior to enrollment
- •Use within 14 days prior to enrollment of mouthwashes, sprays, or gels containing hyaluronic acid, ozone, aloe vera, or similar bioactive agents
- •Systemic or topical therapies known to interfere with salivary function or mucosal healing (e.g., anticholinergics, tricyclic antidepressants, diuretics)
- •Known allergy or hypersensitivity to components of the oral care products or materials used during ozone therapy
- •Severe or uncontrolled systemic diseases (including hepatic, renal, respiratory, or cardiac insufficiency)
- •Severe immunosuppression or neutropenia (neutrophils <1,000/mm³)
- •Pregnancy or breastfeeding
- •Alcohol or substance abuse, or any condition that may compromise adherence to the protocol
- •Inability to attend scheduled follow-up visits through Day 30
结局指标
主要结局
Change in Oral Mucositis Severity Assessed by WHO Oral Toxicity Scale
时间窗: Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)
The primary outcome is the change in oral mucositis severity measured using the World Health Organization (WHO) Oral Toxicity Scale. The scale ranges from 0 (no mucositis) to 4 (severe mucositis preventing oral intake), with higher scores indicating greater mucosal damage severity. Changes in WHO grade from baseline will be compared between study groups to evaluate the clinical effectiveness of the interventions.
次要结局
- Change in Oral Pain Intensity Assessed by Visual Analogue Scale (VAS)(Baseline (T0), end of first treatment session (T1), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4))
- Change in Unstimulated Salivary Flow Rate (UWS)(Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4))
- Change in Stimulated Salivary Flow Rate (SWS)(Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4))
- Change in Xerostomia Severity Assessed by Xerostomia Inventory-11 (XI-11)(Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4))
- Change in Taste Alterations Assessed by Chemotherapy-Induced Taste Alteration Scale (CiTAS)(Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4))
- Change in Swallowing-Related Quality of Life Assessed by MDADI(Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4))
- Change in Functional Oral Intake Assessed by FOIS(Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4))
- Change in Oral Health-Related Quality of Life Assessed by OHIP-14(Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4))
- Patient's Global Impression of Change (PGIC)(7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4))
- Change in Oral pH(Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4))
研究者
Andrea Scribante
Associate Professor, Principal Investigator
University of Pavia