Ozone Therapy With Biomimetic Oral Care for Cancer-Related Oral Mucositis
Combined Gas Ozone Therapy and Biomimetic Oral Care in the Management of Radio- and Chemotherapy-Induced Oral Mucositis: A Randomized Controlled Clinical Trial
University of Pavia
50 participants
Mar 1, 2026
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria6
- 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
Exclusion Criteria12
- 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
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Interventions
Medical gas ozone will be administered in an outpatient clinical setting using a certified ozone delivery system. Prior to application, the affected oral mucosal areas will be gently dried. Ozone will be applied locally using a dedicated silicone applicator, with an exposure time of 60 seconds per cm² and a maximum of four sites treated per session at predefined device settings. Treatment sessions will be performed three times weekly during the first two weeks (days 1, 3, and 5), followed by twice-weekly sessions until day 30. All participants will receive standardized oral hygiene instructions and will use the same biomimetic toothpaste throughout the study period.
Participants allocated to the experimental arm will use a biomimetic mouthwash in addition to the standardized gas ozone therapy protocol. The mouthwash will be applied twice daily, in the morning and evening, after routine oral hygiene procedures for 30 consecutive days. Adherence to the domiciliary regimen will be monitored using a structured patient diary.
Locations(1)
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NCT07491536