Ozone Therapy With Biomimetic Oral Care for Cancer-Related Oral Mucositis
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Pavia
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Gas Ozone Therapy
DeviceMedical 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.
Biomimetic Oral Care Regimen
Other interventionParticipants 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.
Treatment groups
50 Participants
are divided into 2 treatment groupsGroup A: Gas Ozone TherapyActive comparator 1 intervention
Group B: Gas Ozone Therapy Plus Biomimetic Oral CareExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Change in Oral Mucositis Severity Assessed by WHO Oral Toxicity Scale
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.
Time frame
Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)Secondary outcomes
1
Change in Oral Pain Intensity Assessed by Visual Analogue Scale (VAS)
Oral pain intensity will be measured using a 100-mm Visual Analogue Scale (VAS), ranging from 0 (no pain) to 100 (worst imaginable pain). Higher scores indicate greater pain intensity. Changes in VAS scores over time will be compared between study groups to assess treatment-related differences in symptom reduction.
Time frame
Baseline (T0), end of first treatment session (T1), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)2
Change in Unstimulated Salivary Flow Rate (UWS)
Salivary flow will be quantified by measuring unstimulated whole saliva (UWS), expressed in mL/min, with values ranging from 0 to theoretically unlimited positive values depending on salivary output. Lower values indicate reduced salivary gland function. Measurements will be performed under standardized conditions to evaluate changes in salivary gland function over time.
Time frame
Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)3
Change in Stimulated Salivary Flow Rate (SWS)
Salivary flow will be quantified by measuring stimulated whole saliva (SWS), expressed in mL/min, with values ranging from 0 to theoretically unlimited positive values depending on salivary output. Lower values indicate reduced salivary gland function. Measurements will be performed under standardized conditions to evaluate changes in salivary gland function over time. SWS will be collected following gustatory stimulation using fresh lemon juice (approximately two drops, \~0.1 mL, applied to the dorsal surface of the tongue).
Time frame
Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)4
Change in Xerostomia Severity Assessed by Xerostomia Inventory-11 (XI-11)
Subjective xerostomia will be assessed using the Xerostomia Inventory-11 (XI-11), an 11-item questionnaire scored on a 5-point Likert scale. The total score ranges from 11 to 55, with higher scores indicating greater perceived dry mouth severity.
Time frame
Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)Sponsors and contacts
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Source ClinicalTrials.gov