An interventional study of Gas Ozone Therapy and Biomimetic Oral Care Regimen in Oral Mucositis, Chemotherapy-induced Oral Mucositis and Head and Neck Neoplasms, sponsored by University of Pavia. Recruiting at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-24.
Sponsored by University of Pavia · Not applicable, Interventional, and Treatment
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.
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.
Clinical evaluations and patient-reported outcome measures will be collected at predefined follow-up visits to monitor mucosal status, symptom progression, functional changes, and treatment tolerability. The study is designed to generate clinically applicable data regarding the role of ozone-based supportive care strategies in the management of radio- and chemotherapy-induced oral mucositis.
306 studies on the registry are indexed under Stomatitis; 75 are open to participants now.
This study's planned enrollment of 50 is below the median of 60 across 276 interventional studies indexed under Stomatitis.
Browse Stomatitis studies →University of Pavia is the lead sponsor of 144 studies on the registry; 39 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ASA physical status
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants assigned to this arm will receive gas ozone therapy administered in an outpatient clinical setting using a certified medical device. The oral mucosa will be gently dried prior to treatment, and ozone will be applied locally to affected areas using a dedicated silicone applicator. Each site will receive 60 seconds of exposure per cm² at predefined device settings, with a maximum of four sites treated per session. Treatment 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.
Device: Gas Ozone Therapy
Participants assigned to this arm will receive the same standardized gas ozone therapy protocol described for the control group. In addition, they will use a biomimetic mouthwash twice daily (morning and evening) after routine oral hygiene procedures for 30 consecutive days. All participants will receive standardized oral hygiene instructions and will use the same biomimetic toothpaste during the study period. Adherence to the domiciliary mouthwash regimen will be monitored through a structured patient diary.
Other: Biomimetic Oral Care Regimen
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.
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)
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)
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)
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)
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)
Change in Taste Alterations Assessed by Chemotherapy-Induced Taste Alteration Scale (CiTAS)
Taste disturbances will be evaluated using the Chemotherapy-Induced Taste Alteration Scale (CiTAS), an 18-item questionnaire with each item scored from 1 to 5. The total score ranges from 18 to 90, with higher scores indicating greater taste impairment.
Time frame: 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
Swallowing-related quality of life will be assessed using the M.D. Anderson Dysphagia Inventory (MDADI). The composite score ranges from 20 to 100, with higher scores indicating better swallowing-related quality of life. Changes in MDADI scores over time will be analyzed between study groups.
Time frame: 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
Functional oral intake will be evaluated using the Functional Oral Intake Scale (FOIS), which ranges from 1 (no oral intake) to 7 (full oral intake without restrictions). Higher scores indicate better functional oral intake.
Time frame: 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
Oral health-related quality of life will be measured using the 14-item Oral Health Impact Profile (OHIP-14). Total scores range from 0 to 56, with higher scores indicating worse oral health-related quality of life.
Time frame: 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)
Global patient-perceived improvement will be assessed using the 7-point Patient's Global Impression of Change (PGIC) scale, ranging from 1 (very much improved) to 7 (very much worse). Lower scores indicate greater perceived improvement.
Time frame: 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)
Change in Oral pH
Oral pH will be measured using standardized pH indicator strips. The pH scale ranges from 0 to 14, where lower values indicate higher acidity, 7 indicates neutrality, and higher values indicate alkalinity. Changes in oral pH over time will be evaluated between study groups.
Time frame: Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)
Plan to share: No — Data will be available upon motivated request to the corresponding authors.
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