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Oral MucositisOZOMUCNCT07491536

Ozone Therapy With Biomimetic Oral Care for Cancer-Related Oral Mucositis

A study testing Gas Ozone Therapy and Biomimetic Oral Care Regimen in people with Oral Mucositis and Chemotherapy-induced Oral Mucositis, run by University of Pavia at 1 site in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Gas Ozone Therapy and Biomimetic Oral Care Regimen
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteItaly
Study dates
1 Mar 2026to 15 Dec 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 12Show fewer
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Andrea Scribante, Associate Professor contact

+39 0382516223

andrea.scribante@unipv.it

Italy1 site, 1 recruiting
  • Unit of Orthodontics and Pediatric Dentistry - Section of Dentistry - Department of Clinical, Surgical, Diagnostic and Pediatrics - University of Pavia

    Pavia, Lombardy, 27100

    Andrea Scribante, Associate Professor, +39 0382516223, andrea.scribante@unipv.it

    Recruiting

Other trials in Italy

About this study

Official title: Combined Gas Ozone Therapy and Biomimetic Oral Care in the Management of Radio- and Chemotherapy-Induced Oral Mucositis: A Randomized Controlled Clinical 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.

Read more

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.

Read the detailed description

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.

Being tested
Gas Ozone Therapy, Biomimetic Oral Care Regimen
Keywords
Ozone Therapy, Cancer Treatment-Induced Oral Mucositis, Supportive Oncology, Non-Pharmacological Treatment, Head and Neck Cancer, Oral Toxicity, Salivary Function, Xerostomia, Randomized Controlled Trial
Medical subject headings
Stomatitis, Head and Neck Neoplasms, Xerostomia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Gas Ozone TherapyDevice

    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.

  • Biomimetic Oral Care RegimenOther

    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.

Study groups in NCT07491536
Study groupRoleWhat they receive
Gas Ozone TherapyActive comparatorParticipants 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.
Receives: Device: Gas Ozone Therapy
Gas Ozone Therapy Plus Biomimetic Oral CareExperimentalParticipants 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.
Receives: Other: Biomimetic Oral Care Regimen

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)

Secondary outcomes (10)
  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.

    Measured: 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.

    Measured: 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).

    Measured: 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.

    Measured: Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)

  5. 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.

    Measured: Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)

  6. 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.

    Measured: Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)

  7. 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.

    Measured: Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)

  8. 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.

    Measured: Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)

  9. 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.

    Measured: 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)

  10. 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.

    Measured: Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Mar 2026
  2. Study start1 Mar 2026 (estimated)
  3. Primary completion1 Dec 2026 (estimated)
  4. Study completion15 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07491536
Sponsor's protocol ID
2026-OZONEOM
Acronym
OZOMUC
Status last verified
Mar 2026
First submitted
25 Feb 2026
Last updated
24 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Data will be available upon motivated request to the corresponding authors.

Questions about this trial

What is this clinical trial studying?

A study testing Gas Ozone Therapy and Biomimetic Oral Care Regimen in people with Oral Mucositis and Chemotherapy-induced Oral Mucositis, run by University of Pavia at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Andrea Scribante, Associate Professor (+39 0382516223, andrea.scribante@unipv.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Oral Mucositis Severity Assessed by WHO Oral Toxicity Scale (time frame: Baseline (T0), 7-day follow-up (T2), 15-day follow-up (T3), and 30-day follow-up (T4)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2026.

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