Ozone Therapy for Oral Mucositis in Patients Receiving Head and Neck Cancer Radio- and Chemotherapy

Oral mucositis is a frequent and painful side effect of radio- and chemotherapy, especially in patients with head and neck cancer. It can cause severe discomfort, difficulty eating and swallowing, infections, and interruptions of cancer treatment. This study evaluates the effectiveness of ozone therapy, delivered both professionally in the dental clinic and at home with ozone-based toothpaste, mouthrinse, and gel, in reducing symptoms of oral mucositis and stomatitis.

Fifty-eight adult cancer patients with oral mucositis of at least WHO grade 1 are included. Professional ozone therapy sessions are performed in-office, combined with daily home use of ozonated products. The main goal is to determine how many days are needed for lesions to heal (WHO ≤ 1). A secondary goal is to measure pain reduction using a visual analogue scale (VAS).

This research aims to provide evidence for a supportive care protocol that may improve quality of life, reduce treatment complications, and support cancer patients during therapy.

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Key information

Conditions

Oral Mucositis Agnosia Chemotherapy Induced Mucositis Head and Neck Cancer Squamous Cell Carcinoma Head and Neck Neoplasms Mouth Diseases Neoplasms Neoplasms by Site Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Oral Stomatitis Pathological Conditions, Signs and Symptoms Perceptual Disorders Radiotherapy Induced Mucositis Signs and Symptoms Stomatitis Stomatognathic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Unit of Orthodontics and Pediatric Dentistry - Section of Dentistry - Department of Clinical, Surgical, Diagnostic and Pediatrics - University of Pavia

Pavia, Lombardy, 27100, Italy

About this study

Oral mucositis and stomatitis are common toxicities in patients receiving radiotherapy, chemotherapy, or combined treatment for cancer, particularly in the head and neck region. These lesions significantly impair oral function, nutrition, and quality of life, and can lead to treatment interruptions and increased risk of infection. Current management options are limited and mainly supportive.

Ozone therapy (O₃) has demonstrated antibacterial, antifungal, antiviral, anti-inflammatory, and analgesic properties. In dentistry and oral medicine, it has been applied to promote mucosal healing, modulate inflammatory responses, and enhance local circulation. This study investigates the combined use of professional in-office ozonotherapy and domiciliary application of ozonated toothpaste, mouthrinse, and gel for the treatment of oral mucositis and/or stomatitis in cancer patients.

Fifty-eight patients are enrolled and followed over multiple time points (baseline to day 15). The primary endpoint is the time to clinical response, defined as improvement to WHO grade ≤ 1. Secondary endpoints include reduction in pain intensity assessed by the Visual Analogue Scale (VAS), as well as exploratory comparisons between patients with head and neck cancers and those with malignancies in other anatomical sites.

The trial is designed as a prospective, interventional, single-arm, open-label study. Statistical analyses will include descriptive statistics, repeated measures ANOVA or non-parametric equivalents, with significance set at p<0.05.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Age ≥ 18 years.
Currently undergoing oncologic therapy (radiotherapy, chemotherapy, or combined treatment).
Presence of oral mucositis or stomatitis of at least WHO grade 1 at baseline evaluation.

Exclusion criteria

Pregnant women.
Patients with Down syndrome.
Patients with epilepsy.
Patients with cardiac pacemakers.
Patients with marked sensitivity to electrical current.
Non-cooperative patients.

Treatment and study plan

Ozone Therapy (In-Office and Home-Based Treatment)

Other

The intervention consists of professional in-office ozone therapy delivered with the Ozono DTA device (Sweden-Martina) applied to oral mucosal lesions. The first treatment is administered at baseline and additional sessions are performed at 48 hours, day 5, day 8, day 12, and day 15, if clinically required. Alongside in-office therapy, participants perform a 15-day domiciliary regimen with ozonated oral care products, including toothpaste with 2% ozonated sunflower oil, a mouthrinse with 4% ozonated sunflower oil solution, and a topical gel with 15% ozonated sunflower oil, each used twice daily. Clinical outcomes are assessed at each visit from baseline to day 15 with the WHO oral mucositis scale and the Visual Analogue Scale for pain.

Primary outcomes

Time to Clinical Response of Oral Mucositis (WHO ≤ 1)

Time frame: Baseline (initial evaluation) (T0); First treatment session (T1); 48 hours (T2; Day 5 (T3); Day 8 (T4); Day 12 (T5); Day 15 (T6).

Clinical response is defined as the first assessment at which oral mucositis improves to WHO grade ≤ 1. Evaluations are performed at baseline (day 0) and during follow-up visits at 48 hours, day 5, day 8, day 12, and day 15. Participants who do not achieve WHO ≤ 1 by day 15 are censored at their last evaluation.

Sponsors and collaborators

Lead sponsor

University of Pavia

Other

Registry information

Official study title

Ozone Therapy for the Treatment of Oral Mucositis and/or Stomatitis in Patients Undergoing Radio- and Chemotherapy in the Head and Neck District: A Prospective Clinical Trial

Acronym: OZOMUC

Important dates

Study start: 2025
Primary completion: 2025
Study completion: 2025
First posted: Sep 30, 2025
Registry last updated: Nov 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed