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

NCT ID: NCT07199712

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-01
• Study Completion Date: 2025-11-20

Brief Summary

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.

Detailed Description

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.

Conditions

Oral Mucositis; Oral Stomatitis; Head and Neck Cancer Squamous Cell Carcinoma; Radiotherapy Induced Mucositis; Chemotherapy Induced Mucositis

Keywords

Ozone Therapy; Oral Mucositis; Head and Neck Cancer; Chemotherapy-Induced Mucositis; Radiotherapy-Induced Mucositis; Supportive Care; Pain Management; WHO Oral Toxicity Scale; Visual Analogue Scale (VAS)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Ozonotherapy Protocol (Professional and Home-Based)

All participants receive professional in-office ozone therapy with the Ozono DTA device (Sweden-Martina). The first treatment is administered at baseline (T0/T1), followed by additional applications at 48 hours (T2), day 5 (T3), day 8 (T4), day 12 (T5), and day 15 (T6), if clinically indicated. In parallel, participants perform domiciliary treatment for the entire 15-day study period, consisting of daily use of an ozonated toothpaste (DentoO3, 2% ozonated sunflower oil), an ozonated mouthrinse (CollutO3, 4% ozonated sunflower oil solution), and a topical ozonated gel (Ozoral Gel, 15% ozonated sunflower oil), each applied twice daily. Clinical assessments with the WHO oral mucositis scale and the Visual Analogue Scale for pain are performed at all study visits from baseline to day 15.

Group Type: EXPERIMENTAL

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

Intervention Type: 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.

Interventions

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

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.

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pavia

OTHER

Sponsor Role: lead

Responsible Party

Andrea Scribante

Associate Professor, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrea Scribante, Associate Professor

Role: PRINCIPAL_INVESTIGATOR

University of Pavia

Locations

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

Pavia, Lombardy, Italy

Countries

Italy

Central Contacts

Andrea Scribante, Associate Professor

Role: CONTACT

Phone: +39 0382516223

Email: andrea.scribante@unipv.it

Facility Contacts

Andrea Scribante, Associate Professor

Role: primary

Other Identifiers

2025-OMUC-O3

Identifier Type: -

Identifier Source: org_study_id