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

NCT07491536 | Recruiting

• 1 other identifier: 2026-OZONEOM
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Oral Mucositis; Chemotherapy-induced Oral Mucositis; Head and Neck Neoplasms

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

Outcome Measures

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.

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

Secondary Outcomes (10)

• Change in Oral Pain Intensity Assessed by Visual Analogue Scale (VAS)

  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)

  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)

  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)

  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)

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

Study Arms (2)

Gas Ozone Therapy

ACTIVE COMPARATOR

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

Gas Ozone Therapy Plus Biomimetic Oral Care

EXPERIMENTAL

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

Interventions

Gas Ozone Therapy DEVICE

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.

Gas Ozone Therapy

Biomimetic Oral Care Regimen OTHER

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.

Gas Ozone Therapy Plus Biomimetic Oral Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• University of Pavia: lead

Study Sites (1)

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

Pavia, Lombardy, 27100, Italy

RECRUITING

MeSH Terms

Conditions

Stomatitis; Head and Neck Neoplasms; Xerostomia

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Salivary Gland Diseases

Study Officials

• Andrea Scribante, Associate Professor

  University of Pavia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Scribante, Associate Professor

CONTACT

+39 0382516223; andrea.scribante@unipv.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The investigator responsible for outcome assessment is blinded to treatment allocation. The operator responsible for treatment allocation and intervention delivery is not blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Principal Investigator

Study Record Dates

• First Submitted: February 25, 2026
• First Posted: March 24, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)