The Effect of Ozone on Salivary Flow in Patients With Xerostomia and Hyposalivation After Radiotherapy (OZONEXEROSTOMI) (ozonexerostomi)

The Effect of Ozone Therapy on Salivary Flow and Quality of Life in Patients With Xerostomia and Hyposalivation After Head and Neck Radiotherapy

Patients who underwent head and neck radiotherapy and developed xerostomia and/or hyposalivation will be selected. The patients will be randomly assigned into two groups, defined as control and treatment.

All patients will complete the xerostomia-related quality of life questionnaires, XeQoLS (Xerostomia Quality of Life Scale) and OHIP (Oral Health Impact Profile). This qualitative assessment will be repeated 1 week after the 6th application and 1 week after the 12th application (T0, T6, and T12).

The quantitative assessment will be carried out through the collection of unstimulated and stimulated saliva at the same time points (T0, T6, and T12).

Patients will undergo 12 sessions of ozone therapy, once a week, in gaseous form, at a concentration of 10 µg/mL (micrograms per milliliter), applied directly into the major salivary glands.

The gas will be administered as follows:

• Parotid glands: two distinct points per gland, 1 mL at each point.
• Submandibular glands: one point per gland, 1 mL per point at 10 µg/mL.
• Sublingual glands: one point per gland, 1 mL per point at 10 µg/mL. The ozone generator equipment will be supplied with medical oxygen (99.5% purity), Dental model, Philozon company.

Disposable syringes will be Terumo, 10 mL, and the needle will be BD, 30/13 mm.

Study Overview

• Status: Not yet recruiting
• Conditions: Xerostomia Following Radiotherapy
• Intervention / Treatment: Other: Ozone therapy

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sergio B Macedo, PhD; Phone Number: +5561981276050; Email: bruzadelli@unb.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who have undergone head and neck radiotherapy
• Patient who have developed xerostomia
• Patient who have developed hyposalivation

Exclusion Criteria:

• Patients with active malignant disease
• Patients who do not agree to sign the informed consent form

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ozone therapy; Ozone gas will be applied as follows: Parotid glands: two distinct points per gland, 1 mL at each point (10 µg/mL). The anatomical reference will be the parotid region, located anterior and inferior to the external ear.; Submandibular glands: one point per gland, 1 mL at 10 µg/mL. The anatomical reference will be the mandibular base, anterior to the angle, considering its inner aspect.; Sublingual glands: one point per gland, 1 mL at 10 µg/mL. The anatomical reference will be the region of the lower lateral incisor, lingual aspect, punctured through the floor of the mouth mucosa, adjacent to the lingual surface of the mandibular bone. The ozone generator (Dental model, Philozon, Brazil) will be supplied with medical oxygen (99.5% purity).	Other: Ozone therapy; Experimental: Ozone Therapy Ozone gas will be applied as follows: Parotid glands: two distinct points per gland, 1 mL at each point (10 µg/mL). The anatomical reference will be the parotid region, located anterior and inferior to the external ear.; Submandibular glands: one point per gland, 1 mL at 10 µg/mL. The anatomical reference will be the mandibular base, anterior to the angle, considering its inner aspect.; Sublingual glands: one point per gland, 1 mL at 10 µg/mL. The anatomical reference will be the region of the lower lateral incisor, lingual aspect, punctured through the floor of the mouth mucosa, adjacent to the lingual surface of the mandibular bone. The ozone generator (Dental model, Philozon, Brazil) will be supplied with medical oxygen (99.5% purity).
No Intervention: no treatment; Patients in the control group will not receive any treatment but will complete the xerostomia-related quality of life questionnaires and undergo salivary flow assessment at T0, T6, and T12

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Salivary flow	The assessment of unstimulated salivary flow will be conducted according to the technique described by Kogawa et al., 2016. The patient will receive a sterile vial, keep the body slightly leaning forward, place the vial touching the lower lip, and allow saliva to flow into the vial spontaneously for 5 minutes. The unit of measurement will be in microliters.	Time 0 weeks
Salivary flow	The assessment of unstimulated salivary flow will be conducted according to the technique described by Kogawa et al., 2016. The patient will receive a sterile vial, keep the body slightly leaning forward, place the vial touching the lower lip, and allow saliva to flow into the vial spontaneously for 5 minutes. The unit of measurement will be in microliters.	time 6 weeks
Salivary Flow	The assessment of unstimulated salivary flow will be conducted according to the technique described by Kogawa et al., 2016. The patient will receive a sterile vial, keep the body slightly leaning forward, place the vial touching the lower lip, and allow saliva to flow into the vial spontaneously for 5 minutes. The unit of measurement will be in microliters.	12 week
Salivary flow	The assessment of stimulated salivary flow will be conducted according to the technique described by Kogawa et al., 2016. The patient will receive a sterile vial, keep the body slightly leaning forward, place the vial touching the lower lip, and allow saliva to flow into the vial spontaneously for 5 minutes. Stimulated saliva will be collected using the same procedure, preceded by chewing a piece of silicone for 1 minute. The unit of measurement will be in microliters.	Time 0 weeks
Salivary flow	The assessment of stimulated salivary flow will be conducted according to the technique described by Kogawa et al., 2016. The patient will receive a sterile vial, keep the body slightly leaning forward, place the vial touching the lower lip, and allow saliva to flow into the vial spontaneously for 5 minutes. Stimulated saliva will be collected using the same procedure, preceded by chewing a piece of silicone for 1 minute. The unit of measurement will be in microliters.	Time 6 weeks
Salivary flow	The assessment of stimulated salivary flow will be conducted according to the technique described by Kogawa et al., 2016. The patient will receive a sterile vial, keep the body slightly leaning forward, place the vial touching the lower lip, and allow saliva to flow into the vial spontaneously for 5 minutes. Stimulated saliva will be collected using the same procedure, preceded by chewing a piece of silicone for 1 minute. The unit of measurement will be in microliters.	Time 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Xerostomia-Related Quality of Life Scale (XeQoLS)	The Xerostomia-Related Quality of Life Scale (XeQoLS) consists of 15 items, each scored from 0 to 4 according to the severity of xerostomia impact. The final score is calculated as the mean of all items, resulting in a total score ranging from 0 to 4, where 0 indicates no impact and 4 indicates maximum impact. Higher scores indicate worse xerostomia-related quality of life.	time 0 weeks
Xerostomia-Related Quality of Life Scale (XeQoLS)	The Xerostomia-Related Quality of Life Scale (XeQoLS) consists of 15 items, each scored from 0 to 4 according to the severity of xerostomia impact. The final score is calculated as the mean of all items, resulting in a total score ranging from 0 to 4, where 0 indicates no impact and 4 indicates maximum impact. Higher scores indicate worse xerostomia-related quality of life.	time 6 weeks
Xerostomia-Related Quality of Life Scale (XeQoLS)	The Xerostomia-Related Quality of Life Scale (XeQoLS) consists of 15 items, each scored from 0 to 4 according to the severity of xerostomia impact. The final score is calculated as the mean of all items, resulting in a total score ranging from 0 to 4, where 0 indicates no impact and 4 indicates maximum impact. Higher scores indicate worse xerostomia-related quality of life.	time 12 weeks
Oral Health Impact Profile-14 (OHIP-14)	The Oral Health Impact Profile-14 (OHIP-14) is a validated questionnaire consisting of 14 items assessing the impact of oral health on quality of life. Each item is scored from 0 to 4 based on frequency of impact (0 = never, 1 = hardly ever, 2 = occasionally, 3 = fairly often, 4 = very often). The total score is calculated as the sum of all items, ranging from 0 to 56, with higher scores indicating worse oral health-related quality of life.	time 0 weeks
Oral Health Impact Profile-14 (OHIP-14)	The Oral Health Impact Profile-14 (OHIP-14) is a validated questionnaire consisting of 14 items assessing the impact of oral health on quality of life. Each item is scored from 0 to 4 based on frequency of impact (0 = never, 1 = hardly ever, 2 = occasionally, 3 = fairly often, 4 = very often). The total score is calculated as the sum of all items, ranging from 0 to 56, with higher scores indicating worse oral health-related quality of life.	time 6 weeks
Oral Health Impact Profile-14 (OHIP-14)	The Oral Health Impact Profile-14 (OHIP-14) is a validated questionnaire consisting of 14 items assessing the impact of oral health on quality of life. Each item is scored from 0 to 4 based on frequency of impact (0 = never, 1 = hardly ever, 2 = occasionally, 3 = fairly often, 4 = very often). The total score is calculated as the sum of all items, ranging from 0 to 56, with higher scores indicating worse oral health-related quality of life.	time 12 weeks

Collaborators and Investigators

• Sponsor: University of Brasilia

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): July 15, 2027
• Study Completion (Estimated): January 15, 2028

Study Registration Dates

• First Submitted: April 27, 2026
• First Submitted That Met QC Criteria: May 4, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: xerostomia; ozone; hiposalivation; radio therapy
• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases; Xerostomia
• Other Study ID Numbers: 66681722.6.0000.0030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual data will be made available as supplementary material in the final publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No