A Lithium-containing Mouthwash Prevention and Treatment of Oral Mucositis and Dysgeusia in Patients Undergoing Radiotherapy

To evaluate the efficacy and safety of lithium-containing mouthwash for prevention and treatment of oral mucositis and dysgeusia in patients undergoing radiotherapy for malignant head and neck tumors.

Study Overview

• Status: Completed
• Conditions: Head and Neck Squamous Cell Carcinoma; Malignant Head and Neck Tumors
• Intervention / Treatment: Drug: lithium-containing mouthwash; Drug: Plcacebo mouthwash; Drug: lithium-containing mouthwash

Detailed Description

The goal of this clinical trial is to evaluate the efficacy and safety of lithium-containing mouthwash in reducing the incidence, duration, and severity of severe oral mucositis (SOM) , and the incidence of dysgeusia. The main questions it aims to answer are whether lithium-containing mouthwash can effectively prevent and treat radiation-induced oral mucositis and dysgeusia, and whether it will cause adverse events in patients undergoing radiotherapy.

Participants will be instructed to use lithium-containing mouthwash or placebo mouthwash three times daily from the beginning to the end of RT.

Researchers will compare lithium-containing mouthwash group and placebo group to see if lithium-containing mouthwash are beneficial in preventing and treating oral mucositis and dysgeusia in patients undergoing radiotherapy.

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Patients pathologically diagnosed with non-metastatic head and neck malignant tumors; Aged 18-80 years; Eastern Cooperative Oncology Group performance status of ≤2; Planning to receive definitive RT or postoperative adjuvant RT; Normal liver, kidney and bone marrow function; Sign informed consent.

Exclusion Criteria:

Known to be allergic to lithium or other components of mouthwash or severe allergic constitution; Poor oral hygiene and/or severe periodontal diseases; Any previous RT to the head and neck region, Severe kidney disease, severe cardiovascular disease, myasthenia gravis, Parkinson's disease or epilepsy; Recent use or current use of diuretics or other drugs known to interact with lithium; Deemed unsuitable for the study by the investigators (concomitant with any other severe diseases).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.03 mol/L lithium mouthwash; The main ingredients of mouthwash are lithium carbonate and citric acid, transparent colorless liquid. In this group, 10 ml of 0.03 mol/L lithium mouthwash is used to gargle and left in the mouth for 5 min to be spat out from the first day of radiotherapy up to the end of treatment.	Drug: lithium-containing mouthwash; The main ingredients of lithium-containing mouthwash are lithium carbonate and citric acid. A total of 5 concentration gradients of lithium-containing mouthwash are set, including 0.03, 0.06, 0.10, 0.15 and 0.21 mol/L. Mouthwash is used to gargle and left in the mouth for 5 min to be spat out three times a day from the first day of radiotherapy up to the end of treatment.; Drug: lithium-containing mouthwash; Effective lithium salt concentrations screened in the Phase I trial is used as active interventions in this group of interventions. Mouthwash is used to gargle and left in the mouth for 5 min to be spat out three times a day from the first day of radiotherapy up to the end of treatment.
Experimental: 0.06 mol/L lithium mouthwash; The main ingredients of mouthwash are lithium carbonate and citric acid, transparent colorless liquid.. In this group, 10 ml of 0.06 mol/L lithium mouthwash is used to gargle and left in the mouth for 5 min to be spat out from the first day of radiotherapy up to the end of treatment.	Drug: lithium-containing mouthwash; The main ingredients of lithium-containing mouthwash are lithium carbonate and citric acid. A total of 5 concentration gradients of lithium-containing mouthwash are set, including 0.03, 0.06, 0.10, 0.15 and 0.21 mol/L. Mouthwash is used to gargle and left in the mouth for 5 min to be spat out three times a day from the first day of radiotherapy up to the end of treatment.; Drug: lithium-containing mouthwash; Effective lithium salt concentrations screened in the Phase I trial is used as active interventions in this group of interventions. Mouthwash is used to gargle and left in the mouth for 5 min to be spat out three times a day from the first day of radiotherapy up to the end of treatment.
Experimental: 0.10 mol/L lithium mouthwash; The main ingredients of mouthwash are lithium carbonate and citric acid,transparent colorless liquid. In this group, 10 ml of 0.10 mol/L lithium mouthwash is used to gargle and left in the mouth for 5 min to be spat out from the first day of radiotherapy up to the end of treatment.	Drug: lithium-containing mouthwash; The main ingredients of lithium-containing mouthwash are lithium carbonate and citric acid. A total of 5 concentration gradients of lithium-containing mouthwash are set, including 0.03, 0.06, 0.10, 0.15 and 0.21 mol/L. Mouthwash is used to gargle and left in the mouth for 5 min to be spat out three times a day from the first day of radiotherapy up to the end of treatment.; Drug: lithium-containing mouthwash; Effective lithium salt concentrations screened in the Phase I trial is used as active interventions in this group of interventions. Mouthwash is used to gargle and left in the mouth for 5 min to be spat out three times a day from the first day of radiotherapy up to the end of treatment.
Experimental: 0.15 mol/L lithium mouthwash; The main ingredients of mouthwash are lithium carbonate and citric acid, transparent colorless liquid. In this group, 10 ml of 0.15 mol/L lithium mouthwash is used to gargle and left in the mouth for 5 min to be spat out from the first day of radiotherapy up to the end of treatment.	Drug: lithium-containing mouthwash; The main ingredients of lithium-containing mouthwash are lithium carbonate and citric acid. A total of 5 concentration gradients of lithium-containing mouthwash are set, including 0.03, 0.06, 0.10, 0.15 and 0.21 mol/L. Mouthwash is used to gargle and left in the mouth for 5 min to be spat out three times a day from the first day of radiotherapy up to the end of treatment.; Drug: lithium-containing mouthwash; Effective lithium salt concentrations screened in the Phase I trial is used as active interventions in this group of interventions. Mouthwash is used to gargle and left in the mouth for 5 min to be spat out three times a day from the first day of radiotherapy up to the end of treatment.
Active Comparator: Lithium mouthwash; Effective lithium salt concentrations screened in the Phase I trial is used as active interventions in this group of interventions.	Drug: lithium-containing mouthwash; Effective lithium salt concentrations screened in the Phase I trial is used as active interventions in this group of interventions. Mouthwash is used to gargle and left in the mouth for 5 min to be spat out three times a day from the first day of radiotherapy up to the end of treatment.; Drug: lithium-containing mouthwash; The main ingredients of lithium-containing mouthwash are lithium carbonate and citric acid. A total of 5 concentration gradients of lithium-containing mouthwash are set, including 0.03, 0.06, 0.10, 0.15 and 0.30 mol/L. Mouthwash is used to gargle and left in the mouth for 5 min to be spat out three times a day from the first day of radiotherapy up to the end of treatment.
Placebo Comparator: Placebo mouthwash; Placebo Mouthwash is mainly composed of citric acid and sodium hydroxide, transparent colorless liquid.	Drug: Plcacebo mouthwash; Placebo Mouthwash is mainly composed of citric acid and sodium hydroxide, transparent colorless liquid. Mouthwash is used to gargle and left in the mouth for 5 min to be spat out three times a day from the first day of radiotherapy up to the end of treatment.
Experimental: 0.30 mol/L lithium mouthwash; The main ingredients of mouthwash are lithium carbonate and citric acid, transparent colorless liquid. In this group, 10 ml of 0.30 mol/L lithium mouthwash is used to gargle and left in the mouth for 5 min to be spat out from the first day of radiotherapy up to the end of treatment.	Drug: lithium-containing mouthwash; Effective lithium salt concentrations screened in the Phase I trial is used as active interventions in this group of interventions. Mouthwash is used to gargle and left in the mouth for 5 min to be spat out three times a day from the first day of radiotherapy up to the end of treatment.; Drug: lithium-containing mouthwash; The main ingredients of lithium-containing mouthwash are lithium carbonate and citric acid. A total of 5 concentration gradients of lithium-containing mouthwash are set, including 0.03, 0.06, 0.10, 0.15 and 0.30 mol/L. Mouthwash is used to gargle and left in the mouth for 5 min to be spat out three times a day from the first day of radiotherapy up to the end of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of Severe Oral mucositis (WHO grade ≥3)	Oral mucositis is assessed by trained physicians according to World Health Organization (WHO) oral toxicity Scale.	From the start of radiotherapy to 8 weeks after completion of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Common Terminology Criteria for Adverse Events (CTCAE) 5.0 version	From the first day of radiotherapy to the day of the last radiation dose received, usually 6 or 6.5 weeks
Mouth and throat soreness (MTS) scores	Patients report mouth and throat soreness (MTS) scores (Likert scale 1 to 5) via the oral mucositis weekly questionnaire （OMWQ）. Higher score indicates more severe symptoms.	The time period is the period from the start of radiotherapy to the completion of radiotherapy.The evaluation period is approximately 6 weeks and 6 1/2 weeks
Xerostomia	Patients self-rated xerostomia according to summated xerostomia inventory (SXI), and researchers measured saliva flow rates.	1 week before radiotherapy ; at the middle of radiotherapy (3 weeks after the start of radiotherapy) ; at the end of radiotherapy (the last radiation dose received, usually 6 or 6.5 weeks); and 1, 3, 6, 9 and 12 months after the end of radiotherapy
The duration of Severe Oral mucositis (WHO grade ≥3)	The first determination of SOM to the first instance of non-severe OM (WHO grade <3), without a subsequent instance of SOM. Patients without observed SOM were assigned a duration of 0 days.	From the start of radiotherapy to 8 weeks after completion of radiotherapy
The time to onset of Severe Oral mucositis (WHO grade ≥3)	Time from the first day of radiotherapy to the first determination of SOM. Patients without observed SOM were assigned onset days of 6 or 6.5 weeks.	From the start of radiotherapy to 8 weeks after completion of radiotherapy
Taste function	Patients self-rated dysgeusia, Electrogustometer test and taste strips test.	1 week before radiotherapy ; at the middle of radiotherapy (3 weeks after the start of radiotherapy) ; at the end of radiotherapy (the last radiation dose received, usually 6 or 6.5 weeks); and 1, 3, 6, 9 and 12 months after the end of radiotherapy
Patients' quality of life assessment of EORTC QLQ-C30 and H&N35 questionnaires.	EORTC QLQ-C30 and H&N35 questionnaires	1 week before radiotherapy; at the end of radiotherapy(the last radiation dose received, usually 6 or 6.5 weeks); ; and 1, 3, 6, 9 and 12 months after the end of radiotherapy

Collaborators and Investigators

• Sponsor: West China Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Actual): March 1, 2025
• Study Completion (Actual): May 1, 2025

Study Registration Dates

• First Submitted: February 1, 2024
• First Submitted That Met QC Criteria: February 1, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 29, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: head and neck squamous cell carcinoma; nasopharyngeal carcinoma; oral mucositis; Malignant Head and Neck tumors; lithium-containing mouthwash
• Additional Relevant MeSH Terms: Neurologic Manifestations; Mouth Diseases; Stomatognathic Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Glandular and Epithelial; Gastroenteritis; Neoplasms, Squamous Cell; Sensation Disorders; Taste Disorders; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Mucositis; Stomatitis; Dysgeusia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antimanic Agents; Lithium Carbonate
• Other Study ID Numbers: 2023-863

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No