Saliva Substitute Mouthwash in NPC Survivors With Xerostomia: A Randomized Controlled Trial

Study Overview
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Brief Summary
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Nasopharyngeal carcinoma (NPC) is the highest reported otorhinolaryngological malignancy reported in Malaysia affecting predominantly male adults between 40-60 years old [1, 2]. Radiation therapy (RT) has been coined as the mainstay treatment owing to its' radiosensitive properties [1, 3]. Radiation-induced DNA damage impairs proper cell division, resulting in cell death or senescence of cells that attempt to divide, particularly useful in killing malignant cells. However, radiation doses to the salivary glands cause loss of saliva producing acinar cells which ultimately hampers production of saliva in NPC patients post radiation [4]. This leads to progressive loss of salivary gland function causing xerostomia symptoms [5]. This study aims to compare the effects of two mouthwashes in the treatment of xerostomia.

Detailed Description
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Xerostomia, or dry mouth caused by reduced or absent saliva flow, is a subjective symptom that can lead to impaired chewing, swallowing, altered sense of taste and speech. This eventually affects their nutritional status and quality of life. The reported prevalence of xerostomia in NPC survivors ranged from 80% -100% [6-9]. This high prevalence has stemmed a lot of interest in prevention and treatment of this important sequelae. Saliva substitute in the forms of gels, toothpaste, sprays or mouthwash has been used for treatment of xerostomia [10]. Oral7® mouthwash (Oral7 International, United Kingdom) is a mucin-based saliva substitute formulated with natural enzymes such as lactoperoxidase, lysozyme, glucose oxidase and lactoferrin, similar to naturally occuring saliva. The biophysical properties of the mouthwash can potentially provide relief to xerostomia symptoms in patients post radiotherapy translating to a better quality of life. Hence, the purpose of the present study is to evaluate the effects of saliva substitute in treating xerostomia among NPC patients post radiotherapy. The primary end-point of the study was to compare the subjective xerostomia symptoms, measured using a validated inventory taken 4 weeks following intervention and at baseline between patients who did not receive and patients who received Oral7® mouthwash. The secondary end-point was to demonstrate similar changes in objective measurements using sialometry techniques.

Official Title
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Saliva Substitute Mouthwash in NPC Survivors With Xerostomia: A Randomized Controlled Trial

Conditions
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Xerostomia, Hyposalivation, Saliva Substitute, Radiation-induced Toxicity, Nasopharyngeal Cancer

Intervention / Treatment
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* Diagnostic Test: Summated Xerostomia Inventory
* Diagnostic Test: Sialometry


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have completed radiation therapy or concurrent chemotherapy and radiation therapy for nasopharyngeal carcinoma (clinical staging of tumour based on AJCC staging (8th edition) T1-4, N0-3, M0). Patients age 20 years old to 85 years old. Two months has elapsed since last dose of chemotherapy or radiotherapy Karnofsky performance score more than 70%. Patients complaining of xerostomia. Exclusion Criteria: Those contraindicated to using mouthwash (established allergy to lactoperoxidase, lysozyme, glucose oxidase lactoferrin, cetylpyridinium chloride and xylitol) Patients with residual or recurrent disease. Patients who received intensity modulated radiation therapy. Patients with ongoing oral mucositis (WHO Oral Mucositis grading I to IV) Patients with facial, glossopharyngeal. vagus and hypoglossal nerve palsy/ paresis. Patients who had any form of concurrent treatment protocols (hormonal, alternative, antiviral, sialogogues or photodynamic therapy) during the study duration. Patients with autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and Sjớgren syndrome.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional<br>4 weeks use of mucin-based saliva substitute | Diagnostic Test: Summated Xerostomia Inventory<br>* structured interview by a dedicated researcher to obtain a score of the summated xerostomia inventory (SXI)<br>Diagnostic Test: Sialometry<br>* unstimulated whole saliva (UWS) flow measurement<br>|
| Placebo Comparator: Control<br>4 weeks use of xylitol-based mouthwash | Diagnostic Test: Summated Xerostomia Inventory<br>* structured interview by a dedicated researcher to obtain a score of the summated xerostomia inventory (SXI)<br>Diagnostic Test: Sialometry<br>* unstimulated whole saliva (UWS) flow measurement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| summated xerostomia inventory (SXI) score | summated xerostomia inventory (SXI) score at baseline-summated xerostomia inventory (SXI) score at 4 weeks post intervention | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| unstimulated whole saliva (UWS) flow | unstimulated whole saliva (UWS) flow at 4 weeks post intervention -unstimulated whole saliva (UWS) flow at baseline | 4 weeks |