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

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.

Study Overview

• Status: Completed
• Conditions: Xerostomia, Hyposalivation, Saliva Substitute, Radiation-induced Toxicity, Nasopharyngeal Cancer
• Intervention / Treatment: Diagnostic test: Summated Xerostomia Inventory; Diagnostic test: Sialometry

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Malaysia
  • Kuala Lumpur
    • Cheras, Kuala Lumpur, Malaysia, 56000
      • Universiti Kebangsaan Malaysia Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universiti Kebangsaan Malaysia Medical Centre
• Investigators: Principal Investigator: Mawaddah Azman, MS, National University of Malaysia

Publications and helpful links

General Publications

• Gravenmade EJ, Vissink A. Mucin-containing lozenges in the treatment of intraoral problems associated with Sjogren's syndrome. A double-blind crossover study in 42 patients. Oral Surg Oral Med Oral Pathol. 1993 Apr;75(4):466-71. doi: 10.1016/0030-4220(93)90172-z.
• Marimuthu D, Han KM, Mohamad MSF, Azman M. Saliva substitute mouthwash in nasopharyngeal cancer survivors with xerostomia: a randomized controlled trial. Clin Oral Investig. 2021 May;25(5):3105-3115. doi: 10.1007/s00784-020-03634-5. Epub 2020 Nov 11.

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2018
• Primary Completion (Actual): January 5, 2020
• Study Completion (Actual): March 5, 2020

Study Registration Dates

• First Submitted: July 24, 2020
• First Submitted That Met QC Criteria: July 24, 2020
• First Posted (Actual): July 29, 2020

Study Record Updates

• Last Update Posted (Actual): July 29, 2020
• Last Update Submitted That Met QC Criteria: July 24, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Mouth Diseases; Salivary Gland Diseases; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Xerostomia
• Other Study ID Numbers: FF2018-133

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: IPD will be shared upon publication of the research

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