Blinded Dry Mouth Spray Crossover Study

Evaluation of Two Mouth Sprays for Post-irradiation Xerostomia in Head and Neck Cancer Survivors: a Randomized, Double-blind Clinical Trial

To identify the effectiveness of two mouth sprays at relieving symptoms of xerostomia in patients who have received radiation for carcinoma of the head and neck.

To assess patient quality of life and mouth acidity following use of two mouth sprays meant to relieve symptoms of xerostomia in patients who have received radiation for carcinoma of the head and neck.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer; Xerostomia; Xerostomia Following Radiotherapy
• Intervention / Treatment: Other: Remineralizing Extreme Dry Mouth Spray with Xylitol; Device: Alcohol-Free Moisturizing Dry Mouth Spray

Detailed Description

Investigators have observed that patients at the University of Pittsburgh Medical Center Head and Neck Survivorship clinic with symptoms of radiation-induced xerostomia expressed verbal preference for Biotene and Refresh mouth sprays (spray form of mouthwash) compared to other oral products such as gel, toothpaste, and chewing gum. Investigators have designed this study to specifically assess the effectiveness of mouth sprays on xerostomia in patients who have completed radiation for head and neck carcinoma. While there have been clinical trials to evaluate the effectiveness of Biotene oral products for xerostomia, Refresh mouthwash/mouth spray is a newer oral rinse formula that has not undergone any randomized controlled trials to evaluate its efficacy compared to other agents of its kind. The investigators have put forward this randomized controlled trial to compare the efficacy of both sprays to each other and to water. Biotene spray is cleared by the FDA as a medical device product. Currently, Refresh mouth spray falls under the FD&C Act.

There is preliminary data on the effectiveness of Biotene mouthwash for xerostomia in patients who have had radiation of the head and neck. A phase II study of Biotene products (mouthwash, chewing gum, and toothpaste) were effective at improving many symptoms of post-irradiation xerostomia. Numerous other studies have shown that mouthwash and topical dry mouth products improve xerostomia symptoms.

Xerostomia, or mouth dryness, is a frequent side effect of head and neck cancer radiation therapy, as the salivary glands are often damaged during therapy. Radiation therapy can be successful in treating cancer, but post-irradiation xerostomia can cause oral discomfort as well as issues with eating, speech, and oral hygiene, leading to significantly decreased quality of life. While treatment of xerostomia has limited benefit, various mouthwashes have led to major symptomatic improvement in some patients. This study will add to existing literature by commenting on efficacy of a popular and established mouth spray used for xerostomia as well as a new mouth spray that has not been compared to existing formulas. A double-blinded randomized controlled trial evaluating these mouth sprays will add information about value of both formulas for head and neck carcinoma survivors with radiation-induced xerostomia.

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tina Harrison, BS; Phone Number: 412-953-4850; Email: harrisonta@upmc.edu
• Study Contact Backup: Name: Jonas T Johnson, MD; Phone Number: (412) 647-2130; Email: johnsonjt@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC
    • Pittsburgh, Pennsylvania, United States, 15219
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• biopsy-proven oral cavity, oropharynx, larynx, and hypopharynx carcinoma
• who received primary radiation with curative intent (>50 Gray in 20 fractions)
• radiation treatment completed greater than 6 months ago
• who endorse xerostomia

Exclusion Criteria:

• evidence of metastasis or recurrent disease
• Current use of pilocarpine, antidepressants, anticholinergic drugs, or any other medication that has an effect on salivation
• those who have documented medical conditions associated with xerostomia such as Sjogren's Syndrome
• those who use oral inhalants for the treatment of respiratory disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Biotene Spray, followed by Refresh Spray; The Biotene Spray followed by Refresh Spray Arm will be asked to complete a 2 week trial using Biotene Spray first, then will be asked to complete a 2 week trial using Refresh Spray second. (after the appropriate 1 week washout periods have been completed)	Other: Remineralizing Extreme Dry Mouth Spray with Xylitol; oral hydrating spray; Other Names: Refresh Oral Hydrating Spray; Device: Alcohol-Free Moisturizing Dry Mouth Spray; oral hydrating spray; Other Names: Biotene
Other: Refresh Spray, followed by Biotene Spray; The Refresh Spray, followed by Biotene Spray Arm will be asked to complete a 2 week trial using Refresh Spray first, then will be asked to complete a 2 week trial using Biotene Spray second. (after the appropriate 1 week washout periods have been completed)	Other: Remineralizing Extreme Dry Mouth Spray with Xylitol; oral hydrating spray; Other Names: Refresh Oral Hydrating Spray; Device: Alcohol-Free Moisturizing Dry Mouth Spray; oral hydrating spray; Other Names: Biotene

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral Dryness	at the end of each study period an online questionnaire was administered. The questionnaire included continuous variables derived from the 100mm visual analog scale (VAS); documented via questionnaire completion by participants administered via Qualtrics. Dryness was measured on a 0-100 point scale "During the last three days, overall, your mouth or tongue was: 'Very Dry' = 0 10 20 30 40 50 60 70 80 90 100 = 'Not at All Dry"	2 week trial period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleeping Difficulty Due to Oral Dryness	sleeping difficulty due to oral dryness was documented via questionnaire completion by participants administered via Qualtrics. Sleeping difficulty will be measured on a 0-100 point scale "During the last three days, due to the dryness of your mouth and tongue, how difficult was it to sleep? Consider such factors as how difficult it was for you to go to sleep, the duration and quality of your sleep, and how often you woke up to drink or urinate. Very Difficult 0 10 20 30 40 50 60 70 80 90 100 Easy" (Higher score means better outcome)	2 week trial
Speaking Difficulty Due to Oral Dryness	Speaking difficulty due to oral dryness was documented via questionnaire completion by participants administered via Qualtrics. Speaking difficulty will be measured on a 0-100 point scale "During the last three days, due to the dryness of your mouth and tongue, how difficult was it to speak without drinking liquids? Very Difficult 0 10 20 30 40 50 60 70 80 90 100 Easy"	2 week trial
Taste Alteration/Impairment Due to Oral Dryness	Alteration/impairment in sense of taste will be documented via questionnaire completion by participants administered via Qualtrics. Taste alteration/impairment will be measured on a 0-100 point scale "During the last three days, has your sense of taste been impaired or affected? Greatly Impaired/Affected 0 10 20 30 40 50 60 70 80 90 100 Not Impaired/Affected"	2 week trial
Swallowing and Chewing Difficulty Due to Oral Dryness	Swallowing and chewing difficulty due to oral dryness will be documented via questionnaire completion by participants administered via Qualtrics. Swallowing and chewing difficulty will be measured on a 0-100 point scale "During the last three days, overall, due to the dryness of your mouth and tongue, how difficult was it to chew and swallow food? Very Difficult 0 10 20 30 40 50 60 70 80 90 100 Easy"	2 week trial
Saliva PH	PH Is a measure of acidity on a logarithmic scale range 0 (most acidic) to 14 (most basic) with a neutral PH of 7 as the desired outcome.	2 week trial
Difficulty Wearing Dental Prostheses (if Applicable)	Difficulty wearing dental prostheses (if applicable) will be documented via questionnaire completion by participants administered via Qualtrics. Dental prostheses wearing difficulty will be measured on a 0-100 point scale "If you normally wear dentures, due to the dryness of your mouth and tongue, how difficult was it to wear dentures during the last three days? (If you do not normally wear dentures or could not wear dentures for other reasons not associated with dry mouth, please check the box marked "Not applicable") Very Difficult 0 10 20 30 40 50 60 70 80 90 100 Easy Not Applicable	6 weeks

Collaborators and Investigators

• Sponsor: Jonas Johnson
• Collaborators: TJA Health, LLC
• Investigators: Principal Investigator: Jonas T Johnson, MD, University of Pittsburgh

Publications and helpful links

General Publications

• Epstein JB, Emerton S, Le ND, Stevenson-Moore P. A double-blind crossover trial of Oral Balance gel and Biotene toothpaste versus placebo in patients with xerostomia following radiation therapy. Oral Oncol. 1999 Mar;35(2):132-7. doi: 10.1016/s1368-8375(98)00109-2.
• Warde P, Kroll B, O'Sullivan B, Aslanidis J, Tew-George E, Waldron J, Maxymiw W, Liu FF, Payne D, Cummings B. A phase II study of Biotene in the treatment of postradiation xerostomia in patients with head and neck cancer. Support Care Cancer. 2000 May;8(3):203-8. doi: 10.1007/s005200050286.
• Eisbruch A, Rhodus N, Rosenthal D, Murphy B, Rasch C, Sonis S, Scarantino C, Brizel D. How should we measure and report radiotherapy-induced xerostomia? Semin Radiat Oncol. 2003 Jul;13(3):226-34. doi: 10.1016/S1053-4296(03)00033-X.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2021
• Primary Completion (Actual): November 15, 2022
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: October 18, 2020
• First Submitted That Met QC Criteria: October 28, 2020
• First Posted (Actual): October 29, 2020

Study Record Updates

• Last Update Posted (Actual): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Mouth Spray
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Head and Neck Neoplasms; Xerostomia
• Other Study ID Numbers: STUDY20090008

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: Yes
• product manufactured in and exported from the U.S.: Yes