Head and Neck Cancer, Xerostomia, Xerostomia Following Radiotherapy
Conditions
Keywords
Mouth Spray
Brief summary
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.
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.
Interventions
OTHERRemineralizing Extreme Dry Mouth Spray with Xylitol
oral hydrating spray
DEVICEAlcohol-Free Moisturizing Dry Mouth Spray
oral hydrating spray
Sponsors
TJA Health, LLC
Jonas Johnson
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Both subjects and clinicians will be blinded to Mouth Spray A and Mouth Spray B.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oral Dryness | 2 week trial period | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Speaking Difficulty Due to Oral Dryness | 2 week trial | 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 |
| Taste Alteration/Impairment Due to Oral Dryness | 2 week trial | 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 |
| Sleeping Difficulty Due to Oral Dryness | 2 week trial | 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) |
| Saliva PH | 2 week trial | 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. |
| Difficulty Wearing Dental Prostheses (if Applicable) | 6 weeks | 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 |
| Swallowing and Chewing Difficulty Due to Oral Dryness | 2 week trial | 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 |
Countries
United States
Participant flow
Recruitment details
1824 patients were screened for eligibility at UPMC's Head and Neck Cancer Survivorship Clinic between January 2021 and September 2022.
Pre-assignment details
468 patients were found eligible, 339 declined to participate and 129 were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| 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)
Remineralizing Extreme Dry Mouth Spray with Xylitol: oral hydrating spray
Alcohol-Free Moisturizing Dry Mouth Spray: oral hydrating spray | 69 |
| 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)
Remineralizing Extreme Dry Mouth Spray with Xylitol: oral hydrating spray
Alcohol-Free Moisturizing Dry Mouth Spray: oral hydrating spray | 60 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (2 Weeks) | Lost to Follow-up | 3 | 1 |
| First Intervention (2 Weeks) | mild adverse effects | 1 | 3 |
| First Wash Out (1 Week) | Withdrawal by Subject | 12 | 6 |
| Second Intervention (2 Week) | Lost to Follow-up | 2 | 4 |
| Second Intervention (2 Week) | mild adverse effect | 0 | 1 |
Baseline characteristics
| Characteristic | Biotene Spray, Followed by Refresh Spray | Refresh Spray, Followed by Biotene Spray | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 34 Participants | 29 Participants | 63 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 31 Participants | 66 Participants |
| Drymouth baseline | 44.0 units on a scale STANDARD_DEVIATION 20.6 | 39.2 units on a scale STANDARD_DEVIATION 21.8 | 42.4 units on a scale STANDARD_DEVIATION 21 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 68 Participants | 56 Participants | 124 Participants |
| Region of Enrollment United States | 69 Participants | 60 Participants | 129 Participants |
| Sex: Female, Male Female | 14 Participants | 12 Participants | 26 Participants |
| Sex: Female, Male Male | 55 Participants | 48 Participants | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 129 | 0 / 129 |
| other Total, other adverse events | 0 / 129 | 5 / 129 |
| serious Total, serious adverse events | 0 / 129 | 0 / 129 |
Outcome results
Primary
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
Time frame: 2 week trial period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biotene Spray | Oral Dryness | Oral dryness Dryness baseline | 45.5 units on a scale | Standard Deviation 20.3 |
| Biotene Spray | Oral Dryness | Dryness 2 weeks | 52.76 units on a scale | Standard Deviation 19.25 |
| Refresh Spray | Oral Dryness | Oral dryness Dryness baseline | 46.6 units on a scale | Standard Deviation 22.7 |
| Refresh Spray | Oral Dryness | Dryness 2 weeks | 54.1 units on a scale | Standard Deviation 21.6 |
Comparison: Null hypothesis is that there was no difference in change of Dry mouth score between Refresh and Biotene. ANCOVA model was performed by regressing the difference in after-treatment measurement between Refresh and Biotene over the difference of baseline between Refresh and Biotene. The test was performed with a significance level of 0.05 (two- sided)p-value: <0.501ANCOVA
Secondary
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
Time frame: 6 weeks
Population: No participants in study with dental prosthesis, therefore data was not collected.
Secondary
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.
Time frame: 2 week trial
Population: The number of participants in this analysis are lower than the overall population due to missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biotene Spray | Saliva PH | PH baseline | 5.3 units on a scale | Standard Deviation 1 |
| Biotene Spray | Saliva PH | PH 2 weeks | 5.4 units on a scale | Standard Deviation 1 |
| Refresh Spray | Saliva PH | PH baseline | 5.5 units on a scale | Standard Deviation 1.1 |
| Refresh Spray | Saliva PH | PH 2 weeks | 5.5 units on a scale | Standard Deviation 1.1 |
p-value: 0.486ANCOVA
Secondary
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)
Time frame: 2 week trial
Population: Number of participants in analysis is less than overall number of participants due to missing responses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biotene Spray | Sleeping Difficulty Due to Oral Dryness | Sleep Baseline | 56.3 units on a scale | Standard Deviation 27 |
| Biotene Spray | Sleeping Difficulty Due to Oral Dryness | Sleep 2 weeks | 66.8 units on a scale | Standard Deviation 23 |
| Refresh Spray | Sleeping Difficulty Due to Oral Dryness | Sleep Baseline | 61.9 units on a scale | Standard Deviation 26.3 |
| Refresh Spray | Sleeping Difficulty Due to Oral Dryness | Sleep 2 weeks | 64.8 units on a scale | Standard Deviation 24.9 |
p-value: 0.109ANCOVA
Secondary
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
Time frame: 2 week trial
Population: The number of participants in analysis are lower in this specific analysis due to missing data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biotene Spray | Speaking Difficulty Due to Oral Dryness | speaking baseline | 60.8 units on a scale | Standard Deviation 27.6 |
| Biotene Spray | Speaking Difficulty Due to Oral Dryness | speaking 2 weeks | 69.9 units on a scale | Standard Deviation 22.2 |
| Refresh Spray | Speaking Difficulty Due to Oral Dryness | speaking baseline | 63.0 units on a scale | Standard Deviation 26.6 |
| Refresh Spray | Speaking Difficulty Due to Oral Dryness | speaking 2 weeks | 66.8 units on a scale | Standard Deviation 24.1 |
p-value: 0.107ANCOVA
Secondary
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
Time frame: 2 week trial
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biotene Spray | Swallowing and Chewing Difficulty Due to Oral Dryness | swallowing baseline | 53.7 units on a scale | Standard Deviation 25.6 |
| Biotene Spray | Swallowing and Chewing Difficulty Due to Oral Dryness | swallowing 2 weeks | 62.7 units on a scale | Standard Deviation 24.1 |
| Refresh Spray | Swallowing and Chewing Difficulty Due to Oral Dryness | swallowing baseline | 54.6 units on a scale | Standard Deviation 24.4 |
| Refresh Spray | Swallowing and Chewing Difficulty Due to Oral Dryness | swallowing 2 weeks | 60.4 units on a scale | Standard Deviation 23.4 |
p-value: 0.213ANCOVA
Secondary
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
Time frame: 2 week trial
Population: The number of participants in this analysis are lower than the overall population due to missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biotene Spray | Taste Alteration/Impairment Due to Oral Dryness | Taste baseline | 73.2 units on a scale | Standard Deviation 29 |
| Biotene Spray | Taste Alteration/Impairment Due to Oral Dryness | Taste 2 weeks | 78.1 units on a scale | Standard Deviation 22.8 |
| Refresh Spray | Taste Alteration/Impairment Due to Oral Dryness | Taste baseline | 71.5 units on a scale | Standard Deviation 29.3 |
| Refresh Spray | Taste Alteration/Impairment Due to Oral Dryness | Taste 2 weeks | 75.4 units on a scale | Standard Deviation 27 |
p-value: 0.489ANCOVA