Oral Care Protocol for the Management of Chemotherapy and Radiation Therapy-Induced Oral Mucositis

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of a novel oral care protocol on the severity and pain of oral mucositis in patients receiving radiation and/or chemotherapy for head and neck cancers. The secondary objectives are to characterize the microbiome associated with oral mucositis, measure salivary proinflammatory cytokines, and evaluate other clinical indicators of the intervention. Participants will be enrolled prior to beginning radiation and/or chemotherapy, and will be randomized to receive either the oral health protocol or standard of care oral hygiene.

Detailed Description
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Oral mucositis (OM) is one of the most debilitating adverse effects in cancer patients treated with chemotherapy or radiation (RT). Currently, there are no effective therapies or prevention for mucositis, while several clinical studies have suggested that professional oral care could effectively reduce the severity of Radiation Therapy or chemotherapy-induced oral mucositis. Palliative treatment, rather than preventive or curative measures, remains the standard of care. Evidence-based guidelines do not provide consistent recommendations for the prevention, treatment and management of oral mucositis. The investigators hypothesize that a monitored regimen of professional oral hygiene prevents harmful ecological shifts in the oral cavity, improve oral health and reduce the duration and severity of Oral Mucositis in cancer patients, consequently improving their overall quality of life during treatment. Moreover, the investigators hypothesize that the weekly oral hygiene regimen performed by an oral health professional is more effective in treating and preventing mucositis than current standard-of-care treatments. The principal investigator of this project has developed a novel oral care regimen protocol for the treatment of oral mucositis. The Oral Mucosa Deterging and Periodontal Debridement (OMDP) protocol consists of a regimen of frequent professional oral prophylaxis including tooth cleaning, tooth polishing and flossing, and the debridement of the periodontium and deterging of the oral mucosa. This is an intervention that is implemented prior to and maintained throughout the entire cycle of the radiation or chemoradiation. Co-adjuvant treatments such as intense fluoride treatments, oral hygiene instructions and palliative mouth-rinses are also part of the protocol. The hypothesis is that repeated professional prophylaxis of the oral cavity would protect the healthy oral tissue against infection and inflammation often associated with severe cases of mucositis, and consequently reduces mucositis incidence and duration. Participants in this study would attend approximately 9 study visits over the course of 16-18 weeks, depending on their specific cancer treatment plan. Study participants will be randomized to receive either the oral health protocol, which they will receive on a weekly basis, or standard of care oral hygiene instructions and tooth brushing, preformed on a bi-weekly basis.

Official Title
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Oral Care Protocol for the Management of Chemotherapy and Radiation Therapy-Induced Oral Mucositis

Conditions
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Oral Mucositis, Oral Cancer

Intervention / Treatment
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* Procedure: Oral Mucosa Deterging and Periodontal Debridement (OMDP)
* Procedure: Standard of Care Oral Hygiene Instructions
* Procedure: Dental scaling, ultrasonic
* Other: Chlorhexidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patient aged 18 years or older; Patients must sign an informed consent before data collection, screening, or initiation of study procedures; Patients who are scheduled to undergo radiation or chemoradiation treatment for head/neck cancer; Patients who have a minimum of 6 natural teeth at the time of enrollment. Exclusion Criteria: Female patients who are pregnant or lactating at the baseline/screening visit; Patient participating in another biomedical/oral health research study that would interfere with participating in this study; Patient deprived of freedom, under supervision or guardianship; Patient unable to attend to scheduled medical monitoring due to geographical, social or mental reasons; Immune compromised or other serious medical conditions, regardless of whether the condition is controlled or not; Patient who requires pre-medication prior to dental treatment; Any patient, in the opinion of the Investigator, who is unable or unlikely to comply fully with the study requirements or procedures for any reason (e.g. major surgical resection of intra-oral structures which would prevent oral care intervention, edentulous, severe periodontal disease, etc).

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OMDP Group<br>Subjects randomized to this group will attend weekly visits and receive a full dental cleaning, as well as have their gums/tongue cleaned by a dental professional. Subjects will also receive standard of care oral hygiene instructions. | Procedure: Oral Mucosa Deterging and Periodontal Debridement (OMDP)<br>* OMDP consists of a regimen of frequent professional oral prophylaxis including tooth cleaning, tooth polishing and flossing, and the cleaning of the periodontum and oral mucosa. This is an intervention that is implemented prior to and maintained throughout the entire cycle of the radiation or chemoradiation.<br>Procedure: Dental scaling, ultrasonic<br>* An ultrasonic dental scaler will be used to clean the teeth<br>Other: Chlorhexidine<br>* Non-alcoholic chlorhexidine will be used as part of the OMDP protocol<br>|
| Other: Control Group<br>Subjects assigned to the control group will receive standard of care oral health instructions and will come for bi-weekly treatment visits where they will have their teeth cleaned (brushed) by a dental professional. | Procedure: Standard of Care Oral Hygiene Instructions<br>* Subjects assigned to this intervention will receive standard of care oral hygiene instructions, including in-person instruction and materials to reference at home. Subjects will also have their teeth brushed and flossed bi-weekly by a dental professional.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oral Mucositis Severity - WHO Scale | OM severity will be assessed by the WHO Oral Mucositis Scale at each follow-up visit. The WHO Oral Mucositis Scale is a 5 point scale (0 to 4) with the following scoring system: 0=None Soreness with erythema Erythema, ulcers, can eat solids Ulcers, liquid diet only Alimentation not possible | End of Radiation Treatment (approximately week 7) | 
| Oral Mucositis Severity - NCI Scale | OM severity will be assessed by the NCI-CTCAE Scale (National Cancer Institute - Common Toxicity Criteria and Grading of Adverse Events) at each follow-up visit. The NCI-CTCAE is a 5 point scale (1-5) with the following grading system: Erythema of the mucosa Patchy ulcerations or pseudomembranes Confluent ulcerations or pseudomembranes; bleeding with minor trauma Tissue necrosis; significant spontaneous bleeding; life-threatening consequences Death | End of Radiation Treatment (approximately week 7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of Oral Pain (FACES Scale) | The FACES Scale is a 6 point scale which ranges from 0-10 (and includes even numbers only). The scale is accompanied by illustrations of faces which represent each score. The subjects is shown the scale and asked to choose the face that best depicts the pain they are experiencing. 0=No hurt 2=Hurts a little bit 4=Hurts a little more 6=Hurts even more 8=Hurts a whole lot 10-Hurts the worst you could imagine | End of Radiation Treatment (approximately week 7) | 
| Mean Difference in the Relative Abundance of Oral Microbial Species of the Cheek (Right Side) From Baseline to Onset of Oral Mucositis | The number of each type of microbial species will be quantified and compared at each follow-up visit. Relative abundance for each species will be measured and reported. Relative abundance is a measure of the proportion of an organism of a particular kind (in this case, each microbial species) relative to the total number of organisms (the other microbial species) in the area. A positive mean value indicates that the species was present in greater quantities at baseline. A negative mean value indicates that the species was present in greater quantities at onset of oral mucositis. For this data, the top five most abundant microbial species are presented. | Baseline to Onset of Oral Mucositis | 
| Mean Difference in the Relative Abundance of Oral Microbial Species of the Cheek (Left Side) From Baseline to Onset of Oral Mucositis | The number of each type of microbial species will be quantified and compared at each follow-up visit. Relative abundance for each species will be measured and reported. Relative abundance is a measure of the proportion of an organism of a particular kind (in this case, each microbial species) relative to the total number of organisms (the other microbial species) in the area. A positive mean value indicates that the species was present in greater quantities at baseline. A negative mean value indicates that the species was present in greater quantities at onset of oral mucositis. For this data, the top five most abundant microbial species are presented. | Baseline to Onset of Oral Mucositis | 
| Mean Difference in the Relative Abundance of Oral Microbial Species of the Tongue (Right Side) From Baseline to Onset of Oral Mucositis | The number of each type of microbial species will be quantified and compared at each follow-up visit. Relative abundance for each species will be measured and reported. Relative abundance is a measure of the proportion of an organism of a particular kind (in this case, each microbial species) relative to the total number of organisms (the other microbial species) in the area. A positive mean value indicates that the species was present in greater quantities at baseline. A negative mean value indicates that the species was present in greater quantities at onset of oral mucositis. For this data, the top five most abundant microbial species are presented. | Baseline to Onset of Oral Mucositis | 
| Mean Difference in the Relative Abundance of Oral Microbial Species of the Tongue (Left Side) From Baseline to Onset of Oral Mucositis | The number of each type of microbial species will be quantified and compared at each follow-up visit. Relative abundance for each species will be measured and reported. Relative abundance is a measure of the proportion of an organism of a particular kind (in this case, each microbial species) relative to the total number of organisms (the other microbial species) in the area. A positive mean value indicates that the species was present in greater quantities at baseline. A negative mean value indicates that the species was present in greater quantities at onset of oral mucositis. For this data, the top five most abundant microbial species are presented. | Baseline to Onset of Oral Mucositis | 
| Change in the Level of Salivary Proinflammatory Cytokines From Baseline to 16 Weeks | The level of salivary proinflammatory cytokines will be compared between the two groups at each follow-up visit. | Baseline and 16 weeks (final study visit) | 
| Change in Quality of Life as Measured by the Composite Score of the EORTC | Quality of life will be measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) and Head & Neck module (EORTC-H&N) and compared between the two groups at each follow-up visit. There is not a single composite score for the entire questionnaire, but rather composite scores for each type of assessment (e.g. physical functioning, global health, swallowing, etc.). Possible scores range from 0-100. A lower score indicates low levels of that trait, which a higher score indicates high levels of that trait (e.g. a 100 for physical functioning indicates a high level of physical function). | Baseline to the peak of mucositis (approximately week 4) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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proinflammatory cytokines, microbiome, radiation therapy