Study on the Effects of a Toothpaste in the Microbiome and Clinical Parameters in Patients With Oral Dysbiosis

Study Overview
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Brief Summary
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Dysbiosis is a situation in which the normal function of an ecological net is altered. In health there is a cross talk between the host and the microbiota in order to maintain and promote a state of eubiosis. In dysbiosis a state of inflammation, a loss of hydration, a change in pH, a loss of the barrier function are all allies of key pathogens that work against the host. Stop dysbiosis is a bigger multibranch project focussed on different aspects of clinical dysbiosis including this prospective interventional double blind randomised clinical trial. Stop dysbiosis comprises further clinical studies in several areas such as oral dysbiosis, skin dysbiosis, vaginal dysbiosis and cancer dysbiosis, between others. One of the most common dysbiosis of the mouth is periodontal and mucosa dysbiosis that courses with inflammation of the gingiva (gingivitis). This inflammation induces some enzymes that in a later stage destroy connective tissue. The current study beeing presented now is focussed to research the effect of a composition with Saliactive ® topically delivered to the oral cavity vehiculized in an everyday toothpaste (YOTUEL® microbiome toothpaste) in a group of patients with oral dysbiosis.

Detailed Description
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Oral microbiota is formed by diverse bacteria, archea, protozoos, yeast and funghi. More than 700 species of bacteria have been identified in the mouth. These bacteria live in equilibria in conditions of health. When equilibria is lost, due to changes in microbiota or changes in the ecosystem, dysbiosis appears. Periodontal dysbiosis is the consequence of the accumulation of plaque and the increase of gram negative species capable of releasing virulence factors that maintain inflammation and bleeding that maintain the ecosystem in a disease promoting status. Oral hygiene is a daily personal protocol effective means of delivery different substances to the tissues of the oral cavity. Toothpaste, mouthrinse, topical gels, lozenges and sprays are the most common presentations used in the oral cavity. The standard of care in the oral compound is toothpaste used 2-3 times a day. The toothpaste that is going to be tested in the study does not contain any anymicrobial agent and includes an olive product, betaine and xylitol. Its efficacy will be tested measuring the inflammatory profile that includes plaque index and bleeding index, the microbiota population by genetic sequenciation of the ADNr 16s, the salivary flow, the colour ot teeth and the nitrates/nitrites ratio at baseline, after 2 months and 4 months using the product. Two controls will be also analysed to compare results, one with the same composition but without the 3 ingredients olive product, betaine and xylitol, and one product marketed as a toothpaste for gingivitis with an antibacterial ingredient. Assignation of the 100 subjects will be randomized and the products are blind for the subjects and the researcher.

Official Title
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Stop Oral Dysbiosis. Study on the Effects of a Toothpaste in the Inflammatory Profile, Microbiome and Other Oral Dysbiosis Parameters: A Controlled, Randomized, Double-blind Study. This Study is Part of the Stop Dysbiosis Project

Conditions
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Oral Dysbiosis

Intervention / Treatment
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* Combination Product: Test
* Combination Product: Placebo
* Combination Product: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnose of gingivitis. At least 20 teeth (3rd molars excluded). Must Accept informed consent. Exclusion Criteria: Clinical diagnose of periodontitis. With orthodontics. With removable dentures. With upper incisors restorated. Tumours in soft or hard tissues of the mouth. More than 5 caries lesions with immediate restorative need Antibiotics intake less than one month ago. Pregnant women. Other clinic assay at the moment. Dental prophylaxis less than 2 weeks before starting the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: Three toothpastes will be included in the study; one with the composition including an olive product, betaine and xylitol, one with the same composition but without the olive product, betaine and xylitol, and one of a product marketed for gingivitis with and antimicrobial ingredient. Subjects are randomnly assigned and products will have a white label so that nor subject nor researcher will know the composition to be tested.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test product<br>Toothpaste including an olive product, betaine and xylitol. | Combination Product: Test<br>* Toothpaste including a Saliactive® that is the combination of an olive product, betaine and xylitol.<br>|
| Placebo Comparator: Placebo product<br>Toothpaste with the same composition as the test product but without olive product, betaine and xylitol. | Combination Product: Placebo<br>* Toothpaste with the same composition as the test product but without Saliactive®.<br>|
| Active Comparator: Control product<br>Toothpaste marketed for gingivitis with zinc mineral with antimicrobial activity. | Combination Product: Control<br>* Toothpaste marketed for gingivitis with zinc citrate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline Microbiota at 4 months | ADNr 16s genetic sequencing | 4 months | 
| Change from Baseline Salivary flow rate at 2 months and at 4 months | Unstimulated salivary flow rate recovery as per Navazesh | 4 months | 
| Change from Baseline Saliva pH at 2 months and at 4 months | pH meter | 4 months | 
| Change from Baseline Bleeding index at 2 months and at 4 months | Ainamo and Bay bleeding index indicating the percentage of bleeding from 0 (no bleeding) to 100 (maximum bleeding) | 4 months | 
| Change in Baseline Plaque index at 2 months and at 4 months | Tonetti plaque index | 4 months | 
| Change in Baseline Elastase at 2 months and at 4 months | ELISA | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Baseline nitrate and nitrite in saliva at 4 months | Ionic chromatography | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gum inflammation, Periodontal Dysbiosis, Oral Dysbiosis