Effects of a Composition on the Oral Microbiome, pH, Nitrite/Nitrate Ratio, Elastases and Inflammation in Oral Dysbiosis

Phase 2

Completed

• Conditions: Oral Dysbiosis
• Interventions: Drug: Test composition Saliactive® (olive product, betaine and xylitol); Drug: Placebo; Drug: Control

• Registration Number: NCT05463484
• Lead Sponsor: Mucosa Innovations, S.L.

Brief Summary

Dysbiosis is a condition in which the normal function of an ecological net is altered. 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 initiate invasion and cytokine and pro-inflammatory mediators release that target other tissues and organs resulting in chronic inflammatory conditions.

In health there is a cross-talk between the host and the microbiota in order to maintain and promote a state of eubiosis with a local and general health gain. Dysbiosis reversion has not been solved with the use of antibacterials, antiseptics nor antibiotics.

Stop dysbiosis project is focussed on different aspects of human dysbiosis such as oral dysbiosis, skin dysbiosis, vaginal dysbiosis and cancer dysbiosis, between others including the current prospective interventional double-blind randomised clinical trial.

One of the most common oral dysbiosis is periodontal and mucosa dysbiosis that courses with inflammation of the gingiva (gingivitis). This inflammation induces specific enzymes that in a later stage destroy connective tissue. The current clinical trial analyzes the effect of a composition (Saliactive ®) delivered to the oral cavity via a daily use toothpaste (YOTUEL® microbiome toothpaste) in a group of patients with oral dysbiosis.

Detailed Description

Oral microbiota is the most diverse of the human body. It consists of mainly commensal bacteria, archea, protozoos, yeast and funghi. More than 700 species of bacteria have been identified in the mouth. In conditions of health these bacteria live in equilibrium. In inflammatory conditions, balance is lost, due to changes in microbiota or in the ecosystem with lost of the mucosa barrier function. If dysbiosis appears pathogen or fragments of these or toxic agents penetrate the body orchestrating a deep alteration of vital functions such as immune defense, nitric oxide pathways, cell cycle regulation and redox balance.

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 perpetuate a disease-promoting ecosystem.

Oral hygiene is a daily personal protocol for effective delivery of active substances to the tissues of the oral cavity, mainly fluoride and antiseptics. The standard of care in the oral compound is toothpaste used 2-3 times a day.

The test toothpaste including Saliactive® (an olive product, betaine and xylitol) does not contain any antimicrobial agent nor antiseptic. A randomized, double-blind controlled clinical trial in 100 patients will evaluate the efficacy to reverse oral dysbiosis. Microbiota profile through genetic sequenciation of the rDNA16s, inflammatory markers, nitrate reducing bacteria abundance, nitrite/nitrate ratio, pH, plaque and bleeding index will be evaluated at baseline, after 2 months and 4 months of exposure to the assigned composition. Two controls will be analysed, one fluoridated placebo but without the 3 active ingredients olive product, betaine and xylitol (Saliactive®), and a fluoridated commercial toothpaste for gingivitis with zinc citrate. Assignation of the 100 subjects will be randomized and the products are blind for the subjects and the researcher.

Study Timeline

• Study Start: 2021-07-13
• Study First Submitted: 2022-07-07
• Study First Submitted QC: 2022-07-18
• Study First Posted: 2022-07-19
• Primary Completion: 2023-02-28
• Study Completion: 2023-07-15
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-04
• Last Update Posted: 2024-07-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Test product	Test composition Saliactive® (olive product, betaine and xylitol)	Toothpaste including an olive product, betaine and xylitol (Saliactive®).
Placebo product	Placebo	Toothpaste with the same composition as the test product but without olive product, betaine and xylitol.
Control product	Control	Toothpaste marketed for gingivitis with zinc mineral with antimicrobial activity.

Primary Outcome Measures

Name	Time	Method
Oral microbiota profile at baseline and after 4 months	4 months	16s rDNA genetic sequencing
Oral pH at baseline and after 4 months	4 months	pH meter
Nitrite/Nitrate ratio at baseline and after 4 months	4 months	Ionic chromatography
Elastase at baseline at 2 months and at 4 months	4 months	ELISA
Bleeding index at baseline, at 2 months and at 4 months	4 months	Ainamo and Bay bleeding index indicating the percentage of bleeding from 0 (no bleeding) to 100 (maximum bleeding)
Plaque index at baseline, at 2 months and at 4 months	4 months	Tonetti plaque index

Secondary Outcome Measures

Name	Time	Method
Salivary flow rate at baseline, 2 months and at 4 months	4 months	Unstimulated salivary flow rate recovery as per Navazesh

Trial Locations

Locations (1)

Departamento de Estomatología, Facultad de Odontología; 🇪🇸 Granada, Spain