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

NCT ID: NCT05463484

Last Updated: 2024-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-13
• Study Completion Date: 2023-07-15

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.

Conditions

Oral Dysbiosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

Test product

Toothpaste including an olive product, betaine and xylitol (Saliactive®).

Group Type: EXPERIMENTAL

Test composition Saliactive® (olive product, betaine and xylitol)

Intervention Type: DRUG

Fluoridated toothpaste with Saliactive®.

Placebo product

Toothpaste with the same composition as the test product but without olive product, betaine and xylitol.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Fluoridated toothpaste without Saliactive®.

Control product

Toothpaste marketed for gingivitis with zinc mineral with antimicrobial activity.

Group Type: ACTIVE_COMPARATOR

Control

Intervention Type: DRUG

Commercial Fluoridated toothpaste for gingivitis with zinc citrate.

Interventions

Test composition Saliactive® (olive product, betaine and xylitol)

Fluoridated toothpaste with Saliactive®.

Intervention Type: DRUG

Placebo

Fluoridated toothpaste without Saliactive®.

Intervention Type: DRUG

Control

Commercial Fluoridated toothpaste for gingivitis with zinc citrate.

Intervention Type: DRUG

Other Intervention Names

Saliactive®; Placebo fluoridated toothpaste without the test composition; Control commercial Fluoridated toothpaste for gingivitis with zinc citrate.

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universidad de Granada

OTHER

Sponsor Role: collaborator

Mucosa Innovations, S.L.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francisco Luis Mesa Aguado

Role: PRINCIPAL_INVESTIGATOR

Departamento de Estomatología, Facultad de Odontología

Locations

Departamento de Estomatología, Facultad de Odontología

Granada, , Spain

Countries

Spain

References

Tonetti MS. The future of periodontology: new treatments for a new era. J Int Acad Periodontol. 2002 Jul;4(3):110-4.

Reference Type: BACKGROUND

PMID: 12670090 (View on PubMed)

Ainamo J, Bay I. Problems and proposals for recording gingivitis and plaque. Int Dent J. 1975 Dec;25(4):229-35.

Reference Type: BACKGROUND

PMID: 1058834 (View on PubMed)

Navazesh M. Methods for collecting saliva. Ann N Y Acad Sci. 1993 Sep 20;694:72-7. doi: 10.1111/j.1749-6632.1993.tb18343.x. No abstract available.

Reference Type: BACKGROUND

PMID: 8215087 (View on PubMed)

Barbadoro P, Ponzio E, Coccia E, Prospero E, Santarelli A, Rappelli GGL, D'Errico MM. Association between hypertension, oral microbiome and salivary nitric oxide: A case-control study. Nitric Oxide. 2021 Jan 1;106:66-71. doi: 10.1016/j.niox.2020.11.002. Epub 2020 Nov 10.

Reference Type: BACKGROUND

PMID: 33186726 (View on PubMed)

Bescos R, Ashworth A, Cutler C, Brookes ZL, Belfield L, Rodiles A, Casas-Agustench P, Farnham G, Liddle L, Burleigh M, White D, Easton C, Hickson M. Effects of Chlorhexidine mouthwash on the oral microbiome. Sci Rep. 2020 Mar 24;10(1):5254. doi: 10.1038/s41598-020-61912-4.

Reference Type: BACKGROUND

PMID: 32210245 (View on PubMed)

Other Identifiers

02-2021

Identifier Type: -

Identifier Source: org_study_id