Carnosine Supplementation on Quantity/Quality of Oral Salivae.

Oral Diseases Clinical Trial

— PHoral  

Official title:

PHoral: Effects of Carnosine Supplementation on Quantity/Quality of Oral Salivae in Healthy Volunteer and in Subjects Affected by Common Oral Pathologies.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04295525
• Other study ID #: P0A.20.20
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: December 1, 2022

Study information

• Verified date: May 2022
• Source: University of Milan
• Contact: Dino Re, MD
• Phone: +39-0254176231
• Email: dino.re[@]unimi.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to elucidate the mutual relationship between salivae characteristics and oral microbiome and to compare them with common oral disease; furthermore, by using specific bioinformatic tools to analyse the data, the potentials of Carnosine in preventing/treating oral diseases and its mechanism of action will be addressed by using quantitative proteomics.

Description:

The pH of the oral cavity is a synthetic parameter that underlies a multifactorial process of continuous adjustment that includes the effect of salivae as a buffer and the contribution of the oral cavity microbiome. In some diseases of the oral cavity an alteration of these adjustment mechanisms is supposed to alter the normal flow of salivae and, consequently, the pH and the oral microbiome with the expansion of potentially pathogenic strains such as e.g. streptococcus viridans.

Carnosine (Car) is an endogenous dipeptide, composed of β-alanine and L-histidine, that was originally discovered in larger amounts in skeletal muscle of some vertebrates, including humans, showing a greater dependence on non-oxidative forms of energy metabolism. This peculiar association with muscular tissue and its pH-buffering properties has led to associate Car with the intracellular acid-base homeostasis of muscles. More recently, the physiological role of Car has been expanded beyond the intracellular buffering properties, supporting a role in sarcoplasmic Ca2+ regulation and neutralisation of reactive oxygen species (ROS). It is well known that ROS induce the formation of reactive electrophilic carbonyl species by reacting with lipids and sugars which, in turn, react with proteins forming irreversible adducts (AGEs, ALEs and EAGLEs) and cross-links that may affect the cardiovascular wall matrix that becomes less distensible, especially during the ageing process and/or diseases. Thus it is thought that Car and, indeed, other histidine-containing peptide (HCD), may prevent chronic diseases via their anti-inflammatory, anti-oxidative, anti-glycating, anti-ischaemic and chelating properties. Furthermore, the localisation of Car in other tissues such as brain, olfactory bulb, heart, stomach, pancreas, kidney has suggested further potential uses in preventing e.g. neurodegenerative disorder and cognitive function or the development of type II diabetes.

The oral microbiome (OM) is a relevant part of the whole human MO since it contains several different niches, with distinct microbial communities, colonising the oral cavity (OC), including not only bacteria but also fungi, viruses, archaea and protozoa. These communities form a complex ecological system that influences OC and systemic health. Indeed the prevalent oral diseases (OD), namely dental caries and periodontal diseases, are believed to be microbiota-related. Furthermore, several evidences support the theory that many systemic diseases are associated with an altered OM, among these the most frequently associated diseases are metabolic, such as diabetes, cardiovascular and oncological ones. For their prevalence worldwide, among OD, periodontal infection, including gingivitis and chronic periodontitis, is possibly the most prevalent human microbial diseases (HMD).

In order to protect the OC from HMD, in the present project Car has been chosen as a possible preventive and/or therapeutic principle for its aforementioned multiple biological effects. Thus the safety and efficacy of AqualiefTM (Metis Healthcare s.r.l., Milano, Italy) a 400 mg mucoadhesive oral tablet (13 x 4 mm), that recognise Car as main ingredient, will be tested on healthy volunteer and in subjects affected by common OD.

The main objectives of this protocol are to estimate the quantity/quality of oral salivae and OM in healthy volunteer and in patients affected by common OD, before and after 7 days of treatment with AqualiefTM, 1 tablet twice. The characteristics of oral salivae (Sal) that will be studied are:

a - unstimulated and stimulated (paraffin-activated) salivary flow rates, pH and buffering power; b - quantitative proteomics (QP), on selected targets, representing the main metabolites/components of OM.

By matching Sal characteristics with OM and comparing them with OD, it is expected to elucidate their mutual relationship; furthermore, by using specific bioinformatic tools to analyse the data, the potentials of Car in preventing/treating OD and its mechanism of action will be addressed by using QP.

The study will take place at the Odontoiatric University Clinic (OUC), Istituto Stomatologico Italiano (ISI) of Milan, Italy, in a prospective, randomised, double-blind, placebo-controlled fashion.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 1, 2022
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria for Oral Diseased subjects:

• dental erosions (De)

• caries (Ca)

• périodontopathies (Pe)

Exclusion Criteria for both:

• allergies/intolerances to the consumption of Carnosine

• taking other food supplements

• any type of drug treatment (interview)

• smoking

• pregnancy/lactation

• any systemic diseases such as cardiovascular and respiratory, diabetes mellitus, HIV infection, or inflammatory conditions causing non-plaque dependent OD.

Related Conditions & MeSH terms

• Mouth Diseases
• Oral Diseases

Intervention

Dietary Supplement:
• 400 mg mucoadhesive oral tablet
AqualiefTM (Metis Healthcare s.r.l., Milano, Italy)
• placebo mucoadhesive oral tablet
placebo

Locations

Country	Name	City	State
Italy	Department of Biomedical, Surgical, and Dental Sciences, Istituto Stomatologico Italiano, Aesthetic Dentistry, School of Dentistry, University of Milan, Milan, Italy.	Milan

Sponsors (1)

Lead Sponsor	Collaborator
University of Milan

Country where clinical trial is conducted

Italy, 

References & Publications (10)

Abranches J, Zeng L, Kajfasz JK, Palmer SR, Chakraborty B, Wen ZT, Richards VP, Brady LJ, Lemos JA. Biology of Oral Streptococci. Microbiol Spectr. 2018 Oct;6(5). doi: 10.1128/microbiolspec.GPP3-0042-2018. Review. — View Citation

Boldyrev AA, Aldini G, Derave W. Physiology and pathophysiology of carnosine. Physiol Rev. 2013 Oct;93(4):1803-45. doi: 10.1152/physrev.00039.2012. Review. — View Citation

Ciulla MM, Paliotti R, Carini M, Magrini F, Aldini G. Fibrosis, Enzymatic and Non-Enzymatic Cross-Links in Hypertensive Heart Disease. Cardiovasc Hematol Disord Drug Targets. 2011;11(2):61-73. Review. — View Citation

de Almeida Pdel V, Grégio AM, Machado MA, de Lima AA, Azevedo LR. Saliva composition and functions: a comprehensive review. J Contemp Dent Pract. 2008 Mar 1;9(3):72-80. Review. — View Citation

Dolan E, Saunders B, Harris RC, Bicudo JEPW, Bishop DJ, Sale C, Gualano B. Comparative physiology investigations support a role for histidine-containing dipeptides in intracellular acid-base regulation of skeletal muscle. Comp Biochem Physiol A Mol Integr — View Citation

Grassl N, Kulak NA, Pichler G, Geyer PE, Jung J, Schubert S, Sinitcyn P, Cox J, Mann M. Ultra-deep and quantitative saliva proteome reveals dynamics of the oral microbiome. Genome Med. 2016 Apr 21;8(1):44. doi: 10.1186/s13073-016-0293-0. — View Citation

Holtfreter B, Albandar JM, Dietrich T, Dye BA, Eaton KA, Eke PI, Papapanou PN, Kocher T; Joint EU/USA Periodontal Epidemiology Working Group. Standards for reporting chronic periodontitis prevalence and severity in epidemiologic studies: Proposed standard — View Citation

Marsh PD, Do T, Beighton D, Devine DA. Influence of saliva on the oral microbiota. Periodontol 2000. 2016 Feb;70(1):80-92. doi: 10.1111/prd.12098. Review. — View Citation

Menon K, Mousa A, de Courten B. Effects of supplementation with carnosine and other histidine-containing dipeptides on chronic disease risk factors and outcomes: protocol for a systematic review of randomised controlled trials. BMJ Open. 2018 Mar 22;8(3): — View Citation

Zhang Y, Wang X, Li H, Ni C, Du Z, Yan F. Human oral microbiota and its modulation for oral health. Biomed Pharmacother. 2018 Mar;99:883-893. doi: 10.1016/j.biopha.2018.01.146. Epub 2018 Feb 20. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effects on oral pH.	Any change of oral pH from basal.	7 days
Primary	Saliva Production unstimulated.	Change of oral saliva production, unstimulated.	7 days
Primary	Saliva Production stimulated.	Change of oral saliva production, stimulated.	7 days