Periodontal disease has been recently identified as a risk factor for increased morbidity and mortality for systemic diseases such as pancreatic cancer, cardiovascular disease (atherosclerosis, myocardial infarction, and stroke), and diabetes, as well as for pregnancy complications such as preterm birth. It is well established that periodontal disease results from microorganisms in dental plaque biofilm. Inflammatory reactions initiated by oral bacteria and their components are implicated locally in the pathogenesis of periodontal tissue destruction, and may contribute to the development of systemic disease. While causality has yet to be confirmed, some studies have shown that oral health interventions may impact biological markers of inflammation and disease. The goal of this project is to develop a prescription antimicrobial oral rinse to reduce bacterial bioburden in the oral cavity and combat oral disease and inflammation. Current oral rinse products are either fraught with side effects such as staining and taste alterations that limit their usage to acute settings, or are ineffective. Based on preliminary studies, the oral rinse developed herein is expected to be more effective than currently available prescription products without the side effects. The development of a highly effective oral rinse may have the potential to have a profound impact on public health and achieve significant commercial success. This study is a Fast-Track proposal that combines both Phase I and Phase II studies in one application. The Phase I portion has two Specific Aims: Aim 1. Compound Oral Rinse Formulations for Use in Clinical Trials Aim 2. Evaluate Dose-Response of the Oral Rinse in a Human Clinical Trial of Gingival Inflammation and Investigate Effects on Biological Markers Indicative of Systemic Disease. The Phase II portion has three Specific Aims: Aim 1. Compound Oral Rinse Formulations for Use in Clinical Trials Aim 2. Evaluate the Oral Rinse in a Human Clinical Trial of Gingivitis to Satisfy FDA Requirements and Investigate Effects on Biological Markers Indicative of Systemic Disease.
Public Health Relevance: Recent studies have linked oral bacteria to systemic diseases such as pancreatic cancer, diabetes, stroke and heart disease. Although it has yet to be proven that oral bacteria cause these diseases directly, there is some evidence that dental treatment may improve markers of disease. The development of a safe and effective mouthrinse that could remove harmful oral bacteria and potentially reduce the incidence of disease would have a significant impact on public health.,
Public Health Relevance Statement:, Project Narrative Recent studies have linked oral bacteria to systemic diseases such as pancreatic cancer, diabetes, stroke and heart disease. Although it has yet to be proven that oral bacteria cause these diseases directly, there is some evidence that dental treatment may improve markers of disease. The development of a safe and effective mouthrinse that could remove harmful oral bacteria and potentially reduce the incidence of disease would have a significant impact on public health.,
Project Terms:, 2,4,11,13-Tetraazatetradecanediimidamide, N,N''-bis(4-chlorophenyl)-3,12-diimino-; Acute; Adverse effects; Apoplexy; Applications Grants; Atheroscleroses; Atherosclerosis; Atherosclerotic Cardiovascular Disease; B cell differentiation factor; B cell stimulating factor 2; B-Cell Differentiation Factor-2; B-Cell Stimulatory Factor-2; BCDF; BSF-2; BSF2; BSF2 (B cell stimulating factor 2); Bacteria; Biliary or Urinary Stones; Biologic Marker; Biological Markers; Bleeding; Blood Sample; Blood Tests; Blood specimen; Body Tissues; Buccal Cavity; C-reactive protein; CD62E Antigens; Calculi; Cardiac Diseases; Cardiac Disorders; Cardiac infarction; Cardiovascular Diseases; Causality; Cavitas Oris; Cell Adhesion Molecule E-Selectin; Cerebral Stroke; Cerebrovascular Apoplexy; Cerebrovascular Stroke; Cerebrovascular accident; Chair; Chairman; Chairperson; Chairwoman; Chemistry, Pharmaceutical; Chlorhexidine; Chronic; Clinical; Clinical Research; Clinical Study; Clinical Trials; Clinical Trials, Phase I; Clinical Trials, Phase II; Clinical Trials, Unspecified; Data; Dental; Dental Epidemiology; Dental Hygiene; Dental Plaque; Development; Diabetes Mellitus; Differentiation Factor, B-Cell; Disease; Disease Marker; Disorder; Distal; Doctor of Medicine; Doctor of Philosophy; Dose; Double-Blind Method; Double-Blind Study; Double-Blinded; Double-Masked Method; Double-Masked Study; Drug Evaluation; Drug Formulations; E-Selectin; ELAM-1; Early-Stage Clinical Trials; Endocrinology; Endothelial Adhesion Molecule 1; Endothelial Leukocyte Adhesion Molecule-1; Endotoxins; Engineering; Engineerings; Ensure; Etiology; Evaluation Studies, Drug; Exposure to; Formulation; Formulations, Drug; Gingiva; Gingival; Gingival Indexes; Gingivitis; Goals; Grant; Grant Proposals; Grants, Applications; Gustation; HPGF; Head and Neck, Buccal Cavity; Head and Neck, Thyroid; Health; Health Sciences; Heart Diseases; Hematologic Tests; Hematological Tests; Hematology Testing; Hemorrhage; Hepatocyte-Stimulating Factor; Human; Human, General; Hybridoma Growth Factor; I- element; IFN-beta 2; IFNB2; IL-1; IL-6; IL1; IL6 Protein; INFLM; Incidence; Industry; Inflammation; Inflammatory; Interleukin 6 (Interferon, Beta 2); Interleukin I; Interleukin-1; Interleukin-6; Intervention; Intervention Strategies; Investigational New Drug Application; Investigators; Iodine; LDL; LDL Cholesterol; LDL Cholesterol Lipoproteins; LECAM-2; LPS; Laboratories; Lead; Leukocyte Endothelial Cell Adhesion Molecule 2; Link; Lipopolysaccharides; Lipoproteins, LDL; Listerine; Low Density Lipoprotein Cholesterol; Low-Density Lipoproteins; Lymphocyte-Stimulating Hormone; M.D.; MGI-2; Macrophage Cell Factor; Malignant Pancreatic Neoplasm; Malignant neoplasm of pancreas; Man (Taxonomy); Man, Modern; Measurement; Measures; Medicinal Chemistry; Metabolism and Endocrinology; Method LOINC Axis 6; Methodology; Methods; Microbial Biofilms; Microorganisms, General; Molecular; Molecular Marker; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Mouth; Mouth Diseases; Myeloid Differentiation-Inducing Protein; Myocardial Infarct; Myocardial Infarction; Oral; Oral Cavity Disease; Oral Cavity Disorder; Oral Disease; Oral Disorder; Oral Health Epidemiology; Oral Hygiene; Oral Microbiology; Oral cavity; Oral health; Outlines (PT); Outlines [Publication Type]; PBO; Pancreas Cancer; Pancreatic Cancer; Parodontosis; Pathogenesis; Pathway interactions; Patients; Pb element; Periodontal Diseases; Periodontal Infection; Periodontic; Periodontic specialty; Periodontics; Ph.D.; PhD; Pharmaceutic Chemistry; Pharmaceutical Agent; Pharmaceutical Chemistry; Pharmaceuticals; Pharmacologic Substance; Pharmacological Substance; Phase; Phase 1 Clinical Trials; Phase 2 Clinical Trials; Phase I Clinical Trials; Phase I Study; Phase II Clinical Trials; Placebo Control; Placebos; Plasmacytoma Growth Factor; Play; Pregnancy Complications; Premature Birth; Preterm Birth; Prevention; Prevention Measures; Principal Investigator; Procedures; Process; Production; Prophylactic treatment; Prophylaxis; Proteins, specific or class, C-reactive; Protocols, Treatment; Public Health; Quality Control; RGM; Randomized; Reaction; Regimen; Regulation; Reporting; Research; Research Personnel; Researchers; Risk Factors; Role; Safety; Science; Sham Treatment; Signature Molecule; Staining method; Stainings; Stains; Stone; Stroke; Study Subject; System; System, LOINC Axis 4; Systemic disease; T Helper Factor; Taste; Taste Perception; Technology; Testing; Texas; Thyroid; Thyroid Function Tests; Thyroid Gland; Thyroid Gland Function Tests; Time; Tissues; Toxicology; Treatment Protocols; Treatment Regimen; Treatment Schedule; Treatment Side Effects; Universities; Vascular Accident, Brain; anti-microbial; antimicrobial; atheromatosis; atherosclerotic vascular disease; base; beta-Lipoprotein Cholesterol; beta-Lipoproteins; biofilm; biomarker; blood loss; brain attack; cardiac infarct; cardiovascular disorder; cerebral vascular accident; chemical reaction; clinical efficacy; clinical investigation; combat; commercialization; coronary attack; coronary infarct; coronary infarction; dental health; design; designing; diabetes; disease causation; disease etiology; disease/disorder; disease/disorder etiology; disorder etiology; dosage; double-blind placebo controlled trial; double-masked controlled study; double-masked controlled trial; drug quality; early onset; efficacy trial; endothelial leukocyte adhesion molecule; experience; heart attack; heart disorder; heart infarct; heart infarction; heavy metal Pb; heavy metal lead; improved; indexing; interferon beta 2; interventional strategy; lymphocyte activating factor; meetings; microbicidal; microbicide; microorganism; mouth disorder; novel; oral bacteria; oral epidemiology; oral flora; oral plaque; outlines (document); pathogen; pathway; periodontal disorder; periodontium disease; periodontium disorder; phase 1 study; phase 1 trial; phase 2 study; phase 2 trial; phase I trial; phase II trial; premature childbirth; premature delivery; preterm delivery; prevent; preventing; primary outcome; professor; protocol, phase I; protocol, phase II; public health medicine (field); public health relevance; quality assurance; randomisation; randomization; randomly assigned; response; sham therapy; side effect; social role; stroke; study, phase II; success; therapy adverse effect; thyroid function; tool; treatment adverse effect
