Clinical, Behavioral and Epidemiological Research Branch
Division Of Population and Health Promotion Sciences
Objective:
We are seeking concept clearance for a Request for Applications (RFA) for multi-center clinical trials of immuno- or chemo-therapeutic interventions for management of dental caries.
This research initiative is to sponsor multi-center clinical trials to test immuno- or chemo-therapeutic interventions for management of dental caries. Studies could look at both prevention and treatment of early lesions, in children and adults. If appropriate in terms of maturity of previous clinical research findings, these should be definitive phase 3, randomized, controlled clinical trials powered sufficiently to demonstrate safety and efficacy. This initiative would provide funding initially for one or two phase 3 trials or a larger number of earlier (phase1/phase 2) stage studies.
BACKGROUND
Dental caries is the most common chronic infectious disease in the United States. Although dental caries is a preventable disease, it remains a significant problem in large segments of the population. While caries rates may be declining overall, there is a striking clustering of disease among minority children, the economically underprivileged, older persons, the chronically ill, and institutionalized persons. These long-standing health disparities are becoming more severe.
Although it is well recognized that dental caries is an infectious, communicable disease, it is managed primarily surgically. Management of caries as an infectious disease within a prevention/nonsurgical intervention paradigm is an emerging approach. Current NIDCR support of seven clinical trials in childhood or adult caries and recent research advances form the scientific foundation for and justify this initiative. There is a need to expand this research area as it holds the greatest promise to impact significantly the existing oral health disparities and influence clinical practice. Support for this clinical research theme is provided also by the recent NIH Caries Consensus Conference and the topic clearly meets the criteria formulated by the Advisory Council in January 2002 defining areas of high program priority for clinical studies.
Immuno-therapeutic interventions would likely be in the form of a vaccine or of selective bacterial modification, such as introduction or creation of non-virulent strains. Objectives would be the elimination or significant reduction of cariogenic bacteria in the oral cavity and a significant decrease in dental caries. Chemotherapeutic interventions could utilize a wide range of antimicrobial approaches, including selective bacterial elimination or modification to reduce the concentration of cariogenic organisms, or interventions directed at other components of the cariogenic process, such as acid-induced demineralization or bacterial biofilm formation. Again, objectives would be the elimination or significant reduction of cariogenic bacteria in the oral cavity (if appropriate to the intervention) and a significant decrease in dental caries. It is anticipated that clinical studies would be performed in individuals with high caries rates or at high risk of disease.