Current Clinical Research

Dr. Beatty in labA clinical trial is a form of clinical research that seeks to evaluate the risks and benefits of a drug, device, or other types of treatment. Clinical trials in dentistry are conducted to find better ways to prevent, diagnose, or treat oral conditions such as dental decay, periodontal disease, or the oral side effects of systemic diseases such as dry mouth. Clinical trials and studies conducted by our researchers have been funded by the National Institutes of Health (NIH), private foundations, and industry. Examples of current clinical trials and studies being conducted by COD faculty are listed below. Please visit our completed clinical research

Dr. Thyagaseely Premaraj and Dr. Sundaralingam Premaraj
Title: Shift in Species Composition of Supra gingival Microbiome as a Risk factor in Dental Caries – a comparative study with braces/Invisalign® treatment
Funding agency: Align Technology 
Enamel decalcification is elevated with orthodontic therapy (braces) due to bacterial populations that accumulate within the plaque environment. Disturbances in bacterial community are likely cause for opportunistic pathogens. Invisalign® therapy may be a healthier alternative to avoid such side effects as microbial community may not be altered during treatment. Our long-term goal is to understand how changes in the bacterial community can initiate and progress to development of dental caries. Monitoring bacterial changes would identify potential bio markers for caries initiation. Using metagenomic approaches, our approach is to measure and compare the temporal changes in the supra gingival plaque microbiota before and after introduction of braces or invisalign® to the patient. Our central hypothesis is that introducing braces cause shifts in the bacterial community composition in supra plaque that ultimately leads to enamel decalcification and caries development. We will test this hypothesis through the following specific aims: 1) to determine bacterial composition of supra gingival plaque before and 6 months after introduction of braces/Invisalign®. 2) to determine quantity changes of total bacteria in plaque. Supra gingival samples will be collected from patients before they undergo orthodontic therapy with either braces or Invisalign®. Plaque samples will be collected from the same individuals after 6 months into treatment to compare the microbial profiles. Metagenomic approaches will be utilized for identification of bacterial species since most of the species that comprise this community have not been successfully cultivated. Culture based analysis are likely to miss significant portion of the microbes and unlikely represent the actual changes. The relative abundances of bacteria will be measured using pyrosequencing of 16S rRNA tags and absolute number of suspect organisms quantified using real-time PCR. This will be the first temporal study to monitor bacterial community changes in individuals with braces/Invisalign® using metagenomic approaches. 
Dr. Mark Beatty
Title: Viscoelastic Properties of Human Facial Skin
Funding Agency: Veterans Administration Rehabilitation R & D
Many military combat injuries involve the head and neck. Often these injuries result in losses of noses, eyes, ears or jaws. These missing facial structures are no longer able to function, and they produce deformities in facial appearance. When lost facial structures cannot be corrected surgically, they are replaced by artificial prostheses. Head and face prostheses should look and feel like natural skin, but unfortunately present-day materials do not always permit a realistic duplication of lost facial structures. Also, many prostheses demonstrate short lifetimes, as they fade and harden, sometimes within a period of only a few months. Consequently, nearly 25% of facial prostheses must be replaced each year. The long-term goal of this research is to develop a new generation of materials that will produce facial prostheses that look and feel like human facial skin. In order to achieve this goal, baseline information is needed to establish "gold standards" towards which future improvements in materials may be targeted. Therefore, the objective of this pilot project is to provide this baseline information by measuring facial skin elasticity in a human population. The project is designed to include equal numbers of participants from four racial groups (Asian, black, white, Hispanic), both genders and three age groups between 18 and 70 years. Facial skin elasticity (which yields information regarding the feel of skin) will be measured by a device that is placed against the skin and applies suction for 18 seconds. When the suction stops, the device measures how the skin recovers and this provides information regarding the skin's elastic recovery (or feel). Measurements will be made at three locations - forehead, cheek and chin. The results will be analyzed to determine whether skin elasticity is different based on race, age and facial location. Also, a statistical procedure (clustering analysis) will analyze the data to identify certain skin elastic properties that characterize the group of human subjects included in this study. This information is critical for future research designed to improve polymers (plastics) and additives that will better replicate the appearance and feel of human facial skin.
Dr. Ted Mikuls (UNMC College of Medicine) and Dr. Jeffrey Payne
Title: Periodontal Disease and P. gingivalis in Rheumatoid Arthritis
Funding Agency: American College of Rheumatology Research and Education Foundation
Periodontitis (PD) has been postulated to be a risk factor for the onset and progression of rheumatoid arthritis (RA). Recent reports have suggested that infection with Porphyromonas gingivalis (P. gingivalis), a major pathogen in PD, could play a pivotal role in autoantigen presentation and the development of anti-citrullinated protein antibody (ACPA) in RA. This is important since ACPA-positivity is associated with poor RA outcomes and these autoantibodies are thought to play a direct pathogenic role in the disease. Previous studies examining the associations of PD and/or P. gingivalis have been small in size and have been limited by inadequate control for important confounding factors. In the largest study to date and the first to include simultaneous measurements of oral health and P. gingivalis serology in RA patients, we will examine: 1) The associations of PD and/or P. gingivalis with RA risk and disease severity, accounting for the major factors thought to confound these relationships. We will examine whether these associations are modified by the presence of genetic risk factors, namely HLA-DRB1 alleles encoding the shared epitope (SE); 2) The longitudinal associations of PD and/or P. gingivalis with the development of RA among military personnel with banked sera from the Department of Defense Serum Repository (DoDSR); 3) Whether there are novel proteins expressed by P. gingivalis that drive autoimmunity in RA and whether immune responses to these antigens predict the future RA development in the DoDSR; and 4) The association of P. gingivalis with the presence of RA-related autoantibody among first-degree relatives of RA-probands (RA-free at assessment), studies that will complement those performed using the DoDSR. Our hypothesis is that PD is a risk factor for the onset and progression of ACPA-positive RA in genetically susceptible individuals, a risk that is conferred primarily through infection with P. gingivalis. The specific aims of this study are: 1) To confirm the previously reported associations of PD with RA in a large well-defined patient population, and in the process show that the associations of PD with RA are primarily due to infection with P. gingivalis; and 2) To examine whether PD and antibody to P. gingivalis are risk factors for the future development of RA and to examine whether antibody to P. gingivalis is more common in individuals at high risk for developing RA compared to individuals at lower risk for developing RA. To address these aims, we have gathered an international multidisciplinary research team with extensive expertise in the epidemiology and immunology of RA and PD with access to important and highly unique patient populations that will allow for the first comprehensive examination of the association of PD and P. gingivalis infection with RA. Relevance: This study will provide crucial insight into the interrelationship of PD, P. gingivalis, and RA and in the process provide valuable information on disease pathogenesis in RA. It is anticipated that results from this study and those to follow, will ultimately lead to new avenues in the treatment and prevention of RA.
Dr. Julie Stoner (University of Oklahoma Health Sciences Center) and Dr. Jeffrey Payne
Title: Examining Multilevel Associations in Dental Research
Funding Agency: National Institute of Dental and Craniofacial Research (NIH
In the United States in 2002, approximately 7.8 million women aged 50 and over had osteoporosis of the hip and an additional 21.8 million had low bone mass or osteopenia of the hip and were at risk for developing osteoporosis. Data, largely from cross-sectional studies, suggest that osteoporosis is associated with increased tooth loss, alveolar bone loss, and periodontal attachment loss. Oral health research studies investigating progression of periodontal disease and alveolar bone loss often involve multilevel, nested measures at the tooth-site level within subjects followed longitudinally over time. Disease processes may vary within a subject's mouth or over time within a subject and disease processes may differ between subjects. Typically, regression modeling approaches do not distinguish among effects of chronic or patient-level associations and associations with acute changes over time or spatial variation within a mouth. A better understanding of the multilevel disease processes could lead to more effective clinical follow-up procedures and more effective therapies. Our long-term goal is to slow the progression of alveolar bone loss and clinical attachment loss in post-menopausal osteopenic women with periodontitis. The specific aims of this proposal are to: 1) Develop computing macros, based on generalized estimating equation methodology, that can be implemented in SAS and R for fitting and statistically comparing separate within-mouth, across-time, and between-subject effects in correlated data regression models; 2) Through simulation, develop guidelines for study design, including sample size, to ensure adequate power to detect different within-mouth, across-time, and between-subject effects; and 3) Apply the developed regression analysis methodology to existing data from our recently-completed National Institute of Dental and Craniofacial Research (NIDCR)-funded (R01DE012872) randomized double-blind, placebo-controlled clinical trial of sub-antimicrobial dose doxycycline (SDD) in postmenopausal osteopenic women with moderate to advanced periodontitis. The proposed analyses will utilize existing oral radiographic and clinical periodontal measures, as well as serum inflammatory biomarker and systemic bone mineral density measurements, from the 128 women who were enrolled in the 2-year clinical trial. The objectives of the secondary data analyses are to identify oral and systemic factors associated with alveolar bone loss and periodontitis progression over a 2-year period, distinguishing among effects of chronic or patient-level associations and associations with acute changes over time or spatial variation within a mouth. A better understanding of the complex, multilevel associations among oral and systemic factors associated with alveolar bone loss and periodontitis progression could lead to new clinical follow-up protocols and therapeutic approaches that will improve the oral health of this population.  
Dr. Amy Killeen and Dr. Richard Reinhardt
Title: Local Minocycline to Reduce Future Inflammation and Bone Loss in Periodontal Maintenance Patients
Funding Agency: DH Reinhardt Scholar Fund, Nebraska Dental Association (NDA) Foundation Grant,
Dr. Mick and Mary Dragoo through the NU Foundation’s Periodontal Development Fund 
The over-arching goal of this application is to initiate a program to involve undergraduate dental students and their patients in clinical research to evaluate the efficacy of dental therapy. Specifically, the purpose of this study is to determine the effect of local application of minocycline microspheres on the periodontal inflammation and bone loss prevention in patients diagnosed with moderate-severe chronic periodontitis on periodontal maintenance in the undergraduate clinic. Few studies evaluating locally-applied minocycline during periodontal maintenance therapy have been reported even though the drug is commonly used in this protocol. A 6-month treatment study by Meinberg et al. (2002), demonstrated that in moderate-to-advanced chronic periodontitis patients, scaling and root planing with subgingival minocycline resulted in improved pocket depths and less frequent bone height loss over one year than conventional periodontal maintenance. The prevention of bone loss and inflammation is key to maintaining teeth in function and comfort for the patient’s lifetime. Patients from the UNMC College of Dentistry (and eventually Creighton University School of Dentistry) undergraduate periodontal clinic, who are already enrolled in periodontal maintenance therapy, will be recruited to participate in this study. The selected patients will continue their periodontal maintenance care but will be placed into either the test group (receiving minocycline in a periodontally inflamed pocket along with subgingival mechanical debridement) or the control group (receiving subgingival mechanical debridement alone). Radiographs will be taken at baseline and at the study’s completion (24 months) to obtain bone loss data, and periodontal measurements and gingival crevicular fluid (GCF) will be used to monitor markers of inflammation and bone resorption. The hypothesis to be tested in this clinical trial is that the use of minocycline at baseline and 6 month intervals in conjunction with subgingival mechanical debridement will reduce interproximal bone height loss and periodontal inflammation more than mechanical debridement alone.