Clinical Studies

Predicting Caries Lesion Patterns and Trajectories in Underserved Children, from Infancy to Early Adolescence, in Primary Healthcare Settings​

Principal Investigator: Dr. Margarita Fontana, DDS, MS, PhD​
Indiana Site Principal Investigator: Dr. Anderson Hara, DDS, MS, PhD

​Study Funded by: NIDCR/NIH (U01-DE021412-09)

This collaborative, innovative and high impact interdisciplinary project (continuing renewal of our ongoing caries risk study U01-DE021412-11) provides a unique opportunity to assess U.S. children over time culminating with much needed access and focus on adolescence- a life stage in which people have persistent caries problems over the last few decades, is challenging to recruit, and has been largely neglected in oral health research, practice, and policy. The relevance, impact, and significance of the project is that it will result in the creation of critically important and novel prediction models, and understanding of relationships among oral and systemic health risk factors and comorbidities into early adolescence, which is essential to designing future implementation efforts to target efficient, cost-effective, preventive, person-centered care for dental caries, as well as collaborative interprofessional care to reduce disparities and improve adolescents health. ​​

Evaluation of the efficacy and safety of a loop stretchable dental floss in controlling gingivitis and supragingival plaque removal during thirty days.

Principal Investigator: Dr. Ana G. Gossweiler
Study Funded by: Loops, LLC

Interproximal plaque control is the most efficient method to prevent inflammation at the papillary gingival unit. This type of cleaning cannot be achieved with tooth brushing alone; flossing needs to be incorporated into the oral hygiene procedures to achieve and maintain the health of the interdental papilla. Over the years, different types of materials have been used to produce dental floss, including nylon, PTFE, silk, and UHMUPE, among others. Even though all these dental flosses are effective in removing dental plaque, the users' subjective preference is based on the surface roughness and tensile strength. Among the user's preferences, the handling of the floss also has to be considered; loop floss provides a new design that appears to be easy to use and improves the user's manual dexterity. This study aims to evaluate the efficacy and safety of a stretchable floss controlling gingivitis and supragingival plaque removal between control and experimental groups in thirty days.

A randomized, double-blind, placebo controlled, 2-arm multicenter phase 3 study to assess the efficacy and safety of ianalumab in patients with active Sjögren’s syndrome (NEPTUNUS-1)​

Principal Investigator: Dr. Domenick Zero, DDS, MS​
Study Funded by: NOVARTIS​

Sjögren's syndrome is a slowly progressing systemic autoimmune disease, with unknown etiology. The disease is primarily characterized by lymphocytic infiltration in the exocrine glands, mainly in the lachrymal and salivary glands, with their consequent impaired secretory function. The most prominent symptoms present in the majority of patients include dry eyes, dry mouth, fatigue and joint pain (Mariette et al 2015). There is no approved therapy for patients with active Sjögren’s. The standard of care (SoC) is limited to a symptomatic treatment with topical treatments like ocular gels, ointments and artificial tears for ocular dryness, and salivary stimulants or saliva substitutes for oral dryness. In selected patients with active systemic disease, corticosteroids, conventional disease-modifying antirheumatic drugs (DMARDs), intravenous immunoglobulins or biologics may be used (Ramos-Casals et al 2020). No systemic therapy has proven efficacious till now, and no pharmacologic intervention is effective against the severe, disabling fatigue.

The purpose of this study is to demonstrate the clinical efficacy, safety and tolerability of ianalumab (VAY736) 300 mg administered monthly compared to placebo in patients with active Sjögren’s syndrome. After completion of the 52-week blinded treatment period in this study, participants may enter a subsequent, separate, optional extension study. Details of the study will be provided in a separate protocol. In addition, in patients who prematurely discontinue the core study treatment or do not enter extension study, long-term efficacy and safety will be assessed in a post-treatment follow-up.

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A Randomized, Double Blind, Placebo-Controlled Single Center Phase 2 Pilot Study to Assess the Safety and Efficacy of Off-label Subcutaneous Administration of Erenumab-aooe in Patients with Temporomandibular Disorder​

Principal Investigator: Dr. Domenick Zero, DDS, MS​
Study Funded by: Amgen​

Aimovig® [erenumab (EREN)] is a first in class FDA-approved human monoclonal antibody (UmAb) for the prevention of migraine in adults. It selectively targets and blocks the calcitonin gene-related peptide (CGRP) receptor, disrupting a key component of migraine pathophysiology (Hargreaves & Olesen, 2019). Several studies have provided evidence of the safety and efficacy of Aimovig® in reducing the frequency of migraine compared to placebo (Goadsby et al., 2017; Tepper et al., 2017). Furthermore, an open-label longer-term study found that Aimovig® was safe and well-tolerated with a safety profile consistent with shorter-term placebo-controlled studies (Ashina et al., 2020), through 5-years of treatment. Aimovig® has rapidly become a widely accepted prescription drug for the prevention of migraines, including episodic migraine and chronic migraine (CM) along with other anti-CGRP monoclonal antibody-based therapies (Yuan et al., 2019). 

CM is thought to originate within the trigeminovascular pathway (TGV) (Noseda & Burstein, 2013). TMD is also considered to originate within the TGV (de Leeuw, 2018). Thus, our working hypothesis is that a CGRP receptor antagonist for treatment of CM will also be effective in reducing TMD pain and related symptoms. To test this hypothesis, we will apply several validated measures: Brief Pain Inventory (BPI) (Kean et al., 2016); PEG (Pain, Enjoyment, General Activity) Scale (Krebs et al., 2009); an assessment of daily pain medication; Patient Global Impression of Change (PGIC) (Kroenke et al., 2018); Jaw Function Limitation Scale (JFLS) (Ohrbach et al., 2008); Patient Health Questionnaire (PHQ-4) (Kroenke et al., 2009); and Somatic Symptom Scale (SSS-8) (Toussaint et al., 2017).​

The purpose of this proof of concept study is to evaluate the safety and efficacy of the off-label use of Aimovig® (EREN) in reducing Temporomandibular Disorder (TMD) pain compared to placebo. 

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A Phase 2 randomized, double-blind, active-controlled multi-center clinical trial to assess the safety and the anti-caries efficacy of COL 101 (arginine) non-fluoride dentifrices with 1.5%, 4.0% and 8.0% arginine each in comparison with 0.24% sodium fluoride (1100 ppm F) dentifrice control in 10 to 14 year-old children.​

Principal Investigator: Dr. Domenick Zero, DDS, MS​
Study Funded by: Colgate-Palmolive​

Traditional caries prevention strategies have focused on making the tooth stronger by allowing for the replacement of the hydroxyl ions in hydroxyapatite-forming fluorapatite and maximizing the stability of the tooth mineral. This mode of action has a favorable outcome on mineral balance. Fluoride modulates calcium phosphate chemistry at the tooth surface with little to no effect on causative plaque bacteria (Santarpia et al., 2014)1 • An alternative preventive strategy to address the cause has been identified through the use of arginine toothpaste to mimic our mouths' natural defense mechanism against caries. Unlike fluoride, arginine is utilized by beneficial bacteria to produce alkali, which helps maintain a pH favoring mineral repair and creates an environment that disfavors cariogenic bacteria and their deleterious activities.  ​

​Arginine has a good safety profile and is currently marketed in the United States (US) as an ingredient in dentifrice. Proven clinical benefits include the reduction of dentin hypersensitivity. There has been no observed pattern of adverse events (AEs) associated with its regular use. This study is intended to evaluate anti-caries efficacy of COL 101 (arginine) non-­fluoride dentifrices with 1.5%, 4.0% and 8.0% arginine each in comparison with 0.24% sodium fluoride ( 1100 ppm F) dentifrice control in 10-14 year old children for a period of one year. The outcome of this study may lead to an alternative method of caries prevention. 

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Comparison of theremineralization potential of an optimized fluoride dentifricewith a control fluoride dentifrice using an in situ caries model.

Principal Investigator: Dr. Domenick Zero
Study Funded by: Haleon

The purpose of this study is to compare the remineralization potential of an optimized fluoride dentifrice to a control fluoride dentifrice in an in situ caries model.

This will be a double blind, single center, 3-way crossover design study. Two to three days before the start of each treatment period the subjects will have their teeth cleaned to remove all accessible plaque and calculus and will be provided with a non-fluoride dentifrice to use until their next visit. At the beginning of each testing period, two gauze-covered 4 mm round partially demineralized bovine
enamel specimens will be placed in the buccal surface of two posterior denture teeth (the specimen site may extend into the buccal flange area, if needed) of the same side of the partial denture. Once specimens are placed, subjects will wear their partial dentures twenty-four hours a day and use their
assigned toothpaste twice daily, as instructed, until their next visit. Specimens will be removed after two weeks, and the subjects will undergo at least a four- to five-day washout period followed by another cleaning and two to three day lead in period. This process will be repeated until all subjects have used all three test products. Changes in the mineral content of the enamel specimens will be assessed using surface microhardness (SMH) and transverse microradiography (TMR). Enamel fluoride uptake (EFU) will be determined using the microdrill enamel biopsy technique. In addition, the net acid resistance (NAR) and the comparative acid resistance (CAR) of the remineralized enamel specimens will be determined.

A Randomized, Examiner Blind, Crossover, in situ Erosion Study to Investigate the Efficacy of an Experimental Dentifrice in Remineralization of Softened Enamel Compared to Placebo and Reference Dentifrices.

Principal Investigator: Dr. Anderson Hara
Study Funded by: Haleon

This study will investigate the ability of an experimental dentifrice containing 1150ppm fluoride to remineralize acid-softened dental enamel and help prevent further demineralization compared to a 0ppm fluoride placebo dentifrice and a marketed, fluoride-containing dentifrice (Reference Dentifrice). The study will utilize an established in situ model where partially demineralized enamel specimens will be placed in a dental palatal appliance, treated intra orally then allowed to remineralize in situ for 4 and 12 hours. Efficacy will be evaluated through laboratory measurement of the surface microhardness recovery (SMHR), relative erosion resistance (RER), acid resistance ratio (ARR) and the enamel fluoride uptake (EFU).

Primary Objective:
To investigate the efficacy of an experimental dentifrice containing 1150 ppm fluoride and 5% KNO3 to enhance remineralization of enamel compared to a placebo dentifrice (0ppm fluoride) after 4 hours of intra-oral exposure.