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. ​

Recruitment, Screening and Retention of Panelists Who Wear Mandibular Partial Dentures​

Principal Investigator: Dr. Domenick Zero, DDS, MS​

The Oral Health Research Institute (OHRI) of the Indiana University School of Dentistry has developed several intra-oral caries models for evaluating the efficacy of dental products. These studies require a panel of subjects who wear mandibular partial dentures. Subjects participating in these studies wear their own partial denture (or in some cases, lower partial dentures made for them) modified to hold human or bovine teeth specimens for a designated time and use study products as instructed. The tooth specimens (sterilized before placement into the lower partial denture) are analyzed in the laboratory following clinical exposure. ​

The primary objective of this proposal is to recruit and screen a panel of mandibular partial denture wearers who meet the general qualifications for future study participation. This screening process will be ongoing as natural attrition (loss of interest in study, moving, medical problems, age, etc.) is anticipated. Persons accepted into the panel will be contacted periodically to determine interest in participation in intra-oral studies. ​

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. ​

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.​​

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​

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. ​

This proposal is responsive to NIDCR’s 2021-2026 Strategic Plan Goals 2 [Develop more precise and individualized ways of managing and preventing oral and craniofacial diseases ] and 3 [Accelerate the translation of research and the uptake of new discoveries into oral and general healthcare practices that reduce health inequities and disparities and improve oral health outcomes for individuals and communities worldwide].​