Establishing Reference Values and Clinical Decision Points for Videofluoroscopic Measures of Swallowing
7/28/2022 – 7/30/2027
Dysphagia (swallowing impairment) is a serious health condition seen in many age-related disease and injury processes. Although videofluoroscopy (VF) is an international “gold standard” dysphagia diagnostic exam, there is a paucity of available normative physiologic VF reference values in healthy adults across the age span to guide interpretation of this examination. This fundamental gap in knowledge contributes to poor agreement in the identification of swallowing impairment and its underlying mechanisms. To enable better dysphagia diagnostics, there is a critical need to establish reference values for VF swallowing measures across the healthy age span. In our previous R01 (DC011020), we developed a rigorous method for measuring swallowing physiology from VF: the Analysis of Swallowing Physiology: Events, Kinematics and Timing (ASPEKT Method). We published initial ASPEKT reference values from 40 young healthy adults (<60 years) and performed preliminary analyses to compare data from healthy older adults and small cohorts of adults with dysphagia to these reference data. Through this renewal application, we will validate the ASPEKT Method healthy reference values for swallowing across the adult life span, demonstrate scalability of the ASPEKT Method across commonly used variations in clinical VF testing protocols, and profile swallowing pathophysiology in clinical groups where dysphagia is a cause of morbidity to identify clinical decision points that can be used for diagnosis and outcome measurement. Our vision is that the ASPEKT Method will enable clinicians to compare patient measures to healthy reference values, facilitating quantification and evidence-based interpretation of the presence, nature and severity of swallowing impairment. Ultimately, we seek to generate data that will shift subjective dysphagia diagnostic practices toward a quantitative, evidence-based diagnostic framework that will improve resource utilization, treatment planning and patient outcomes.
Mechanisms, Predictors and Clinical Markers of Dysphagia in Cardiac Surgical Patients
4/2022 – 3/2027
Dysphagia (swallowing impairment) is a common complication of cardiac surgical procedures, leading to malnutrition, dehydration, aspiration pneumonia, reintubation, increased health care utilization, length of hospitalization, and economic burden. We will enroll 360 cardiac surgical patients over a four-year period and identify 1) independent risk factors for dysphagia, 2) sensitive clinical markers of swallowing impairment, and 3) governing physiologic mechanisms of unsafe and inefficient swallowing throughout the acute, sub-acute, and long-term postoperative period. Enrolled participants will undergo a preoperative Fiberoptic Endoscopic Evaluation of Swallowing (FEES) to screen out patients with pre-existing dysphagia. Candidate predictor variables will be systematically collected throughout the perioperative time course. Following surgery and within 48 hours of extubation, a simultaneous videofluoroscopy and FEES (VF-FEES) will be performed as well as a battery of simple bedside clinical tests. Detailed blinded analyses will be performed using validated metrics of swallowing safety, efficiency, timing and kinematics to examine acute-phase swallowing function and associated physiologic mechanisms of unsafe or inefficient deglutition. Patients with acute postoperative phase dysphagia will be re-examined at one- and six-months to determine sub-acute and long-term dysphagia trajectories and governing mechanisms of impairment and recovery. Multivariable modeling of dysphagia risk factors will produce a practical dysphagia risk stratification tool to enable accurate forecasting and personalized triaged postoperative care pathways. An accompanying open-access electronic application will be developed to provide seamless clinical adoption and a data-driven clinical decision making tool. The discriminant ability of clinical markers will be determined, and a practical bedside dysphagia screening tool validated to enable accurate detection and monitoring of dysphagia in the cardiac intensive care unit.
Delineating Physiologic Mechanisms of Swallowing impairment and Decline in Amyotrophic Lateral Sclerosis
4/2017 – 3/2023
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease causing progressive muscle weakness and impairments in swallowing (dysphagia) leading to malnutrition, dehydration, aspiration pneumonia, and ultimately death. The purpose of this research study is to understand the natural appearance and progression of swallowing impairment throughout disease progression and to identify a set of sensitive, easy to administer clinical tests that can accurately detect swallowing impairment for easy implementation into ALS clinics. This work will produce a highly practical and conceptually novel dysphagia risk index tool (PRISIM). 110 individuals with a diagnosis of ALS will complete a comprehensive evaluation of speech, breathing, swallowing and cough function every three months in the ARC laboratory at the University of Florida. Information derived from this study will produce the first natural history model of bulbar decline for swallowing function in ALS. This study is funded by the National Institutes of Health Division of Neurologic Disorders and Strokes (NINDS).
Landis Award for Outstanding Mentorship
This NINDS supplement was awarded to Dr. Plowman for her excellence in mentorship and is a training grant to support the education and development of her students and fellows.
Dysphagia in Congenital Heart Disease
Childrens Miracle Network
This pilot award supports a new collaboration with Dr. Mark Bleiweis to investigate mechanisms of swallowing impairment and failure to thrive in neonates and infants undergoing cardiac surgical procedures.
Safety & Therapeutic Potential of Metformin for C9orf72 ALS
9/1/2022 – 8/31/2024 ($500,000)
A G4C2 repeat expansion in C9ORF72 is known to be the most common cause of familial and sporadic amyotrophic lateral sclerosis. While there are currently no effective treatment strategies for ALS, reducing the levels of toxic proteins produced by repeat associated non-AUG (RAN) translation has been shown to improve disease phenotypes in a number of preclinical models. Our team has shown that metformin, a well-tolerated type-2 diabetes drug, inhibits a key pathway important for RAN translation in preclinical studies. Metformin-treated C9-BAC transgenic mice showed decreased RAN protein levels, improved behavior, and increased motor neuron survival (Zu et al., PNAS 2020). To test the safety and potential efficacy of metformin in C9orf72 ALS patients, this open label Phase 2 clinical trial will test if metformin reduces RAN proteins and is safe in C9orf72 ALS patients. Molecular, functional and imaging studies will be used to identify biomarkers for a larger multi-site placebo-controlled trial. If successful, repurposing metformin would provide a low-cost treatment that is available to treat the most common genetic form of ALS
Impact of Nuedexta on Swallowing, Speech and Cough Physiology in ALS
ALS Association Clinical Management Grant
Speech and swallowing difficulties occur throughout disease progression in individuals with ALS who rate this symptoms as the worst aspect of the disease (Hillel and Miller, 1989). These impairments lead to social isolation and withdrawal, reduced quality of life and mental wellbeing, malnutrition, aspiration pneumonia and death. A current gap in the clinical care of individuals with ALS is effective treatments to either improve or maintain speech and swallowing function. An exciting and promising drug that is already approved by the FDA for use in ALS patients, Nuedexta, was recently documented to improve patient-rated speech and swallowing function (Smith et al., 2016). While this is very promising, no study has yet determinte the impact this pharmacologic intervention has on objective clinical and physiologic outcomes of speech and swallowing in ALS patients. The primary goal of this proposal is to rigorously evaluate the impact of a pharmacological treatment, Nuedexta, on swallowing physiology, airway protection and speech intelligibility in individuals with ALS. Outcomes of this work will provide valuable physiologic insight into a promising therapeutic and help to reduce current gaps in the clinical management of individuals with ALS.
Physiological Flow of Liquids Used in Dysphagia Management
The practice of thickening liquids has become one of the most frequently used interventions for swallowing impairment (dysphagia). Surprisingly however, it is not yet established how this intervention impacts swallowing physiology and bolus flow. This study will examine the impact of liquid rheology or viscosity on bolus physiological flow during swallowing. The ARC laboratory will specifically focus on swallowing outcomes in neurodegenerative diseases and will include individuals with ALS (enrollment completed) and Parkinson’s disease (currently enrolling). Enrolled participants will attend the ARC laboratory at the University of Florida one time and undergo a videofluoroscopic swallowing evaluation. This study is funded by the National Institute on Deafness and Other Communication Disorder.
Lung Volume Recruitment Therapy with Expiratory Muscle Strength Training in ALS
ALS Association Clinical Management Grant
Dysphagia, dystussia (cough impairment), and respiratory impairment are hallmark features of ALS. Recent evidence by Dr. Plowman suggests that mild to moderate intensity respiratory exercises applied early in the disease progression can improve and maintain these vital functions. The study is being directed in conjunction with Co-Principal Investigator David Walk, and the purpose of this study is to investigate the effects of two treatment techniques, Expiratory Muscle Strength Training (EMST) and Lung Volume Recruitment (LVR), on breathing, swallowing, speech, and cough function in early affected individuals with ALS. Previous work by Dr. Plowman indicated EMST to be an effective treatment method for improving cough function and swallowing in ALS. LVR is a technique performed with a resuscitation bag fitted with a mouthpiece and a one-way valve to increase cough function and passive expansion of the lungs. In this randomized control trial in partnership with the University of Minnesota, participants are assigned to one of two treatment groups- EMST intervention alone or combined treatment of EMST and LVR. This study is funded by the Amyotrophic Lateral Sclerosis Association.
Examining the therapeutic potential of an FDA-approved drug Metformin for C9orf72 ALS/FTD
UF Moonshot PIlot Grant
Metformin is an FDA approved drug used with a diet and exercise to control high blood sugar in adults with type II diabetes. Preclinical studies conducted by Dr. Laura Ranum at the University of Florida demonstrate that Metformin may improve C9orf72 ALS symptoms in a transgenic mouse model. This study aims to determine if Metformin is a safe and potentially viable therapeutic treatment for individuals with C9orf72 ALS. This open-label study is funded by the Center for NeuroGenetics in the College of Medicine at the University of Florida and the University of Florida Moonshot Neuromuscular Health Initiative. We are recruiting individuals with a confirmed C9orf72 ALS diagnosis who will be studied over a one year period.
Improving Detection and Clinical Care of Dysphagia in Cardiac Surgical Patients
UF Department of Surgery Pilot Grant
Dysphagia is a common complication following cardiac surgery leading to delayed return to oral intake, increased risk of dehydration and malnutrition, intubation, and death. Dysphagia- linked aspiration pneumonia is a potentially preventable condition and is the leading cause of mortality following open heart surgery. While dysphagia is a known complication of cardiac procedures, little is known regarding potential demographic, clinical, or surgical factors that place a patient at higher risk for developing dysphagia. In addition, our preliminary data shows that nurses lack sufficient training in performing swallowing screens and lack sensitive screening tools to detect dysphagia. Therefore, this study aims to (1) identify risk factors for postoperative dysphagia and create a clinically useful online dysphagia risk stratification tool (CRISM-C), (2) identify a set of sensitive and easy to administer bedside markers of dysphagia to develop and validate a nursing screening tool, and (3) development of an educational nursing learning platform. This study is being conducted with ARC collaborator Dr. Eric Jeng and is sponsored by the Departments of: Speech, Language and Hearing Science and Thoracic and Cardiovascular Surgery at University of Florida.
Upper Airway Sensory Degradation in Individuals with ALS
Clinical and Translational Science Institute (CTSI) Pilot Grant
Amyotrophic Lateral Sclerosis Association Clinical Management Grant
Impact of Respiratory Training in Amyotrophic Lateral Sclerosis
National Institute of Child Health Development
R21 HDO75327 Effects of Strength Training on Bulbar Function in Persons with Amyotrophic Lateral Sclerosis
National Institute of Deafness and Other Communication Disorders
R03 DC012123 Dissociating the Neural Substrates of Cranial & Limb Motor Impairment in an Animal Model of PD
National Institute of Deafness and other Communication Disorders
F32 DC010569 Ruth L. Kirschstein National Research Service Award F32 Individual Post-Doctoral Fellowship
Neural Substrates of Oral Motor Dysfunction in Parkinson’s Disease
Veterans Affair Office of Rural Health
N08-FY14Q4-S0-P01503 Reducing Barriers to living at home for the Rural Veteran with Amyotrophic Lateral Sclerosis
University of South Florida College of Medicine Interdisciplinary Seed Grant
IS415-3 Impact of Lingual Resistance Exercise Training on Swallowing Function, Airway Protection and Oral Intake in Neurodegenerative Disease
University of South Florida Research and Innovation Grant
Impact of Exercise on Disease Progression and Survival in a Transgenic Mouse Model of ALS
Joy McCann Center for Swallowing Disorders Research Foundation
Impact of EMST on Bulbar Function in Amyotrophic Lateral Sclerosis: A Pilot Study
Ruth L. Kirschstein National Research Service Award T32 Institutional Training Fellowship
National Institute of Deafness and other Communication Disorders