Clinical trials

The objective of this study is to find a more objective and accurate way to assess the efficacy of the treatment for neurogenic orthostatic hypotension. For this purpose, the investigators will use an activity monitor to determine the amount of time patients spend in the upright position (standing and walking; upright time) during 1 week of placebo (a pill with no active ingredients) and 1 week of their regular medication for orthostatic hypotension (midodrine or atomoxetine at their usual doses). Total upright time (i.e. tolerance to standing and walking) will be compared between placebo and active treatment to test the hypothesis that it can be used to assess the efficacy of the treatment for orthostatic hypotension and whether this outcome is superior to the assessment of symptoms using validated questionnaires.

Dystrophin associated heart dysfunction is a leading cause of death in patients with Duchenne and Becker Muscular dystrophy (DMD/BMD) and Duchenne and Becker muscular dystrophy carriers (MDC); however, the evolution of heart dysfunction is not well-understood. The central objectives of this proposal are to elucidate this evolution of heart dysfunction and identify measures from cardiac MRI images that can predict death or significant heart disease in patients with DMD/BMD/MDC. This study will create a large clinical and cardiac MRI registry of dystrophin associated heart dysfunction, will utilize advanced image analysis techniques, including deep learning neural networks, to comprehensively evaluate every patient, and will create a risk toolkit accessible to clinicians around the world; this proposal has the potential to improve the quality of life in patients with dystrophin associated heart dysfunction by allowing for earlier and more intensive therapy in patients with severe disease and by identifying surrogate outcome measures for use in therapeutic trials.

The rationale is that only through understanding how individual Cochlear Implant (CI) patients respond to interventions investigators further develop precision-medicine approaches to optimize outcomes. In the proposed research study to investigate the hypotheses, investigators will address two Specific Aims: Specific Aim #1: Define the auditory (bottom-up), cognitive-linguistic (top-down), and functional neuroimaging profiles of adult CI users. Investigators will enroll experienced CI users (\> 6 months of CI use). Specific Aim #2: Determine the feasibility of "auditory" (bottom-up) and "cognitive" (top-down) interventions to improve speech processing in adult CI users. The main hypothesis is that the two interventions are feasible. Investigators also hypothesize that our study protocol will detect the variance in auditory processing profiles and that investigators will show promise in improving both speech processing (using speech recognition and Functional Near-Infrared Spectroscopy (fNIRS) responses)) and real-world functioning (using patient-reported measures), compared with no intervention. Additional hypotheses to be explored are that baseline profile (as defined in Aim #1) will impact the magnitude of participants' responses to the interventions, as will order of interventions (Auditory-Cognitive vs. Cognitive-Auditory, AC vs CA).

Polysomnography (PSG) and drug-induced sleep endoscopy (DISE) are widely used diagnostic studies for assessing obstructive sleep apnea (OSA) severity and collapse patterns of the upper airway anatomy during sleep. Hypoglossal nerve stimulation (HNS) therapy for obstructive sleep apnea suffers from variable response at the level of the soft palate. The Investigators propose a study examining the physiologic effect of ansa cervicalis stimulation (ACS) alone and in combination with HNS during PSG and DISE.

Progressive age-related cognitive deficits occurring in both AD and DS have been connected to the degeneration of several neuronal populations, but mechanisms are not fully elucidated. The most consistent neuronal losses throughout the progression of AD are seen in cholinergic neurons where these losses negatively affect cognition, particularly in attention, learning, and memory formation. Evidence of reduced cholinergic integrity in DS is largely limited to animal models and post-mortem human data. The investigators propose to use molecular, functional, and structural biomarkers to assess the cholinergic integrity in adults with DS. The investigators anticipate using the data gathered in this pilot study to inform future study designs to determine AD risk stratification in DS by identifying individuals who show an accelerated decline in cholinergic integrity that correlates with cognitive and neurobehavioral changes. Also, our cholinergic biomarkers may identify whether individuals with DS are likely to respond to pro-cholinergic interventions, including the novel cholinergic modulators that are being developed to enhance cholinergic-sensitive cognitive functioning. The investigators anticipate using the data gathered here to inform future treatment studies in TRC-DS and beyond where novel cholinergic treatments may offer opportunities for early intervention in DS and be complementary to disease-modifying approaches such as anti-amyloid treatments.

Cirrhotic Cardiomyopathy (CCM) is a recognized complication of cirrhosis, but understudied despite recent retrospective data suggesting it may be common, affecting one in three patients with decompensated cirrhosis, and associated with significantly increased risk of death and adverse hepatic and cardiac events. Moreover, evidence from preclinical models and children suggest elevated bile acids in the blood may contribute to CCM, but data from adults with cirrhosis are scarce. Therefore, we are conducting the first contemporary prospective multi-center investigation of CCM in adults in the USA to define CCM risk factors and impact on outcomes while deepening understanding of the role of bile acids in development of this disease.

The study's objective is to conduct a Phase II randomized controlled trial examining the preliminary efficacy of the VoiceLove app compared to usual care on maternal postpartum depression in mothers with infants admitted to the Neonatal Intensive Care Unit (NICU). Primary aim: Assess the effects of VoiceLove on maternal postpartum depression, measured by the Edinburgh Postnatal Depression Scale (EPDS). The estimates from this study will be used for a future definitive Phase III trial. Secondary aim: Assess feasibility, acceptability, and patterns of communication and engagement among mothers, partners, and NICU clinicians during the NICU hospitalization, measured through app usage metrics, satisfaction surveys, and qualitative interviews. Additionally, we will evaluate effects of infant length of stay.

Based on existing literature and clinical trials, 2- hydroxbenzylamine (2-HOBA) has clear impact on mechanisms that much of the international field of pulmonary hypertension (PH) research agrees are central to disease progression. The investigator's preliminary data and Phase I studies demonstrate not only a clear positive impact on reducing pulmonary vascular resistances in Group I and II PH, and both cytokine and molecular biomarkers of disease, but also indicated the potential for a substantial positive effect on heart function under load stress. In this Phase II project, investigators will test the safety and efficacy of 2-HOBA in PH patients, improving the function of the right ventricle under stress in a large animal model, and effectiveness in the context of standard-of-care in mouse models and large animals, to establish the remaining data needed to proceed to commercialization.

Delirium is a common syndrome in intensive care unit (ICU) patients. Those experiencing delirium may suddenly feel confused, have trouble thinking clearly, struggle to pay attention, or see and hear things that are not real. Delirium is associated with worse long-term outcomes such as cognitive impairment, depression, and PTSD (post-traumatic stress disorder). This study examines whether an investigational medical-grade ketone supplement drink (ketone monoester \[brand name: Ultrapure Ketone Monoester\]) is safe and feasible to use in ICU patients, and to look for signals that it might reduce delirium or shorten its duration compared to a volume-, taste-, and calorie-matched placebo.

The goal of this study is to learn more about the brain activity underlying Parkinson's disease risk taking and reward seeking behaviors. The investigators will utilize neural recordings from corticostriatal structures performed during deep brain stimulation surgery to measure neural activity underlying nonmotor symptoms of Parkinson's disease.

This ClincialTrials.gov record originally corresponded to the protocol approved under IRB # 202370. The study was expanded to include stimulation and recordings approved under new IRB #211037. The participant data originally acquired from IRB# 202370 will be included in this new record: This study seeks to better understand the neural activity underlying neuro cognitive disorders. Resting state local field potential recordings will be collected from medically refractory epilepsy patients implanted with depth electrodes for seizure localization, and metrics of neural activity will be correlated with psychiatric symptoms as measured from questionnaires. Subjects will also participate in neuro cognitive tasks while neural recordings are performed, and/or receive neural stimulation through implanted depth electrodes. A better understanding of disordered neural activity underlying neuropsychiatric disorders may additionally contribute to novel methods for diagnosing, treating, and preventing these diseases.

The goal of this study is to learn more about the brain activity underlying Parkinson's disease cognitive impairment. The investigators will utilize neural recordings from corticostriatal structures performed during deep brain stimulation surgery to measure neural activity underlying nonmotor symptoms of Parkinson's disease.

This ClinicalTrials.gov entry corresponds to the Neural Basis of Human Working Memory protocol approved under Vanderbilt University Medical Center IRB #251231. This study investigates the neural activity underlying human working memory, via local field potential changes (macro level) and/or single neuronal spiking changes (micro level) from depth electrodes placed for invasive seizure monitoring. Subjects will complete neurocognitive tasks while neural recordings are collected. Some patients will complete neurocognitive tasks while stimulation is applied via depth electrodes. Further understanding the neural activity changes underlying normal and impaired working memory may help to identify novel diagnostic methods and treatments for impaired working memory and may support the use of stimulation for treatment of memory disorders.

Duchenne Muscular Dystrophy (DMD) is a rare, genetic disease that leads to muscle weakness, breathing difficulties, heart disease, and early death. Approximately half of individuals with DMD have elevated body mass indices (BMIs) in the overweight or obesity range. High BMI is due to a combination of factors including limited mobility and steroid medications, which are used to treat DMD. There are new medications, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) that promote weight loss in the general population. GLP-1 RAs are approved for weight loss in children and adults and have beneficial effects on the heart. There is a concern that these medications could have unwanted side effects in individuals with DMD, specifically decreasing their muscle mass. While it is important to consider the use weight-loss medications in DMD, the investigators want to ensure that they are safe and well-tolerated. Therefore, this study will systematically evaluate whether the use of GLP-1 RAs in adolescents and young adults with DMD affects muscle mass. The overall goal of this study is to assess the safety and tolerability of GLP1-RAs in individuals with both DMD and obesity. The primary focus will be on muscle health, but the study will also evaluate activity levels, mood, gastrointestinal symptoms, and quality of life. Secondary goals will be to understand the impact of GLP1-RAs on weight, fat mass, glucose and insulin levels, and heart and lung function in individuals with DMD. The investigators hypothesize that GLP1-RAs will be well-tolerated and will decrease fat mass, without a large decrease in muscle mass. Participants will: * Take oral semaglutide or a placebo every day for 24 weeks (randomized controlled trial) * Then take oral semaglutide every day for 40 weeks (open label extension) * Complete in-person study visits at 3 timepoints * Study visits may include: an MRI of the body to evaluate muscle and fat tissue, laboratory testing, a mixed meal tolerance test, questionnaires, an MRI of the heart, pulmonary function tests, and additional measures * Calls with the study team between visits (monthly or every other month)

The coronary arteries supply blood to the heart muscle. Typically, the left coronary artery comes from the left side of the aorta and the right coronary artery comes from the right side. In some cases the coronary artery comes from the wrong side of the aorta. This is known as anomalous aortic origin of a coronary artery (AAOCA). In AAOCA, the major concern is the risk of sudden cardiac death (SCD). The risk of is significantly higher in left AAOCA (L-AAOCA) compared to right AAOCA (R-AAOCA). With the increased risk in L-AAOCA, surgery is recommended to "normalize" the coronary artery position. R-AAOCA has a low absolute risk of SCD. But the risk is higher than the general population. Patients, families, and clinicians must weigh the risks of surgery with the risks of observation. This leads to stress and anxiety around making the management choice. There is no "right" management choice. Shared decision making (SDM) is a strategy of including patient values, preferences, and risk tolerance in medical choices. SDM is particularly useful in settings where there is no clear correct management choice. Decision aids support SDM. No decision aid exists in R-AAOCA. This proposal will create a decision aid and collect pilot data of its implementation. We hypothesize that the use of an aid in R-AAOCA will improve SDM, comfort in the choice, and quality of life. We will engage patients, families, and clinicians to understand their needs to make management choices. This will inform the development of the aid. We will gather feedback on the aid from stakeholders and will revise it. The aid will include data and methods for patients to identify their preferences. When the aid is optimized, we will run a pilot study to evaluate its impact compared to not using the aid. We will evaluate SDM, comfort in the choice made, and quality of life at that time, at 3 months and at 6 months. The pilot data will be used to inform a larger study of the aid. This proposal can be an example how to design decision aids for other congenital heart conditions. This aligns with the AHA's mission of improving lifelong health of the whole person. By improving SDM , patients can feel more confident in their choice and relieve anxiety from the diagnosis. Overall, this proposal supports a shift to patient-centered care with a focus on improving meaningful lifelong outcomes.

Anastomosis refers to the surgical connection between two segments of the bowel, typically performed during colon and rectal surgeries to restore the continuity of the digestive tract after a section has been removed. It is necessary that the ends of the tissue at the anastomotic site are healthy (and capable of healing properly) as this will prevent dreaded complications like anastomotic leaks or strictures which can occur in almost a fifth of patients leading to increased hospital length of stay, costs, and mortality. Currently, the most widely used method for assessing tissue viability during anastomosis is indocyanine green fluorescence angiography (ICG-FA). This technique involves injecting a fluorescent dye (indocyanine green) into the bloodstream, which highlights blood flow and tissue perfusion under a special camera. However, ICG-FA has limitations due to allergies and reliability due to the dye's rapid disappearance from the bloodstream. Additionally, the dye cannot be administered repeatedly. This study explores a new method of measuring tissue oxygenation by evaluating mucosal oxygen saturation (StO2) as an alternative to ICG-FA. By evaluating StO2 levels, the research aims to provide a more reliable and repeatable way to assess tissue viability without the drawbacks of using fluorescent dyes. Secondly, any blood supply interruption to the bowel will first lead to mucosal ischemia, which can potentially be reliably captured by measuring mucosal StO2 levels only. In this single-center prospective single-arm study, we will evaluate whether mucosal StO2 levels are associated with or can predict anastomotic complications. This study will not involve any intervention that would affect the standard of care.

This is a single center, pragmatic, randomized trial comparing the effectiveness of two commonly used approaches (co-treatment and individual treatment) in acute care rehabilitation.

This study will investigate the potential benefits of rose scent in reducing the risk of Sudden Unexpected Death in Epilepsy (SUDEP) in patients with epilepsy. Participants will engage in their routine inpatient observational EEG monitoring for 24 hours followed by an additional 24 hours of observational EEG monitoring with continuous exposure to rose scent, during which an essential oil diffusor with rose scent will be placed in their hospital room. During these 48 total hours of the study, participants will wear a respiratory monitoring belt across their upper chest to measure their breathing. Potential risks include distress or discomfort when smelling the rose scent used in the study, a physical reaction to the rose scent, and discomfort or feelings of restrictiveness when wearing the respiratory monitoring belt. The total time commitment of the study is 48 consecutive hours over the course of the participants' inpatient EMU stay, during which there will be no restrictions on daily activities during the standard inpatient EMU admission except that participants must wear their respiratory belt for a majority of this 2-day period.

This study will use an anticholinergic pharmacological probe to examine attention network function in SCD using EEG. The overall hypothesis is that in older adults with SCD, normal cognitive performance is maintained by compensatory attention network activity, supported by enhanced cholinergic function. The investigators anticipate that SCD will be associated with greater compensatory attention network activity and that disrupting this compensatory process through anticholinergic challenge will result in a greater negative effect on attentional performance (Attention Network Test, ANT) and attention network functioning (EEG) in older adults with greater subjective cognitive concern.

Traumatic pneumothorax and hemothorax are common consequences of chest injury, often requiring prompt tube thoracostomy to re-expand the lung and drain accumulated blood or air. Current practice varies widely regarding whether chest tubes should initially be placed to suction or to water seal, and prior studies have reported mixed findings. While suction may theoretically improve drainage and lung expansion, some studies suggest it may prolong air leaks and chest tube duration. Conversely, initial water seal has been associated with shorter tube duration without an increase in complications. The predecessor to this trial, the SEAL IT Trial, demonstrated that water seal reduced chest tube duration in patients with pneumothorax without an increase in complication, but excluded those with significant hemothorax. This single-center, randomized controlled trial (SUS-HPTX) will expand upon those findings by evaluating the effect of initial chest tube management strategy, suction versus water seal, in trauma patients with hemopneumothorax or hemothorax. Patients will be assigned to one of the two groups based on calendar month of enrollment, with clinicians able to adjust management as needed. The primary outcome is chest tube duration. Secondary outcomes include chest tube-related complications (e.g., empyema, pneumonia, re-accumulation of pneumothorax or hemothorax, need for additional procedures), hospital length of stay, readmissions, and mortality. Because both suction and water seal are accepted standards of care, the study involves minimal incremental risk. Findings will expand prior evidence and inform best practices for chest tube management in trauma

The central hypothesis is this: Brain circuits most relevant to cannabis use in schizophrenia are distinct from pathways identified in healthy controls who use cannabis. This study seeks to provide evidence that targeted stimulation of the DMN leads to both altered network activity and a concomitant behavioral change in cue-induced craving and cognitive performance in individuals with schizophrenia and schizoaffective disorder, while targeted stimulation of the L DLPFC leads to these changes in healthy controls who use cannabis. This study will test a model that integrates brain network pathophysiology and cognition to 1) explain the prevalence of cannabis use in schizophrenia and 2) identify a target for engagement in schizophrenia. This study seeks to establish a neuroscientific framework to guide future treatment-oriented studies aimed at reducing craving and improving cognitive performance in individuals with schizophrenia and schizoaffective disorder. This is a study of the effect of 2 rTMS interventions on functional connectivity and craving in individuals with schizophrenia or schizoaffective disorder and healthy controls who use cannabis. Aim 1: Target Engagement: Determine if rTMS manipulates functional connectivity of each target (DMN, L DLPFC) (n=100). Aim 2: Clinical Efficacy: Determine if rTMS affects cue-induced craving and if craving change correlates with change in functional connectivity (n=100). As an exploratory analysis, the factors that explain individual variance in rTMS-induced connectivity change will also be explored.

The main goal of this clinical trial is to understand the benefits of remotely delivered Empowered Relief in patients undergoing lumbar spine surgery. The main question the trial aims to answer is: Does a postoperative behavioral intervention, Empowered Relief, performed early after back surgery have a measurable impact on postoperative outcomes? Additional questions are whether changes in pain catastrophizing are related to improvements in outcomes and whether preoperative pain catastrophizing is a moderator of response to treatment. Researchers will compare remotely delivered Empowered Relief to remotely delivered education to see if Empowered Relief helps patients manage their pain and functional limitations after back surgery. Participants will: * Complete one group session of remotely delivered Empowered Relief or Education after back surgery * Complete surveys before surgery and 3- and 6-months after surgery

The investigators propose to study the relationship between right ventricle (RV) steatosis and RV function, exercise capacity, and outcomes in humans with pulmonary arterial hypertension (PAH) and to identify potential drivers of lipid accumulation.

The primary aim of this study is to evaluate the feasibility of single-port robotic surgery for DIEP flap breast reconstruction. The investigators will also investigate complications of the procedure, incision length, flap success rate, post operative pain, vascular pedicle length and caliber, and VMP-B score (quality of life/satisfaction of breast procedures survey).

This is a clinical trial to determine the extent to which ultrasound-assisted lumbar puncture using a standardized procedure, including use of ultrasound to ascertain the presence of cerebrospinal fluid (CSF) at L3 - L5 and the optimal needle insertion distance, increases the acquisition rate of CSF that is interpretable for patient management.