Clinical trials

Molecular imaging with myocardial contrast echocardiography (MCE) relies on the non-invasive detection of targeted microbubbles (MBs) or other acoustically active agents. The confinement of MBs to the vascular compartment makes them ideal for assessing acute inflammatory responses involving endothelial cell activation and immune cell recruitment. A construct for imaging inflammation and endothelial activation can be achieved by altering amphipathic lipid shell composition in MBs. Specifically, incorporation of phosphatidylserine (PS) into the shell of MBs promotes adhesion to activated leukocytes and endothelial cells which can be used to detect ischemia, whether active or resolved. Our first in human studies to use myocardial contrast echocardiography (MCE) to detect inflammation secondary to ischemia was performed with a PS-containing MB contrast agent (Sonazoid) where we studied patients with known acute coronary syndrome (ACS) who had just undergone acute percutaneous coronary intervention. In this study, we will conduct a proof-of-concept clinical trial where MCE molecular imaging with Sonazoid will be performed in 80 patients with suspected rather than known ACS. We will test whether MCE ischemic memory imaging with MB-PS can diagnose or exclude ACS, and assess risk based on spatial extent of signal enhancement.

Inflammation of the heart (myocarditis) is a serious condition that can cause heart failure, abnormal heart rhythms, cardiac arrest, and death. Rapid diagnosis of this condition is key to reversing it. The purpose of this study is to determine whether myocarditis such as that which occurs with viral illness, autoimmune conditions, or certain therapies (i.e. immune checkpoint inhibitors) can be diagnosed using a new form of ultrasound imaging of the heart (echocardiography) that uses a contrast agent that is targeted to inflammation (Sonazoid).

The purpose of this Phase IIa study is to identify the most effective antibiotic regimen to treat small intestine bacterial overgrowth (SIBO) in impoverished Bangladeshi children.

The purpose of this study is to investigate the efficacy of a positive affect enhancing intervention designed to reduce pain and augment reward system function in knee osteoarthritis (KOA) patients undergoing total knee arthroplasty (TKA). The scientific premise is that patient use of a positive emotion generative practice - savoring meditation, which has been demonstrated to reduce pain in experimental laboratory settings, enhanced with a pain neuroscience education component about reward system dysfunction as a chronic pain mechanism - is optimally suited to reduce postsurgical pain and augment reward system functioning relative to a Pain Self-Management and Education (PSME) condition. We will randomize 150 patients with KOA undergoing unilateral TKA to a brief, 4-session (20-30 minutes each) course of Savoring Meditation (SM; n = 75) or PSME (n = 75) delivered remotely by trained interventionists in a one-on-one format. We will assess pain and as well as pain-related risk and protective factors both via questionnaire and via weeklong ecological momentary assessment (EMA) data bursts on the following schedule: baseline, post-surgery, and 3-month follow-up. In addition, participants will attend laboratory testing sessions at baseline and 6-weeks post-surgery, during which affective pain modulation and electroencephalographic (EEG) brain biomarkers associated with pain and affect will be recorded. Participants in SM be encouraged to practice their savoring for 5 minutes/day during the week following surgery, as well as to use it to manage pain flares in a self-directed manner.

The primary objective of this study is to examine whether exercise training alone, liraglutide treatment alone or exercise training plus liraglutide treatment increases cardiac and muscle capillary blood volume, improves vascular function in the larger conduit vessels, and enhances insulin's metabolic action in humans with Type 2 diabetes. Subjects will be randomized to one of the three groups: exercise training, liraglutide treatment, and exercise + liraglutide. They will be studied at the baseline and then after 16 weeks of intervention.

This study seeks to develop improved cardiac MRI (CMR) methods to quantify epicardial adipose tissue (EAT) composition and to demonstrate the advantages of EAT composition imaging (a) in advancing the understanding of the relationship between EAT and heart failure with preserved ejection fraction (HFpEF) and (b) for understanding mechanisms of and guiding medical therapy in HFpEF. The investigators recently developed the first method for quantifying EAT FAC in human subjects, utilizing a rate-6 accelerated radial 2D multi-echo gradient-echo breathhold acquisition with a local low rank reconstruction. In this project the first specific aim is to develop a rapid free-breathing 3D EAT FAC MRI method that reduces motion-related artifacts, increases coverage, and facilitates higher spatial resolution and improved FAC reproducibility. The second specific aim is to show that EAT FAC is more strongly associated than EAT volume with cardiometabolic HFpEF. In this context, individuals with known or suspected HFpEF will undergo CMR, echocardiography, and other testing to (a) diagnose cardiometabolic HFpEF; (b) characterize features associated with the severity of HFpEF; and (c) assess EAT volume and FAC. The investigators will determine if EAT FAC is more strongly associated than EAT volume with HFpEF and with features associated with the severity of HFpEF. The third specific aim is to show, in the context of cardiometabolic HFpEF and pre-HFpEF, (a) that GLP-1 receptor agonism with semaglutide (SEMA) shifts the EAT FAC to a less proinflammatory profile and (b) that baseline EAT FAC is a stronger predictor than EAT volume of improved cardiovascular function due to SEMA. Cardiometabolic HFpEF and pre-HFpEF subjects will undergo echocardiography and CMR with EAT FAC at baseline and after 3 months to serve as a self-control. Subjects will then undergo repeat imaging 6 months after the initiation of SEMA. The change in FAC after treatment with SEMA will be compared to the change in FAC prior to SEMA. Data will be analyzed to show that SEMA changes EAT FAC, and that baseline EAT FAC is a stronger predictor than EAT volume of improvements in severity of HFpEF.

This cluster randomized trial aims to learn about the effectiveness of task-sharing supported by an epilepsy medical records system (EMRS) (hereafter referred to as BEACON) with patient-tracking data in improving treatment adherence and retention in care in people with epilepsy in western Kenya.

Co-occurring symptoms of insomnia and depression is very common in breast cancer survivors, and it is critical that scalable and easily accessible digital behavioral interventions are made available. Digital health interventions are scalable and accessible. Moreover, behavioral digital interventions have been shown to be effective in reducing symptoms of insomnia and depression, respectively, in breast cancer survivors, suggesting strong potential for public impact, though their potential for addressing co-occurring symptoms of insomnia/depression has not been tested. The purpose of this study is to evaluate the efficacy of a digital insomnia program and a digital mental health program in multiple ways: 1) as standalone interventions to reduce both symptoms of co-occurring insomnia and depression for breast cancer survivors; and 2) as components in adaptive behavioral treatment strategies that optimally sequence them for survivors who need additional support, resulting in a multifaceted supportive approach that is low cost, easily accessible, and highly efficient.

This is a feasibility study to determine whether pulsed ultrasound stimulation targeting the splenic nerve or the cervical vagus nerve can elicit an anti-inflammatory immune response in healthy volunteers.

The purpose of this study is to assess whether the natural form of estrogen (17-beta estradiol) given as a patch so that it is absorbed through your skin, is better at improving bone strength over 1 year than natural estrogen (17-beta estradiol) taken by mouth, or a synthetic form oestrogen (ethinyl estradiol) given as a patch that also provides birth control. Participants will: 1. Take estrogen for 1 year either (i) in its natural form as a patch twice a week (and progesterone by mouth for 12 days of each month), or (ii) in its natural form as a pill daily (and progesterone by mouth for 12 days of each month), or (iii) in a synthetic form as a birth control patch weekly for 3 weeks with 1 week off the patch. You will not be able to choose which form of estrogen you will receive as this will be assigned to you based on a pre-existing randomization sequence (like the flip of a coin) 2. Take provided calcium and vitamin D supplements 3. Attend 4 study visits over 12 months with two at the beginning and then every 6 months that include: * History and Physical Exams * Lab Work * Imaging studies * Questionnaires * Dietary recalls

Menopause greatly increases cardiovascular disease risk (CVD). Current exercise guidelines are inadequate to ameliorate this risk and higher intensity exercise may be necessary for cardiovascular benefits in postmenopausal females. Oral nitrate supplementation enhances exercise performance and CVD risk profile in several clinical conditions. The investigators recently reported that 3-days of nitrate supplementation in postmenopausal females enhances acute post-exercise vascular function, in an intensity dependent manner. The effects of nitrate supplementation and exercise training over a longer training program remains unexplored. This investigation will examine the impact of exercise training intensity with and without inorganic nitrate supplementation, on CVD and fitness outcomes. Postmenopausal females will be tested for maximal oxygen uptake and lactate threshold before randomization to one of four groups: that inorganic nitrate-rich beetroot juice, or beetroot juice with nitrate extracted; and assigned to one-month of calorie matched high-intensity or moderate-intensity exercise training. Vascular function and fitness will be evaluated before and after training.

This study uses a factorial optimization experiment to identify which treatment components help adults who smoke and are not ready to quit in the next 30 days (smokers not ready to quit, or SNRTQ) achieve smoking cessation. Participants are recruited through Federally Qualified Health Centers (FQHCs) in Virginia and West Virginia. All participants receive at least 8 weeks of nicotine replacement therapy (NRT) patch. Using a 2×2×2×2 factorial design, the study independently tests four components: a pharmacist-delivered behavioral program (VergeRx), a text-message support program (SmokefreeTXT), the addition of an NRT lozenge to the patch, and an extended 16-week course of the NRT patch versus the standard 8 weeks. The goal is to estimate the effect of each component on biochemically confirmed smoking abstinence so that an optimized treatment package can be assembled. The primary outcome is abstinence at 26 weeks; a secondary outcome is abstinence at 52 weeks.

Coal miners in Central Appalachia have among the highest rates of tobacco and nicotine product (TNP) use of any occupational group and face elevated rates of lung cancer and coal workers' pneumoconiosis ("black lung"). This study tests a novel medical-legal partnership (MLP) that "flips" the traditional referral direction: lawyers representing coal miners in black-lung workers' compensation cases identify clients who use TNPs and, through an ask-advise-connect process, connect them to community pharmacists who deliver QuitAid, a pharmacist-delivered medication therapy management (MTM) program, together with nicotine replacement therapy (NRT). The study has two aims: (1) an implementation-science evaluation of the ask-advise-connect process in black-lung law offices, and (2) a randomized feasibility pilot in which coal miners who use TNPs are randomized to receive QuitAid or not, with all participants receiving 24 weeks of NRT. As a feasibility pilot, the study is designed to estimate recruitment, randomization, retention, fidelity, and dose parameters to inform a future NCI R01, and is not powered to detect differences between conditions.

This is a Phase III, multisite exploratory study for women ≥ 65 years of age with early stage estrogen receptor positive (ER+) breast cancer. These individuals will be treated randomly assigned to one of two groups: Intervention, treated with 3 months of pre-operative endocrine therapy (pre-ET) OR Control, participants follow standard of care and proceed directly to breast cancer surgery. Both arms will be assessed for tolerance and compliance to the endocrine therapy by patient reported outcome (PRO) measures (patient surveys).

Digital mental and behavioral health interventions have potential to significantly improve accessibility for the large number of breast cancer survivors who need treatments. However, the landscape of digital interventions tested in this population remains limited, with the few that have been tested primarily focused on reducing symptoms of mental disorders. This is problematic given the range of psychosocial needs among breast cancer survivors, including those who may not have active mental health symptoms, yet could benefit from learning effective coping skills. Digital health interventions delivered through smartphones have strong potential to improve access to care for the large number of breast cancer survivors who need mental and behavioral health support. There is a need to evaluate a range of supportive interventions that target different aspects of mental health, including negative thinking, coping skills, and knowledge. Our research team has previously tested individual digital interventions in relatively small samples, and found that they were effective in reducing mood symptoms among women with breast cancer. The ultimate goal of this project is to evaluate how integrating these interventions into a single 8-week long app program affects mood and overall mental health in breast cancer survivors. The digital micro-interventions to be tested in this study are brief interventions that target specific behavioral and cognitive mechanisms of mental health. These include skills such as reducing negative thinking patterns, increasing knowledge of mental health factors, fostering a grateful outlook, promoting the practice of relaxation breathing, savoring positive memories, and acceptance-based mindfulness approaches.

The purpose of this study is to identify the best combination of new intervention components to use with CARRII, the first automated online intervention for alcohol-exposed pregnancies (AEP). This intervention is specifically designed for Native women and others who can become pregnant. Our goal is to maximize the effectiveness of the online intervention while keeping costs manageable for Native communities.

The primary purpose of this study is to explore the feasibility of conducting a clinical trial on the effects of psilocybin for individuals with prolonged grief disorder (PGD).

The purpose of this study is to understand the safety and estimate the efficacy of combining anti-cluster of differentiation 3 (CD3) x anti-Epidermal Growth Factor Receptor (EGFR) bispecific antibody fresh peripheral blood mononuclear cells (EGFR FPBMC) for patients with metastatic or unresectable pancreas cancer. Participants receive 8 twice weekly doses and then 8 more doses every 2 weeks of EGFR FPBMC by intravenous infusion.

This research study is testing a decision aid to help patients think through whether to have sentinel lymph node biopsy for melanoma. Sentinel lymph node biopsy (SLNB) can be a difficult decision for some patients because the potential benefits and risks may not be clear. This study is being done to learn whether providing structured, easy-to-understand information helps patients feel more informed and less uncertain about their decision. Patients in this study will be given a paper decision aid (DA). Patients will be given other short questionnaires to complete before and after the decision aid.

Binge drinking, and its health/social consequences are substantial public health concerns, with a high prevalence in young adults, especially in the US military. Alcohol consumption in the military is very high and normative, but there is zero tolerance for alcohol-related legal trouble, and Air Force Airmen who experience this (e.g., DUI, sexual assault) typically receive a disciplinary action referred to as an Alcohol Related Incident (ARI). Brief Alcohol Interventions (BAIs) for alcohol misuse are effective in young adults who report binge drinking. Many BAI studies targeted young adults who drink hazardously; these individuals are typically not interested in abstaining but may try decreasing the amount or change the manner in which they drink in order to reduce harmful consequences. The investigators previously published the results of a BAI group-based intervention that reduced ARIs in over 150,000 Airmen on average by 16%. Since 2010, the BAI has been disseminated to most USAF Airmen in Technical Training. However, it is clear additional research is needed to enhance the efficacy of the intervention and reduce risks associated with problem drinking. One strategy to improve health outcomes is well-timed, tailored, and automated text messages. Building on the researchers' preliminary study where text messages reduced driving after drinking as well as total drinks consumed before driving, text messaging may be highly effective when sent at the precise time that Airmen gain access to alcohol (the first time they are allowed off base), a standard time for all Technical Trainees. One challenge to conducting alcohol research in the military is the lack of privileged communication. As a result, it is difficult to obtain valid self-reports due to a tendency to deny or minimize use. The investigators recently developed and validated a method for collecting anonymous data over time. This will be the first study in the military, as well as the first large scale, adequately powered trial, where intervention effects will be tracked out to a 6-month follow-up. The study's Specific Aims are to randomize approximately 7000 Airmen to either the current BAI versus the BAI+Text messages timed to occur before, during, and after Airmen have access to alcohol; and to evaluate the efficacy of the intervention at the end of training and 6 months post-training using repeated surveys with unique identifiers allowing researchers to match surveys while maintaining anonymity.

The purpose of this study is to understand the safety and estimate the efficacy of anti-CD3 x anti-HER2 bispecific antibody (HER2Bi) armed fresh peripheral blood mononuclear cells (HER2 FPBMC) for patients with metastatic breast or prostate cancer. Participants receive 5 weekly doses of CD33 FPBMC by intravenous infusion followed by 4 infusions every other week.

The purpose of this study is to find out if patients with prostate cancer who have vasomotor symptoms, commonly called hot flashes, from their Androgen Deprivation Therapy (ADT) will consistently wear a smartwatch device to track their health data, log hot flashes on their smartwatch, and how these data compare with daily surveys about their hot flashes. Participants will be asked to wear the smartwatch for 4 weeks and to log their hot flashes on their smart watch pressing a button on the watch. Participants will be asked to complete surveys (sent through a text message link) to describe their experiences with hot flashes.

Proximal humerus fractures can be a debilitating injury in the elderly, impacting the ability to function independently or complete activities of daily living due to pain and restricted shoulder motion. Evidence has shown that reverse total shoulder arthroplasty (rTSA) is an effective option to improve pain and function for patients with acute displaced proximal humerus fractures. Given that patients undergoing rTSA for proximal humerus fractures typically experience worse functional outcomes, worse patient-reported outcomes, and higher rates of complication compared to those with elective indications for surgical intervention, it is critical to determine a secure path to recovery for these patients after surgery. Early rehabilitation has been proposed to be safe and effective for patients who undergo rTSA for elective indications; however, there is a paucity of research evaluating safety and effectiveness of timing of rehabilitation for rTSA patients in the trauma setting. Currently, there exists a great variability in postoperative rehabilitation protocols across orthopaedic practices. This study's objective is to determine the safety and effectiveness of early postoperative rehabilitation on the outcomes and postoperative complications of patients undergoing rTSA for proximal humerus fractures in order to provide more specific recommendations for this patient population.

The aim of this study is to compare standard post operative rehabilitation with a simplified wooden block stretching protocol that will yield similar results.

This study is examining whether short-term supplementation with inorganic nitrate, in the form of beetroot juice, can enhance blood vessel health, insulin sensitivity, and exercise capacity in individuals with prediabetes. We will be comparing the responses in individuals who are taking metformin to those who are naive to metformin. The results from this study may help identify non-pharmacological interventions in prediabetes.